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In biology, the word gene (from Greek : γένος, génos ; [1] meaning generation [2] or birth [1] or gender) can have several different meanings. The Mendelian gene is a basic unit of heredity and the molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and noncoding genes. [3] [4] [5] [6]


During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes (many different genes) as well as gene–environment interactions. Some genetic traits are instantly visible, such as eye color or the number of limbs, and some are not, such as blood type, the risk for specific diseases, or the thousands of basic biochemical processes that constitute life.

Genes can acquire mutations in their sequence, leading to different variants, known as alleles, in the population. These alleles encode slightly different versions of a gene, which may cause different phenotypical traits. Usage of the term "having a gene" (e.g., "good genes," "hair color gene") typically refers to containing a different allele of the same, shared gene. [7] Genes evolve due to natural selection / survival of the fittest and genetic drift of the alleles.

The concept of gene continues to be refined as new phenomena are discovered. [8] For example, regulatory regions of a gene can be far removed from its coding regions, and coding regions can be split into several exons. Some viruses store their genome in RNA instead of DNA and some gene products are functional non-coding RNAs. Therefore, a broad, modern working definition of a gene is any discrete locus of heritable, genomic sequence which affect an organism's traits by being expressed as a functional product or by regulation of gene expression. [9] [10]

The term gene was introduced by Danish botanist, plant physiologist and geneticist Wilhelm Johannsen in 1909. [11] It is inspired by the Ancient Greek: γόνος, gonos, that means offspring and procreation.

Conflicting definitions of 'gene'

There are lots of different ways to use the term "gene." Richard Dawkins, for example, wrote a book called "The Selfish Gene" [12] where 'gene' simply meant any part of the chromosome that was subject to natural selection. This 'gene' is often referred to as the "Mendelian gene" whereas the physical gene described in this article is called the "molecular gene." [3]

The very first edition of the textbook "Molecular Biology of the Gene" (1965) described two kinds of molecular gene: protein-coding genes and those that specified functional RNA molecules such as ribosomal RNA and tRNA (noncoding genes). [13] But the idea of two kinds of genes dates back to the late 1950s when Jacob and Monod speculated that regulatory genes might produce repressor RNAs. [14]

This idea of two kinds of genes is still part of the definition of a gene in most textbooks. For example,

"The primary function of the genome is to produce RNA molecules. Selected portions of the DNA nucleotide sequence are copied into a corresponding RNA nucleotide sequence, which either encodes a protein (if it is an mRNA) or forms a 'structural' RNA, such as a transfer RNA (tRNA) or ribosomal RNA (rRNA) molecule. Each region of the DNA helix that produces a functional RNA molecule constitutes a gene." [15]
"We define a gene as a DNA sequence that is transcribed. This definition includes genes that do not encode proteins (not all transcripts are messenger RNA). The definition normally excludes regions of the genome that control transcription but are not themselves transcribed. We will encounter some exceptions to our definition of a gene - surprisingly, there is no definition that is entirely satisfactory." [16]
"A gene is a DNA sequence that codes for a diffusible product. This product may be protein (as is the case in the majority of genes) or may be RNA (as is the case of genes that code for tRNA and rRNA). The crucial feature is that the product diffuses away from its site of synthesis to act elsewhere." [17]

The important parts of such definitions are: (1) that a gene corresponds to a transcription unit; (2) that genes produce both mRNA and noncoding RNAs; and (3) regulatory sequences control gene expression but are not part of the gene itself. However, there's one other important part of the definition and it is emphasized in Kostas Kampourakis' book "Making Sense of Genes."

"Therefore in this book I will consider genes as DNA sequences encoding information for functional products, be it proteins or RNA molecles. With 'encoding information,' I mean that the DNA sequence is used as a template for the production of an RNA molecule or a protein that performs some function.' [18]

The emphasis on function is essential because there are stretches of DNA that produce non-functional transcripts and they don't qualify as genes. These include obvious examples such as transcribed pseudogenes as well as less obvious examples such as junk RNA produced as noise due to transcription errors. In order to qualify as a true gene, by this definition, one has to prove that the transcript has a biological function. [18]

Early speculations on the size of a typical gene were based on high resolution genetic mapping and on the size of proteins and RNA molecules. A length of 1500 base pairs seemed reasonable at the time (1965). [13] This was based on the idea that the gene was the DNA that was directly responsible for production of the functional product. The discovery of introns in the 1970s meant that many eukaryotic genes were much larger than the size of the functional product would imply. Typical mammalian protein-coding genes, for example, are about 62,000 base pairs in length (transcribed region) and since there are about 20,000 of them they occupy about 35-40% of the mammalian genome (including the human genome). [19] [20] [21]

In spite of the fact that both protein-coding genes and noncoding genes have been known for more than 50 years, there are still a number of textbooks, websites, and scientific publications that define a gene as a DNA sequence that specifies a protein. In other words, the definition is restricted to protein-coding genes. Here's an example from a recent article in American Scientist.

What Is a Gene, Really?
... to truly assess the potential significance of de novo genes, we relied on a strict definition of the word "gene" with which nearly every expert can agree. First, in order for a nucleotide sequence to be considered a true gene, an open reading frame (ORF) must be present. The ORF can be thought of as the "gene itself"; it begins with a starting mark common for every gene and ends with one of three possible finish line signals. One of the key enzymes in this process, the RNA polymerase, zips along the strand of DNA like a train on a monorail, transcribing it into its messenger RNA form. This point brings us to our second important criterion: A true gene is one that is both transcribed and translated. That is, a true gene is first used as a template to make transient messenger RNA, which is then translated into a protein. [22]

This restricted definition is so common that it has spawned many recent articles that criticize this "standard definition" and call for a new expanded definition that includes noncoding genes. [23] [24] [25] However, this so-called "new" definition has been around for more than half a century and it's not clear why some modern writers are ignoring noncoding genes.

There are exceptions to the standard definition of a gene; for example, some viruses have an RNA genome. The one important exception concerns bacterial operons where a contiguous stretch of DNA containing multiple protein-coding regions is transcribed into one large mRNA. Scientists usually refer to each of the coding regions as separate genes in this case. The only significant controversy over the definition of a gene is whether to include the regulatory sequences that control transcription of the gene. The general consensus among scientists is that regulatory elements control the expression of a gene but are not part of the gene.


Gregor Mendel Gregor Mendel.png
Gregor Mendel

Discovery of discrete inherited units

The existence of discrete inheritable units was first suggested by Gregor Mendel (1822–1884). [26] From 1857 to 1864, in Brno, Austrian Empire (today's Czech Republic), he studied inheritance patterns in 8000 common edible pea plants, tracking distinct traits from parent to offspring. He described these mathematically as 2n combinations where n is the number of differing characteristics in the original peas. Although he did not use the term gene, he explained his results in terms of discrete inherited units that give rise to observable physical characteristics. This description prefigured Wilhelm Johannsen's distinction between genotype (the genetic material of an organism) and phenotype (the observable traits of that organism). Mendel was also the first to demonstrate independent assortment, the distinction between dominant and recessive traits, the distinction between a heterozygote and homozygote, and the phenomenon of discontinuous inheritance.

Prior to Mendel's work, the dominant theory of heredity was one of blending inheritance, [27] which suggested that each parent contributed fluids to the fertilization process and that the traits of the parents blended and mixed to produce the offspring. Charles Darwin developed a theory of inheritance he termed pangenesis, from Greek pan ("all, whole") and genesis ("birth") / genos ("origin"). [28] [29] Darwin used the term gemmule to describe hypothetical particles that would mix during reproduction.

Mendel's work went largely unnoticed after its first publication in 1866, but was rediscovered in the late 19th century by Hugo de Vries, Carl Correns, and Erich von Tschermak, who (claimed to have) reached similar conclusions in their own research. [30] Specifically, in 1889, Hugo de Vries published his book Intracellular Pangenesis, [31] in which he postulated that different characters have individual hereditary carriers and that inheritance of specific traits in organisms comes in particles. De Vries called these units "pangenes" (Pangens in German), after Darwin's 1868 pangenesis theory.

Twenty years later, in 1909, Wilhelm Johannsen introduced the term 'gene' [11] and in 1906, William Bateson, that of 'genetics' [32] [33] while Eduard Strasburger, amongst others, still used the term 'pangene' for the fundamental physical and functional unit of heredity. [31] :Translator's preface,viii

Discovery of DNA

Advances in understanding genes and inheritance continued throughout the 20th century. Deoxyribonucleic acid (DNA) was shown to be the molecular repository of genetic information by experiments in the 1940s to 1950s. [34] [35] The structure of DNA was studied by Rosalind Franklin and Maurice Wilkins using X-ray crystallography, which led James D. Watson and Francis Crick to publish a model of the double-stranded DNA molecule whose paired nucleotide bases indicated a compelling hypothesis for the mechanism of genetic replication. [36] [37]

In the early 1950s the prevailing view was that the genes in a chromosome acted like discrete entities, indivisible by recombination and arranged like beads on a string. The experiments of Benzer using mutants defective in the rII region of bacteriophage T4 (1955–1959) showed that individual genes have a simple linear structure and are likely to be equivalent to a linear section of DNA. [38] [39]

Collectively, this body of research established the central dogma of molecular biology, which states that proteins are translated from RNA, which is transcribed from DNA. This dogma has since been shown to have exceptions, such as reverse transcription in retroviruses. The modern study of genetics at the level of DNA is known as molecular genetics.

In 1972, Walter Fiers and his team were the first to determine the sequence of a gene: that of Bacteriophage MS2 coat protein. [40] The subsequent development of chain-termination DNA sequencing in 1977 by Frederick Sanger improved the efficiency of sequencing and turned it into a routine laboratory tool. [41] An automated version of the Sanger method was used in early phases of the Human Genome Project. [42]

Modern synthesis and its successors

The theories developed in the early 20th century to integrate Mendelian genetics with Darwinian evolution are called the modern synthesis, a term introduced by Julian Huxley. [43]

Evolutionary biologists have subsequently modified this concept, such as George C. Williams' gene-centric view of evolution. He proposed an evolutionary concept of the gene as a unit of natural selection with the definition: "that which segregates and recombines with appreciable frequency." [44] :24 In this view, the molecular gene transcribes as a unit, and the evolutionary gene inherits as a unit. Related ideas emphasizing the centrality of genes in evolution were popularized by Richard Dawkins. [12] [45]

Molecular basis

The chemical structure of a four base pair fragment of a DNA double helix. The sugar-phosphate backbone chains run in opposite directions with the bases pointing inwards, base-pairing A to T and C to G with hydrogen bonds. DNA chemical structure 2.svg
The chemical structure of a four base pair fragment of a DNA double helix. The sugar-phosphate backbone chains run in opposite directions with the bases pointing inwards, base-pairing A to T and C to G with hydrogen bonds.


The vast majority of organisms encode their genes in long strands of DNA (deoxyribonucleic acid). DNA consists of a chain made from four types of nucleotide subunits, each composed of: a five-carbon sugar (2-deoxyribose), a phosphate group, and one of the four bases adenine, cytosine, guanine, and thymine. [46] :2.1

Two chains of DNA twist around each other to form a DNA double helix with the phosphate-sugar backbone spiraling around the outside, and the bases pointing inwards with adenine base pairing to thymine and guanine to cytosine. The specificity of base pairing occurs because adenine and thymine align to form two hydrogen bonds, whereas cytosine and guanine form three hydrogen bonds. The two strands in a double helix must, therefore, be complementary, with their sequence of bases matching such that the adenines of one strand are paired with the thymines of the other strand, and so on. [46] :4.1

Due to the chemical composition of the pentose residues of the bases, DNA strands have directionality. One end of a DNA polymer contains an exposed hydroxyl group on the deoxyribose; this is known as the 3' end of the molecule. The other end contains an exposed phosphate group; this is the 5' end. The two strands of a double-helix run in opposite directions. Nucleic acid synthesis, including DNA replication and transcription occurs in the 5'→3' direction, because new nucleotides are added via a dehydration reaction that uses the exposed 3' hydroxyl as a nucleophile. [47] :27.2

The expression of genes encoded in DNA begins by transcribing the gene into RNA, a second type of nucleic acid that is very similar to DNA, but whose monomers contain the sugar ribose rather than deoxyribose. RNA also contains the base uracil in place of thymine. RNA molecules are less stable than DNA and are typically single-stranded. Genes that encode proteins are composed of a series of three-nucleotide sequences called codons, which serve as the "words" in the genetic "language". The genetic code specifies the correspondence during protein translation between codons and amino acids. The genetic code is nearly the same for all known organisms. [46] :4.1


Fluorescent microscopy image of a human female karyotype, showing 23 pairs of chromosomes. The DNA is stained red, with regions rich in housekeeping genes further stained in green. The largest chromosomes are around 10 times the size of the smallest. PLoSBiol3.5.Fig7ChromosomesAluFish.jpg
Fluorescent microscopy image of a human female karyotype, showing 23 pairs of chromosomes. The DNA is stained red, with regions rich in housekeeping genes further stained in green. The largest chromosomes are around 10 times the size of the smallest.

The total complement of genes in an organism or cell is known as its genome, which may be stored on one or more chromosomes. A chromosome consists of a single, very long DNA helix on which thousands of genes are encoded. [46] :4.2 The region of the chromosome at which a particular gene is located is called its locus. Each locus contains one allele of a gene; however, members of a population may have different alleles at the locus, each with a slightly different gene sequence.

The majority of eukaryotic genes are stored on a set of large, linear chromosomes. The chromosomes are packed within the nucleus in complex with storage proteins called histones to form a unit called a nucleosome. DNA packaged and condensed in this way is called chromatin. [46] :4.2 The manner in which DNA is stored on the histones, as well as chemical modifications of the histone itself, regulate whether a particular region of DNA is accessible for gene expression. In addition to genes, eukaryotic chromosomes contain sequences involved in ensuring that the DNA is copied without degradation of end regions and sorted into daughter cells during cell division: replication origins, telomeres and the centromere. [46] :4.2 Replication origins are the sequence regions where DNA replication is initiated to make two copies of the chromosome. Telomeres are long stretches of repetitive sequences that cap the ends of the linear chromosomes and prevent degradation of coding and regulatory regions during DNA replication. The length of the telomeres decreases each time the genome is replicated and has been implicated in the aging process. [49] The centromere is required for binding spindle fibres to separate sister chromatids into daughter cells during cell division. [46] :18.2

Prokaryotes (bacteria and archaea) typically store their genomes on a single large, circular chromosome. Similarly, some eukaryotic organelles contain a remnant circular chromosome with a small number of genes. [46] :14.4 Prokaryotes sometimes supplement their chromosome with additional small circles of DNA called plasmids, which usually encode only a few genes and are transferable between individuals. For example, the genes for antibiotic resistance are usually encoded on bacterial plasmids and can be passed between individual cells, even those of different species, via horizontal gene transfer. [50]

Whereas the chromosomes of prokaryotes are relatively gene-dense, those of eukaryotes often contain regions of DNA that serve no obvious function. Simple single-celled eukaryotes have relatively small amounts of such DNA, whereas the genomes of complex multicellular organisms, including humans, contain an absolute majority of DNA without an identified function. [51] This DNA has often been referred to as "junk DNA". However, more recent analyses suggest that, although protein-coding DNA makes up barely 2% of the human genome, about 80% of the bases in the genome may be expressed, so the term "junk DNA" may be a misnomer. [10]

Structure and function


Interactive icon.svg
The structure of a eukaryotic protein-coding gene. Regulatory sequence controls when and where expression occurs for the protein coding region (red). Promoter and enhancer regions (yellow) regulate the transcription of the gene into a pre-mRNA which is modified to remove introns (light grey) and add a 5' cap and poly-A tail (dark grey). The mRNA 5' and 3' untranslated regions (blue) regulate translation into the final protein product. [52]

The structure of a protein-coding gene consists of many elements of which the actual protein coding sequence is often only a small part. These include introns and untranslated regions of the mature mRNA. Noncoding genes can also contain introns that are removed during processing to produce the mature functional RNA.

All genes are associated with regulatory sequences that are required for their expression. First, genes require a promoter sequence. The promoter is recognized and bound by transcription factors that recruit and help RNA polymerase bind to the region to initiate transcription. [46] :7.1 The recognition typically occurs as a consensus sequence like the TATA box. A gene can have more than one promoter, resulting in messenger RNAs (mRNA) that differ in how far they extend in the 5' end. [53] Highly transcribed genes have "strong" promoter sequences that form strong associations with transcription factors, thereby initiating transcription at a high rate. Others genes have "weak" promoters that form weak associations with transcription factors and initiate transcription less frequently. [46] :7.2 Eukaryotic promoter regions are much more complex and difficult to identify than prokaryotic promoters. [46] :7.3

Additionally, genes can have regulatory regions many kilobases upstream or downstream of the gene that alter expression. These act by binding to transcription factors which then cause the DNA to loop so that the regulatory sequence (and bound transcription factor) become close to the RNA polymerase binding site. [54] For example, enhancers increase transcription by binding an activator protein which then helps to recruit the RNA polymerase to the promoter; conversely silencers bind repressor proteins and make the DNA less available for RNA polymerase. [55]

The mature messenger RNA produced from protein-coding genes contains untranslated regions at both ends which contain binding sites for ribosomes, RNA-binding proteins, miRNA, as well as terminator, and start and stop codons. [56] In addition, most eukaryotic open reading frames contain untranslated introns, which are removed and exons, which are connected together in a process known as RNA splicing. Finally, the ends of gene transcripts are defined by cleavage and polyadenylation (CPA) sites, where newly produced pre-mRNA gets cleaved and a string of ~200 adenosine monophosphates is added at the 3' end. The poly(A) tail protects mature mRNA from degradation and has other functions, affecting translation, localization, and transport of the transcript from the nucleus. Splicing, followed by CPA, generate the final mature mRNA, which encodes the protein or RNA product. [57] Although the general mechanisms defining locations of human genes are known, identification of the exact factors regulating these cellular processes is an area of active research. For example, known sequence features in the 3'-UTR can only explain half of all human gene ends. [58]

Many noncoding genes in eukaryotes have different transcription termination mechanisms and they do not have pol(A) tails.

Many prokaryotic genes are organized into operons, with multiple protein-coding sequences that are transcribed as a unit. [59] [60] The genes in an operon are transcribed as a continuous messenger RNA, referred to as a polycistronic mRNA. The term cistron in this context is equivalent to gene. The transcription of an operon's mRNA is often controlled by a repressor that can occur in an active or inactive state depending on the presence of specific metabolites. [61] When active, the repressor binds to a DNA sequence at the beginning of the operon, called the operator region, and represses transcription of the operon; when the repressor is inactive transcription of the operon can occur (see e.g. Lac operon). The products of operon genes typically have related functions and are involved in the same regulatory network. [46] :7.3

Functional definitions

Defining exactly what section of a DNA sequence comprises a gene is difficult. [8] [62] Regulatory regions of a gene such as enhancers do not necessarily have to be close to the coding sequence on the linear molecule because the intervening DNA can be looped out to bring the gene and its regulatory region into proximity. Similarly, a gene's introns can be much larger than its exons. Regulatory regions can even be on entirely different chromosomes and operate in trans to allow regulatory regions on one chromosome to come in contact with target genes on another chromosome. [63] [64]

Early work in molecular genetics suggested the concept that one gene makes one protein. This concept (originally called the one gene-one enzyme hypothesis) emerged from an influential 1941 paper by George Beadle and Edward Tatum on experiments with mutants of the fungus Neurospora crassa . [65] Norman Horowitz, an early colleague on the Neurospora research, reminisced in 2004 that "these experiments founded the science of what Beadle and Tatum called biochemical genetics. In actuality they proved to be the opening gun in what became molecular genetics and all the developments that have followed from that". [66] The one gene-one protein concept has been refined since the discovery of genes that can encode multiple proteins by alternative splicing and coding sequences split in short section across the genome whose mRNAs are concatenated by trans-splicing. [10] [67] [68]

A broad operational definition is sometimes used to encompass the complexity of these diverse phenomena, where a gene is defined as a union of genomic sequences encoding a coherent set of potentially overlapping functional products. [33] This definition categorizes genes by their functional products (proteins or RNA) rather than their specific DNA loci, with regulatory elements classified as gene-associated regions. [33]

Overlap between genes

It is also possible for genes to overlap the same DNA sequence and be considered distinct but overlapping genes. [69] The current definition of an overlapping gene is different across eukaryotes, prokaryotes, and viruses. In Eukaryotes they have recently been defined as "when at least one nucleotide is shared between the outermost boundaries of the primary transcripts of two or more genes, such that a DNA base mutation at the point of overlap would affect transcripts of all genes involved in the overlap." In Prokaryotes and Viruses they have recently been defined as "when the coding sequences of two genes share a nucleotide either on the same or opposite strands." [69]

Gene expression

In all organisms, two steps are required to read the information encoded in a gene's DNA and produce the protein it specifies. First, the gene's DNA is transcribed to messenger RNA (mRNA). [46] :6.1 Second, that mRNA is translated to protein. [46] :6.2 RNA-coding genes must still go through the first step, but are not translated into protein. [70] The process of producing a biologically functional molecule of either RNA or protein is called gene expression, and the resulting molecule is called a gene product.

Genetic code

Schematic of a single-stranded RNA molecule illustrating a series of three-base codons. Each three-nucleotide codon corresponds to an amino acid when translated to protein RNA-codons-aminoacids.svg
Schematic of a single-stranded RNA molecule illustrating a series of three-base codons. Each three-nucleotide codon corresponds to an amino acid when translated to protein

The nucleotide sequence of a gene's DNA specifies the amino acid sequence of a protein through the genetic code. Sets of three nucleotides, known as codons, each correspond to a specific amino acid. [46] :6 The principle that three sequential bases of DNA code for each amino acid was demonstrated in 1961 using frameshift mutations in the rIIB gene of bacteriophage T4 [71] (see Crick, Brenner et al. experiment).

Additionally, a "start codon", and three "stop codons" indicate the beginning and end of the protein coding region. There are 64 possible codons (four possible nucleotides at each of three positions, hence 43 possible codons) and only 20 standard amino acids; hence the code is redundant and multiple codons can specify the same amino acid. The correspondence between codons and amino acids is nearly universal among all known living organisms. [72]


Transcription produces a single-stranded RNA molecule known as messenger RNA, whose nucleotide sequence is complementary to the DNA from which it was transcribed. [46] :6.1 The mRNA acts as an intermediate between the DNA gene and its final protein product. The gene's DNA is used as a template to generate a complementary mRNA. The mRNA matches the sequence of the gene's DNA coding strand because it is synthesised as the complement of the template strand. Transcription is performed by an enzyme called an RNA polymerase, which reads the template strand in the 3' to 5'  direction and synthesizes the RNA from 5' to 3'. To initiate transcription, the polymerase first recognizes and binds a promoter region of the gene. Thus, a major mechanism of gene regulation is the blocking or sequestering the promoter region, either by tight binding by repressor molecules that physically block the polymerase or by organizing the DNA so that the promoter region is not accessible. [46] :7

In prokaryotes, transcription occurs in the cytoplasm; for very long transcripts, translation may begin at the 5'  end of the RNA while the 3' end is still being transcribed. In eukaryotes, transcription occurs in the nucleus, where the cell's DNA is stored. The RNA molecule produced by the polymerase is known as the primary transcript and undergoes post-transcriptional modifications before being exported to the cytoplasm for translation. One of the modifications performed is the splicing of introns which are sequences in the transcribed region that do not encode a protein. Alternative splicing mechanisms can result in mature transcripts from the same gene having different sequences and thus coding for different proteins. This is a major form of regulation in eukaryotic cells and also occurs in some prokaryotes. [46] :7.5 [73]


Protein coding genes are transcribed to an mRNA intermediate, then translated to a functional protein. RNA-coding genes are transcribed to a functional non-coding RNA. (PDB: 3BSE, 1OBB, 3TRA ) DNA to protein or ncRNA.svg
Protein coding genes are transcribed to an mRNA intermediate, then translated to a functional protein. RNA-coding genes are transcribed to a functional non-coding RNA. ( PDB: 3BSE, 1OBB, 3TRA )

Translation is the process by which a mature mRNA molecule is used as a template for synthesizing a new protein. [46] :6.2 Translation is carried out by ribosomes, large complexes of RNA and protein responsible for carrying out the chemical reactions to add new amino acids to a growing polypeptide chain by the formation of peptide bonds. The genetic code is read three nucleotides at a time, in units called codons, via interactions with specialized RNA molecules called transfer RNA (tRNA). Each tRNA has three unpaired bases known as the anticodon that are complementary to the codon it reads on the mRNA. The tRNA is also covalently attached to the amino acid specified by the complementary codon. When the tRNA binds to its complementary codon in an mRNA strand, the ribosome attaches its amino acid cargo to the new polypeptide chain, which is synthesized from amino terminus to carboxyl terminus. During and after synthesis, most new proteins must fold to their active three-dimensional structure before they can carry out their cellular functions. [46] :3


Genes are regulated so that they are expressed only when the product is needed, since expression draws on limited resources. [46] :7 A cell regulates its gene expression depending on its external environment (e.g. available nutrients, temperature and other stresses), its internal environment (e.g. cell division cycle, metabolism, infection status), and its specific role if in a multicellular organism. Gene expression can be regulated at any step: from transcriptional initiation, to RNA processing, to post-translational modification of the protein. The regulation of lactose metabolism genes in E. coli (lac operon) was the first such mechanism to be described in 1961. [74]

RNA genes

A typical protein-coding gene is first copied into RNA as an intermediate in the manufacture of the final protein product. [46] :6.1 In other cases, the RNA molecules are the actual functional products, as in the synthesis of ribosomal RNA and transfer RNA. Some RNAs known as ribozymes are capable of enzymatic function, and microRNA has a regulatory role. The DNA sequences from which such RNAs are transcribed are known as non-coding RNA genes. [70]

Some viruses store their entire genomes in the form of RNA, and contain no DNA at all. [75] [76] Because they use RNA to store genes, their cellular hosts may synthesize their proteins as soon as they are infected and without the delay in waiting for transcription. [77] On the other hand, RNA retroviruses, such as HIV, require the reverse transcription of their genome from RNA into DNA before their proteins can be synthesized. RNA-mediated epigenetic inheritance has also been observed in plants and very rarely in animals. [78]


Inheritance of a gene that has two different alleles (blue and white). The gene is located on an autosomal chromosome. The white allele is recessive to the blue allele. The probability of each outcome in the children's generation is one quarter, or 25 percent. Autosomal recessive - mini.svg
Inheritance of a gene that has two different alleles (blue and white). The gene is located on an autosomal chromosome. The white allele is recessive to the blue allele. The probability of each outcome in the children's generation is one quarter, or 25 percent.

Organisms inherit their genes from their parents. Asexual organisms simply inherit a complete copy of their parent's genome. Sexual organisms have two copies of each chromosome because they inherit one complete set from each parent. [46] :1

Mendelian inheritance

According to Mendelian inheritance, variations in an organism's phenotype (observable physical and behavioral characteristics) are due in part to variations in its genotype (particular set of genes). Each gene specifies a particular trait with a different sequence of a gene (alleles) giving rise to different phenotypes. Most eukaryotic organisms (such as the pea plants Mendel worked on) have two alleles for each trait, one inherited from each parent. [46] :20

Alleles at a locus may be dominant or recessive; dominant alleles give rise to their corresponding phenotypes when paired with any other allele for the same trait, whereas recessive alleles give rise to their corresponding phenotype only when paired with another copy of the same allele. If you know the genotypes of the organisms, you can determine which alleles are dominant and which are recessive. For example, if the allele specifying tall stems in pea plants is dominant over the allele specifying short stems, then pea plants that inherit one tall allele from one parent and one short allele from the other parent will also have tall stems. Mendel's work demonstrated that alleles assort independently in the production of gametes, or germ cells, ensuring variation in the next generation. Although Mendelian inheritance remains a good model for many traits determined by single genes (including a number of well-known genetic disorders) it does not include the physical processes of DNA replication and cell division. [79] [80]

DNA replication and cell division

The growth, development, and reproduction of organisms relies on cell division; the process by which a single cell divides into two usually identical daughter cells. This requires first making a duplicate copy of every gene in the genome in a process called DNA replication. [46] :5.2 The copies are made by specialized enzymes known as DNA polymerases, which "reads" one strand of the double-helical DNA, known as the template strand, and synthesize a new complementary strand. Because the DNA double helix is held together by base pairing, the sequence of one strand completely specifies the sequence of its complement; hence only one strand needs to be read by the enzyme to produce a faithful copy. The process of DNA replication is semiconservative; that is, the copy of the genome inherited by each daughter cell contains one original and one newly synthesized strand of DNA. [46] :5.2

The rate of DNA replication in living cells was first measured as the rate of phage T4 DNA elongation in phage-infected E. coli and found to be impressively rapid. [81] During the period of exponential DNA increase at 37 °C, the rate of elongation was 749 nucleotides per second.

After DNA replication is complete, the cell must physically separate the two copies of the genome and divide into two distinct membrane-bound cells. [46] :18.2 In prokaryotes  (bacteria and archaea) this usually occurs via a relatively simple process called binary fission, in which each circular genome attaches to the cell membrane and is separated into the daughter cells as the membrane invaginates to split the cytoplasm into two membrane-bound portions. Binary fission is extremely fast compared to the rates of cell division in eukaryotes. Eukaryotic cell division is a more complex process known as the cell cycle; DNA replication occurs during a phase of this cycle known as S phase, whereas the process of segregating chromosomes and splitting the cytoplasm occurs during M phase. [46] :18.1

Molecular inheritance

The duplication and transmission of genetic material from one generation of cells to the next is the basis for molecular inheritance and the link between the classical and molecular pictures of genes. Organisms inherit the characteristics of their parents because the cells of the offspring contain copies of the genes in their parents' cells. In asexually reproducing organisms, the offspring will be a genetic copy or clone of the parent organism. In sexually reproducing organisms, a specialized form of cell division called meiosis produces cells called gametes or germ cells that are haploid, or contain only one copy of each gene. [46] :20.2 The gametes produced by females are called eggs or ova, and those produced by males are called sperm. Two gametes fuse to form a diploid fertilized egg, a single cell that has two sets of genes, with one copy of each gene from the mother and one from the father. [46] :20

During the process of meiotic cell division, an event called genetic recombination or crossing-over can sometimes occur, in which a length of DNA on one chromatid is swapped with a length of DNA on the corresponding homologous non-sister chromatid. This can result in reassortment of otherwise linked alleles. [46] :5.5 The Mendelian principle of independent assortment asserts that each of a parent's two genes for each trait will sort independently into gametes; which allele an organism inherits for one trait is unrelated to which allele it inherits for another trait. This is in fact only true for genes that do not reside on the same chromosome or are located very far from one another on the same chromosome. The closer two genes lie on the same chromosome, the more closely they will be associated in gametes and the more often they will appear together (known as genetic linkage). [82] Genes that are very close are essentially never separated because it is extremely unlikely that a crossover point will occur between them. [82]

Molecular evolution


DNA replication is for the most part extremely accurate, however errors (mutations) do occur. [46] :7.6 The error rate in eukaryotic cells can be as low as 10−8 per nucleotide per replication, [83] [84] whereas for some RNA viruses it can be as high as 10−3. [85] This means that each generation, each human genome accumulates 1–2 new mutations. [85] Small mutations can be caused by DNA replication and the aftermath of DNA damage and include point mutations in which a single base is altered and frameshift mutations in which a single base is inserted or deleted. Either of these mutations can change the gene by missense (change a codon to encode a different amino acid) or nonsense (a premature stop codon). [86] Larger mutations can be caused by errors in recombination to cause chromosomal abnormalities including the duplication, deletion, rearrangement or inversion of large sections of a chromosome. Additionally, DNA repair mechanisms can introduce mutational errors when repairing physical damage to the molecule. The repair, even with mutation, is more important to survival than restoring an exact copy, for example when repairing double-strand breaks. [46] :5.4

When multiple different alleles for a gene are present in a species's population it is called polymorphic. Most different alleles are functionally equivalent, however some alleles can give rise to different phenotypic traits. A gene's most common allele is called the wild type, and rare alleles are called mutants. The genetic variation in relative frequencies of different alleles in a population is due to both natural selection and genetic drift. [87] The wild-type allele is not necessarily the ancestor of less common alleles, nor is it necessarily fitter.

Most mutations within genes are neutral, having no effect on the organism's phenotype (silent mutations). Some mutations do not change the amino acid sequence because multiple codons encode the same amino acid (synonymous mutations). Other mutations can be neutral if they lead to amino acid sequence changes, but the protein still functions similarly with the new amino acid (e.g. conservative mutations). Many mutations, however, are deleterious or even lethal, and are removed from populations by natural selection. Genetic disorders are the result of deleterious mutations and can be due to spontaneous mutation in the affected individual, or can be inherited. Finally, a small fraction of mutations are beneficial, improving the organism's fitness and are extremely important for evolution, since their directional selection leads to adaptive evolution. [46] :7.6

Sequence homology

A sequence alignment, produced by ClustalO, of mammalian histone proteins Histone Alignment.png
A sequence alignment, produced by ClustalO, of mammalian histone proteins

Genes with a most recent common ancestor, and thus a shared evolutionary ancestry, are known as homologs. [88] These genes appear either from gene duplication within an organism's genome, where they are known as paralogous genes, or are the result of divergence of the genes after a speciation event, where they are known as orthologous genes, [46] :7.6 and often perform the same or similar functions in related organisms. It is often assumed that the functions of orthologous genes are more similar than those of paralogous genes, although the difference is minimal. [89] [90]

The relationship between genes can be measured by comparing the sequence alignment of their DNA. [46] :7.6 The degree of sequence similarity between homologous genes is called conserved sequence. Most changes to a gene's sequence do not affect its function and so genes accumulate mutations over time by neutral molecular evolution. Additionally, any selection on a gene will cause its sequence to diverge at a different rate. Genes under stabilizing selection are constrained and so change more slowly whereas genes under directional selection change sequence more rapidly. [91] The sequence differences between genes can be used for phylogenetic analyses to study how those genes have evolved and how the organisms they come from are related. [92] [93]

Origins of new genes

Evolutionary fate of duplicate genes. Evolution fate duplicate genes - vector.svg
Evolutionary fate of duplicate genes.

The most common source of new genes in eukaryotic lineages is gene duplication, which creates copy number variation of an existing gene in the genome. [94] [95] The resulting genes (paralogs) may then diverge in sequence and in function. Sets of genes formed in this way compose a gene family. Gene duplications and losses within a family are common and represent a major source of evolutionary biodiversity. [96] Sometimes, gene duplication may result in a nonfunctional copy of a gene, or a functional copy may be subject to mutations that result in loss of function; such nonfunctional genes are called pseudogenes. [46] :7.6

"Orphan" genes, whose sequence shows no similarity to existing genes, are less common than gene duplicates. The human genome contains an estimate 18 [97] to 60 [98] genes with no identifiable homologs outside humans. Orphan genes arise primarily from either de novo emergence from previously non-coding sequence, or gene duplication followed by such rapid sequence change that the original relationship becomes undetectable. [99] De novo genes are typically shorter and simpler in structure than most eukaryotic genes, with few if any introns. [94] Over long evolutionary time periods, de novo gene birth may be responsible for a significant fraction of taxonomically restricted gene families. [100]

Horizontal gene transfer refers to the transfer of genetic material through a mechanism other than reproduction. This mechanism is a common source of new genes in prokaryotes, sometimes thought to contribute more to genetic variation than gene duplication. [101] It is a common means of spreading antibiotic resistance, virulence, and adaptive metabolic functions. [50] [102] Although horizontal gene transfer is rare in eukaryotes, likely examples have been identified of protist and alga genomes containing genes of bacterial origin. [103] [104]


The genome is the total genetic material of an organism and includes both the genes and non-coding sequences. [105] Eukaryotic genes can be annotated using FINDER. [106]

Number of genes

Depiction of numbers of genes for representative plants (green), vertebrates (blue), invertebrates (orange), fungi (yellow), bacteria (purple), and viruses (grey). An inset on the right shows the smaller genomes expanded 100-fold area-wise. Gene numbers.svg
Depiction of numbers of genes for representative plants (green), vertebrates (blue), invertebrates (orange), fungi (yellow), bacteria (purple), and viruses (grey). An inset on the right shows the smaller genomes expanded 100-fold area-wise.

The genome size, and the number of genes it encodes varies widely between organisms. The smallest genomes occur in viruses, [115] and viroids (which act as a single non-coding RNA gene). [116] Conversely, plants can have extremely large genomes, [117] with rice containing >46,000 protein-coding genes. [111] The total number of protein-coding genes (the Earth's proteome) is estimated to be 5 million sequences. [118]

Although the number of base-pairs of DNA in the human genome has been known since the 1960s, the estimated number of genes has changed over time as definitions of genes, and methods of detecting them have been refined. Initial theoretical predictions of the number of human genes were as high as 2,000,000. [119] Early experimental measures indicated there to be 50,000–100,000 transcribed genes (expressed sequence tags). [120] Subsequently, the sequencing in the Human Genome Project indicated that many of these transcripts were alternative variants of the same genes, and the total number of protein-coding genes was revised down to ~20,000 [114] with 13 genes encoded on the mitochondrial genome. [112] With the GENCODE annotation project, that estimate has continued to fall to 19,000. [121] Of the human genome, only 1–2% consists of protein-coding sequences, [122] with the remainder being 'noncoding' DNA such as introns, retrotransposons, and noncoding RNAs. [122] [123] Every multicellular organism has all its genes in each cell of its body but not every gene functions in every cell .

Essential genes

Gene functions in the minimal genome of the synthetic organism, Syn 3. Syn3 genome.svg
Gene functions in the minimal genome of the synthetic organism, Syn 3 .

Essential genes are the set of genes thought to be critical for an organism's survival. [125] This definition assumes the abundant availability of all relevant nutrients and the absence of environmental stress. Only a small portion of an organism's genes are essential. In bacteria, an estimated 250–400 genes are essential for Escherichia coli and Bacillus subtilis , which is less than 10% of their genes. [126] [127] [128] Half of these genes are orthologs in both organisms and are largely involved in protein synthesis. [128] In the budding yeast Saccharomyces cerevisiae the number of essential genes is slightly higher, at 1000 genes (~20% of their genes). [129] Although the number is more difficult to measure in higher eukaryotes, mice and humans are estimated to have around 2000 essential genes (~10% of their genes). [130] The synthetic organism, Syn 3 , has a minimal genome of 473 essential genes and quasi-essential genes (necessary for fast growth), although 149 have unknown function. [124]

Essential genes include housekeeping genes (critical for basic cell functions) [131] as well as genes that are expressed at different times in the organisms development or life cycle. [132] Housekeeping genes are used as experimental controls when analysing gene expression, since they are constitutively expressed at a relatively constant level.

Genetic and genomic nomenclature

Gene nomenclature has been established by the HUGO Gene Nomenclature Committee (HGNC), a committee of the Human Genome Organisation, for each known human gene in the form of an approved gene name and symbol (short-form abbreviation), which can be accessed through a database maintained by HGNC. Symbols are chosen to be unique, and each gene has only one symbol (although approved symbols sometimes change). Symbols are preferably kept consistent with other members of a gene family and with homologs in other species, particularly the mouse due to its role as a common model organism. [133]

Genetic engineering

Comparison of conventional plant breeding with transgenic and cisgenic genetic modification. Breeding transgenesis cisgenesis.svg
Comparison of conventional plant breeding with transgenic and cisgenic genetic modification.

Genetic engineering is the modification of an organism's genome through biotechnology. Since the 1970s, a variety of techniques have been developed to specifically add, remove and edit genes in an organism. [134] Recently developed genome engineering techniques use engineered nuclease enzymes to create targeted DNA repair in a chromosome to either disrupt or edit a gene when the break is repaired. [135] [136] [137] [138] The related term synthetic biology is sometimes used to refer to extensive genetic engineering of an organism. [139]

Genetic engineering is now a routine research tool with model organisms. For example, genes are easily added to bacteria [140] and lineages of knockout mice with a specific gene's function disrupted are used to investigate that gene's function. [141] [142] Many organisms have been genetically modified for applications in agriculture, industrial biotechnology, and medicine.

For multicellular organisms, typically the embryo is engineered which grows into the adult genetically modified organism. [143] However, the genomes of cells in an adult organism can be edited using gene therapy techniques to treat genetic diseases.

See also

Related Research Articles

<span class="mw-page-title-main">Genetics</span> Science of genes, heredity, and variation in living organisms

Genetics is a branch of biology concerned with the study of genes, genetic variation, and heredity in organisms. Gregor Mendel, a Moravian Augustinian friar working in the 19th century in Brno, was the first to study genetics scientifically. Mendel studied "trait inheritance", patterns in the way traits are handed down from parents to offspring over time. He observed that organisms inherit traits by way of discrete "units of inheritance". This term, still used today, is a somewhat ambiguous definition of what is referred to as a gene.

<span class="mw-page-title-main">Genetic code</span> Rules by which information encoded within genetic material is translated into proteins

The genetic code is the set of rules used by living cells to translate information encoded within genetic material into proteins. Translation is accomplished by the ribosome, which links proteinogenic amino acids in an order specified by messenger RNA (mRNA), using transfer RNA (tRNA) molecules to carry amino acids and to read the mRNA three nucleotides at a time. The genetic code is highly similar among all organisms and can be expressed in a simple table with 64 entries.

<span class="mw-page-title-main">Mutation</span> Alteration in the nucleotide sequence of a genome

In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis, or meiosis or other types of damage to DNA, which then may undergo error-prone repair, cause an error during other forms of repair, or cause an error during replication. Mutations may also result from insertion or deletion of segments of DNA due to mobile genetic elements.

<span class="mw-page-title-main">Human genome</span> Complete set of nucleic acid sequences for humans

The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the nuclear genome and the mitochondrial genome. Human genomes include both protein-coding DNA sequences and various types of DNA that does not encode proteins. The latter is a diverse category that includes DNA coding for non-translated RNA, such as that for ribosomal RNA, transfer RNA, ribozymes, small nuclear RNAs, and several types of regulatory RNAs. It also includes promoters and their associated gene-regulatory elements, DNA playing structural and replicatory roles, such as scaffolding regions, telomeres, centromeres, and origins of replication, plus large numbers of transposable elements, inserted viral DNA, non-functional pseudogenes and simple, highly-repetitive sequences. Introns make up a large percentage of non-coding DNA. Some of this non-coding DNA is non-functional junk DNA, such as pseudogenes, but there is no firm consensus on the total amount of junk DNA.

Non-coding DNA (ncDNA) sequences are components of an organism's DNA that do not encode protein sequences. Some non-coding DNA is transcribed into functional non-coding RNA molecules. Other functional regions of the non-coding DNA fraction include regulatory sequences that control gene expression; scaffold attachment regions; origins of DNA replication; centromeres; and telomeres. Some non-coding regions appear to be mostly nonfunctional such as introns, pseudogenes, intergenic DNA, and fragments of transposons and viruses.

<span class="mw-page-title-main">Molecular evolution</span> Process of change in the sequence composition of cellular molecules across generations

Molecular evolution is the process of change in the sequence composition of cellular molecules such as DNA, RNA, and proteins across generations. The field of molecular evolution uses principles of evolutionary biology and population genetics to explain patterns in these changes. Major topics in molecular evolution concern the rates and impacts of single nucleotide changes, neutral evolution vs. natural selection, origins of new genes, the genetic nature of complex traits, the genetic basis of speciation, evolution of development, and ways that evolutionary forces influence genomic and phenotypic changes.

The coding region of a gene, also known as the coding sequence(CDS), is the portion of a gene's DNA or RNA that codes for protein. Studying the length, composition, regulation, splicing, structures, and functions of coding regions compared to non-coding regions over different species and time periods can provide a significant amount of important information regarding gene organization and evolution of prokaryotes and eukaryotes. This can further assist in mapping the human genome and developing gene therapy.

<span class="mw-page-title-main">Pseudogene</span> Functionless relative of a gene

Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Most arise as superfluous copies of functional genes, either directly by DNA duplication or indirectly by reverse transcription of an mRNA transcript. Pseudogenes are usually identified when genome sequence analysis finds gene-like sequences that lack regulatory sequences needed for transcription or translation, or whose coding sequences are obviously defective due to frameshifts or premature stop codons.

<span class="mw-page-title-main">Molecular genetics</span> Scientific study of genes at the molecular level

Molecular genetics is a sub-field of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the structure and/or function of genes in an organism's genome using genetic screens. The field of study is based on the merging of several sub-fields in biology: classical Mendelian inheritance, cellular biology, molecular biology, biochemistry, and biotechnology. Researchers search for mutations in a gene or induce mutations in a gene to link a gene sequence to a specific phenotype. Molecular genetics is a powerful methodology for linking mutations to genetic conditions that may aid the search for treatments/cures for various genetics diseases.

<span class="mw-page-title-main">Single-nucleotide polymorphism</span> Single nucleotide in genomic DNA at which different sequence alternatives exist

In genetics, a single-nucleotide polymorphism is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently large fraction of the population, many publications do not apply such a frequency threshold.

<span class="mw-page-title-main">Point mutation</span> Replacement, insertion, or deletion of a single DNA or RNA nucleotide

A point mutation is a genetic mutation where a single nucleotide base is changed, inserted or deleted from a DNA or RNA sequence of an organism's genome. Point mutations have a variety of effects on the downstream protein product—consequences that are moderately predictable based upon the specifics of the mutation. These consequences can range from no effect to deleterious effects, with regard to protein production, composition, and function.

<span class="mw-page-title-main">Silent mutation</span>

Silent mutations are mutations in DNA that do not have an observable effect on the organism's phenotype. They are a specific type of neutral mutation. The phrase silent mutation is often used interchangeably with the phrase synonymous mutation; however, synonymous mutations are not always silent, nor vice versa. Synonymous mutations can affect transcription, splicing, mRNA transport, and translation, any of which could alter phenotype, rendering the synonymous mutation non-silent. The substrate specificity of the tRNA to the rare codon can affect the timing of translation, and in turn the co-translational folding of the protein. This is reflected in the codon usage bias that is observed in many species. Mutations that cause the altered codon to produce an amino acid with similar functionality are often classified as silent; if the properties of the amino acid are conserved, this mutation does not usually significantly affect protein function.

<span class="mw-page-title-main">Human mitochondrial genetics</span> Study of the human mitochondrial genome

Human mitochondrial genetics is the study of the genetics of human mitochondrial DNA. The human mitochondrial genome is the entirety of hereditary information contained in human mitochondria. Mitochondria are small structures in cells that generate energy for the cell to use, and are hence referred to as the "powerhouses" of the cell.

Genetics, a discipline of biology, is the science of heredity and variation in living organisms.

This glossary of genetics is a list of definitions of terms and concepts commonly used in the study of genetics and related disciplines in biology, including molecular biology, cell biology, and evolutionary biology. It is intended as introductory material for novices; for more specific and technical detail, see the article corresponding to each term. For related terms, see Glossary of evolutionary biology.

<span class="mw-page-title-main">DNA and RNA codon tables</span> List of standard rules to translate DNA encoded information into proteins

A codon table can be used to translate a genetic code into a sequence of amino acids. The standard genetic code is traditionally represented as an RNA codon table, because when proteins are made in a cell by ribosomes, it is messenger RNA (mRNA) that directs protein synthesis. The mRNA sequence is determined by the sequence of genomic DNA. In this context, the standard genetic code is referred to as translation table 1. It can also be represented in a DNA codon table. The DNA codons in such tables occur on the sense DNA strand and are arranged in a 5′-to-3′ direction. Different tables with alternate codons are used depending on the source of the genetic code, such as from a cell nucleus, mitochondrion, plastid, or hydrogenosome.

Numerous key discoveries in biology have emerged from studies of RNA, including seminal work in the fields of biochemistry, genetics, microbiology, molecular biology, molecular evolution and structural biology. As of 2010, 30 scientists have been awarded Nobel Prizes for experimental work that includes studies of RNA. Specific discoveries of high biological significance are discussed in this article.

<span class="mw-page-title-main">Genome evolution</span> Process by which a genome changes in structure or size over time

Genome evolution is the process by which a genome changes in structure (sequence) or size over time. The study of genome evolution involves multiple fields such as structural analysis of the genome, the study of genomic parasites, gene and ancient genome duplications, polyploidy, and comparative genomics. Genome evolution is a constantly changing and evolving field due to the steadily growing number of sequenced genomes, both prokaryotic and eukaryotic, available to the scientific community and the public at large.

Periannan Senapathy is a molecular biologist, geneticist, author and entrepreneur. He is the founder, president and chief scientific officer at Genome International Corporation, a biotechnology, bioinformatics, and information technology firm based in Madison, Wisconsin, which develops computational genomics applications of next-generation DNA sequencing (NGS) and clinical decision support systems for analyzing patient genome data that aids in diagnosis and treatment of diseases.

The history of genetics can be represented on a timeline of events from the earliest work in the 1850s, to the DNA era starting in the 1940s, and the genomics era beginning in the 1970s.



  1. 1 2 "1909: The Word Gene Coined". Retrieved 8 March 2021. "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..."
  2. Roth SC (July 2019). "What is genomic medicine?". Journal of the Medical Library Association. University Library System, University of Pittsburgh. 107 (3): 442–448. doi:10.5195/jmla.2019.604. PMC   6579593 . PMID   31258451.
  3. 1 2 Orgogozo V, Peluffo AE, and Morizot B (2016). "Chapter One-The "Mendelian Gene" and the "Molecular Gene": Two Relevant Concepts of Genetic Units" (PDF). Current Topics in Developmental Biology. 119: 1–26. doi:10.1016/bs.ctdb.2016.03.002. PMID   27282022.
  4. "What is a gene?: MedlinePlus Genetics". MedlinePlus. 17 September 2020. Retrieved 4 January 2021.
  5. Hirsch ED (2002). The new dictionary of cultural literacy. Boston: Houghton Mifflin. ISBN   0-618-22647-8. OCLC   50166721.
  6. "Studying Genes". Retrieved 15 January 2021.
  7. Elston RC, Satagopan JM, Sun S (2012). "Genetic terminology". Statistical Human Genetics. Methods in Molecular Biology. Vol. 850. Humana Press. pp. 1–9. doi:10.1007/978-1-61779-555-8_1. ISBN   978-1-61779-554-1. PMC   4450815 . PMID   22307690.
  8. 1 2 Gericke N, Hagberg M (5 December 2006). "Definition of historical models of gene function and their relation to students' understanding of genetics". Science & Education. 16 (7–8): 849–881. Bibcode:2007Sc&Ed..16..849G. doi:10.1007/s11191-006-9064-4. S2CID   144613322.
  9. Pearson H (May 2006). "Genetics: what is a gene?". Nature. 441 (7092): 398–401. Bibcode:2006Natur.441..398P. doi:10.1038/441398a. PMID   16724031. S2CID   4420674.
  10. 1 2 3 Pennisi E (June 2007). "Genomics. DNA study forces rethink of what it means to be a gene". Science. 316 (5831): 1556–7. doi:10.1126/science.316.5831.1556. PMID   17569836. S2CID   36463252.
  11. 1 2 Johannsen W (1909). Elemente der exakten Erblichkeitslehre [Elements of the exact theory of heredity] (in German). Jena, Germany: Gustav Fischer. p. 124. From p. 124: "Dieses "etwas" in den Gameten bezw. in der Zygote, … – kurz, was wir eben Gene nennen wollen – bedingt sind." (This "something" in the gametes or in the zygote, which has crucial importance for the character of the organism, is usually called by the quite ambiguous term Anlagen [primordium, from the German word Anlage for "plan, arrangement ; rough sketch"]. Many other terms have been suggested, mostly unfortunately in closer connection with certain hypothetical opinions. The word "pangene", which was introduced by Darwin, is perhaps used most frequently in place of Anlagen. However, the word "pangene" was not well chosen, as it is a compound word containing the roots pan (the neuter form of Πας all, every) and gen (from γί-γ(ε)ν-ομαι, to become). Only the meaning of this latter [i.e., gen] comes into consideration here ; just the basic idea – [namely,] that a trait in the developing organism can be determined or is influenced by "something" in the gametes – should find expression. No hypothesis about the nature of this "something" should be postulated or supported by it. For that reason it seems simplest to use in isolation the last syllable gen from Darwin's well-known word, which alone is of interest to us, in order to replace, with it, the poor, ambiguous word Anlage. Thus we will say simply "gene" and "genes" for "pangene" and "pangenes". The word gene is completely free of any hypothesis ; it expresses only the established fact that in any case many traits of the organism are determined by specific, separable, and thus independent "conditions", "foundations", "plans" – in short, precisely what we want to call genes.)
  12. 1 2 Dawkins R (1976). The selfish gene. Oxford, UK: Oxford University Press.
  13. 1 2 Watson JD (1965). Molecular Biology of the Gene. New York, NY, USA: W.A. Benjamin, Inc.
  14. Judson HF (1996). The Eight Day of Creation (Expanded ed.). Plainview, NY (USA): Cold Spring Harbor Laboratory Press.
  15. Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD (1994). Molecular Biology of the Cell: Third Edition. London, UK: Garland Publishing, Inc. ISBN   0-8153-1619-4.
  16. Moran LA, Horton HR, Scrimgeour KG, Perry MD (2012). Principles of Biochemistry: Fifth Edition. Upper Saddle River, NJ, USA: Pearson.
  17. Lewin B (2004). Genes VIII. Upper Saddle River, NJ, USA: Pearson/Prentice Hall.
  18. 1 2 Kampourakis K (2017). Making Sense of Genes. Cambridge, UK: Cambridge University Press.
  19. Piovesan A, Pelleri MC, Antonaros F, Strippoli P, Caracausi M, and Vitale L (2019). "On the length, weight and GC content of the human genome". BMC Research Notes. 12 (1): 106–173. doi:10.1186/s13104-019-4137-z. PMC   6391780 . PMID   30813969.
  20. Hubé F, and Francastel C (2015). "Mammalian Introns: When the Junk Generates Molecular Diversity". International Journal of Molecular Sciences. 16 (3): 4429–4452. doi: 10.3390/ijms16034429 . PMC   4394429 . PMID   25710723.
  21. Francis WR, and Wörheide G (2017). "Similar ratios of introns to intergenic sequence across animal genomes". Genome Biology and Evolution. 9 (6): 1582–1598. doi:10.1093/gbe/evx103. PMC   5534336 . PMID   28633296.
  22. Mortola E, Long M (2021). "Turning Junk into Us: How Genes Are Born". American Scientist. 109: 174–182.
  23. Hopkin K (2009). "The Evolving Definition of a Gene: With the discovery that nearly all of the genome is transcribed, the definition of a "gene" needs another revision". BioScience. 59: 928–931. doi:10.1525/bio.2009.59.11.3. S2CID   88157272.
  24. Pearson H (2006). "What Is a Gene?". Nature. 441 (7092): 399–401. Bibcode:2006Natur.441..398P. doi:10.1038/441398a. PMID   16724031. S2CID   4420674.
  25. Pennisi E (2007). "DNA study forces rethink of what it means to be a gene". Science. 316 (5831): 1556–1557. doi:10.1126/science.316.5831.1556. PMID   17569836. S2CID   36463252.
  26. Noble D (September 2008). "Genes and causation". Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences. 366 (1878): 3001–15. Bibcode:2008RSPTA.366.3001N. doi: 10.1098/rsta.2008.0086 . PMID   18559318.
  27. "Blending Inheritance - an overview | ScienceDirect Topics".
  28. "genesis" . Oxford English Dictionary (Online ed.). Oxford University Press. (Subscription or participating institution membership required.)
  29. Magner LN (2002). A History of the Life Sciences (Third ed.). Marcel Dekker, CRC Press. p. 371. ISBN   978-0-203-91100-6.
  30. Henig RM (2000). The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, the Father of Genetics . Boston: Houghton Mifflin. pp.  1–9. ISBN   978-0395-97765-1.
  31. 1 2 de Vries H (1889). Intracellulare Pangenese [Intracellular Pangenesis] (in German). Translated by Gager CS. Jena: Verlag von Gustav Fischer. Translated in 1908 from German to English by Open Court Publishing Co., Chicago, 1910
  32. Bateson W. (1906) "The progress of genetic research" Report of the Third International Conference 1906 on Genetics, W. Wilks, ed. London, England: Royal Horticultural Society. pp. 90–97. From p. 91: " … the science itself [i.e. the study of the breeding and hybridisation of plants] is still nameless, and we can only describe our pursuit by cumbrous and often misleading periphrasis. To meet this difficulty I suggest for the consideration of this Congress the term Genetics, which sufficiently indicates that our labors are devoted to the elucidation of the phenomena of heredity and variation: in other words, to the physiology of Descent, with implied bearing on the theoretical problems of the evolutionist and the systematist, and application to the practical problems of breeders, whether of animals or plants."
  33. 1 2 3 Gerstein MB, Bruce C, Rozowsky JS, Zheng D, Du J, Korbel JO, et al. (June 2007). "What is a gene, post-ENCODE? History and updated definition". Genome Research. 17 (6): 669–81. doi: 10.1101/gr.6339607 . PMID   17567988.
  34. Avery OT, Macleod CM, McCarty M (February 1944). "Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types : Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated From Pneumococcus Type III". The Journal of Experimental Medicine. 79 (2): 137–58. doi:10.1084/jem.79.2.137. PMC   2135445 . PMID   19871359. Reprint: Avery OT, MacLeod CM, McCarty M (February 1979). "Studies on the chemical nature of the substance inducing transformation of pneumococcal types. Inductions of transformation by a desoxyribonucleic acid fraction isolated from pneumococcus type III". The Journal of Experimental Medicine. 149 (2): 297–326. doi:10.1084/jem.149.2.297. PMC   2184805 . PMID   33226.
  35. Hershey AD, Chase M (May 1952). "Independent functions of viral protein and nucleic acid in growth of bacteriophage". The Journal of General Physiology. 36 (1): 39–56. doi:10.1085/jgp.36.1.39. PMC   2147348 . PMID   12981234.
  36. Judson H (1979). The Eighth Day of Creation: Makers of the Revolution in Biology. Cold Spring Harbor Laboratory Press. pp. 51–169. ISBN   978-0-87969-477-7.
  37. Watson JD, Crick FH (April 1953). "Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid" (PDF). Nature. 171 (4356): 737–8. Bibcode:1953Natur.171..737W. doi:10.1038/171737a0. PMID   13054692. S2CID   4253007.
  38. Benzer S (June 1955). "Fine Structure of a Genetic Region in Bacteriophage". Proceedings of the National Academy of Sciences of the United States of America. 41 (6): 344–54. Bibcode:1955PNAS...41..344B. doi: 10.1073/pnas.41.6.344 . PMC   528093 . PMID   16589677.
  39. Benzer S (November 1959). "On the Topology of the Genetic Fine Structure". Proceedings of the National Academy of Sciences of the United States of America. 45 (11): 1607–20. Bibcode:1959PNAS...45.1607B. doi: 10.1073/pnas.45.11.1607 . PMC   222769 . PMID   16590553.
  40. Min Jou W, Haegeman G, Ysebaert M, Fiers W (May 1972). "Nucleotide sequence of the gene coding for the bacteriophage MS2 coat protein". Nature. 237 (5350): 82–8. Bibcode:1972Natur.237...82J. doi:10.1038/237082a0. PMID   4555447. S2CID   4153893.
  41. Sanger F, Nicklen S, Coulson AR (December 1977). "DNA sequencing with chain-terminating inhibitors". Proceedings of the National Academy of Sciences of the United States of America. 74 (12): 5463–7. Bibcode:1977PNAS...74.5463S. doi: 10.1073/pnas.74.12.5463 . PMC   431765 . PMID   271968.
  42. Adams JU (2008). "DNA Sequencing Technologies". Nature Education Knowledge. SciTable. Nature Publishing Group. 1 (1): 193.
  43. Huxley J (1942). Evolution: the Modern Synthesis. Cambridge, Massachusetts: MIT Press. ISBN   978-0262513661.
  44. Williams GC (2001). Adaptation and Natural Selection a Critique of Some Current Evolutionary Thought (Online ed.). Princeton: Princeton University Press. ISBN   9781400820108.
  45. Dawkins R (1989). The extended phenotype (Paperback ed.). Oxford: Oxford University Press. ISBN   978-0-19-286088-0.
  46. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002). Molecular Biology of the Cell (Fourth ed.). New York: Garland Science. ISBN   978-0-8153-3218-3.
  47. Stryer L, Berg JM, Tymoczko JL (2002). Biochemistry (5th ed.). San Francisco: W.H. Freeman. ISBN   978-0-7167-4955-4.
  48. Bolzer A, Kreth G, Solovei I, Koehler D, Saracoglu K, Fauth C, et al. (May 2005). "Three-dimensional maps of all chromosomes in human male fibroblast nuclei and prometaphase rosettes". PLOS Biology. 3 (5): e157. doi:10.1371/journal.pbio.0030157. PMC   1084335 . PMID   15839726. Open Access logo PLoS transparent.svg
  49. Braig M, Schmitt CA (March 2006). "Oncogene-induced senescence: putting the brakes on tumor development". Cancer Research. 66 (6): 2881–4. doi: 10.1158/0008-5472.CAN-05-4006 . PMID   16540631.
  50. 1 2 Bennett PM (March 2008). "Plasmid encoded antibiotic resistance: acquisition and transfer of antibiotic resistance genes in bacteria". British Journal of Pharmacology. 153 (Suppl 1): S347-57. doi:10.1038/sj.bjp.0707607. PMC   2268074 . PMID   18193080.
  51. International Human Genome Sequencing Consortium (October 2004). "Finishing the euchromatic sequence of the human genome". Nature. 431 (7011): 931–45. Bibcode:2004Natur.431..931H. doi: 10.1038/nature03001 . PMID   15496913.
  52. 1 2 Shafee, Thomas; Lowe, Rohan (2017). "Eukaryotic and prokaryotic gene structure". WikiJournal of Medicine. 4 (1). doi:10.15347/wjm/2017.002. ISSN   2002-4436.
  53. Mortazavi A, Williams BA, McCue K, Schaeffer L, Wold B (July 2008). "Mapping and quantifying mammalian transcriptomes by RNA-Seq". Nature Methods. 5 (7): 621–8. doi:10.1038/nmeth.1226. PMID   18516045. S2CID   205418589.
  54. Pennacchio LA, Bickmore W, Dean A, Nobrega MA, Bejerano G (April 2013). "Enhancers: five essential questions". Nature Reviews. Genetics. 14 (4): 288–95. doi:10.1038/nrg3458. PMC   4445073 . PMID   23503198.
  55. Maston GA, Evans SK, Green MR (2006). "Transcriptional regulatory elements in the human genome". Annual Review of Genomics and Human Genetics. 7: 29–59. doi:10.1146/annurev.genom.7.080505.115623. PMID   16719718.
  56. Mignone F, Gissi C, Liuni S, Pesole G (28 February 2002). "Untranslated regions of mRNAs". Genome Biology. 3 (3): REVIEWS0004. doi:10.1186/gb-2002-3-3-reviews0004. PMC   139023 . PMID   11897027.
  57. Bicknell AA, Cenik C, Chua HN, Roth FP, Moore MJ (December 2012). "Introns in UTRs: why we should stop ignoring them". BioEssays. 34 (12): 1025–34. doi:10.1002/bies.201200073. PMID   23108796. S2CID   5808466.
  58. Shkurin A, Hughes TR (June 2021). "Known sequence features can explain half of all human gene ends". NAR Genomics and Bioinformatics. 3 (2): lqab042. doi:10.1093/nargab/lqab042. PMC   8176999 . PMID   34104882.
  59. Salgado H, Moreno-Hagelsieb G, Smith TF, Collado-Vides J (June 2000). "Operons in Escherichia coli: genomic analyses and predictions". Proceedings of the National Academy of Sciences of the United States of America. 97 (12): 6652–7. Bibcode:2000PNAS...97.6652S. doi: 10.1073/pnas.110147297 . PMC   18690 . PMID   10823905.
  60. Blumenthal T (November 2004). "Operons in eukaryotes". Briefings in Functional Genomics & Proteomics. 3 (3): 199–211. doi: 10.1093/bfgp/3.3.199 . PMID   15642184.
  61. Jacob F, Monod J (June 1961). "Genetic regulatory mechanisms in the synthesis of proteins". Journal of Molecular Biology. 3 (3): 318–56. doi:10.1016/S0022-2836(61)80072-7. PMID   13718526.
  62. Kellis M, Wold B, Snyder MP, Bernstein BE, Kundaje A, Marinov GK, et al. (April 2014). "Defining functional DNA elements in the human genome". Proceedings of the National Academy of Sciences of the United States of America. 111 (17): 6131–8. Bibcode:2014PNAS..111.6131K. doi: 10.1073/pnas.1318948111 . PMC   4035993 . PMID   24753594.
  63. Spilianakis CG, Lalioti MD, Town T, Lee GR, Flavell RA (June 2005). "Interchromosomal associations between alternatively expressed loci". Nature. 435 (7042): 637–45. Bibcode:2005Natur.435..637S. doi:10.1038/nature03574. PMID   15880101. S2CID   1755326.
  64. Williams A, Spilianakis CG, Flavell RA (April 2010). "Interchromosomal association and gene regulation in trans". Trends in Genetics. 26 (4): 188–97. doi:10.1016/j.tig.2010.01.007. PMC   2865229 . PMID   20236724.
  65. Beadle GW, Tatum EL (November 1941). "Genetic Control of Biochemical Reactions in Neurospora". Proceedings of the National Academy of Sciences of the United States of America. 27 (11): 499–506. Bibcode:1941PNAS...27..499B. doi: 10.1073/pnas.27.11.499 . PMC   1078370 . PMID   16588492.
  66. Horowitz NH, Berg P, Singer M, Lederberg J, Susman M, Doebley J, Crow JF (January 2004). "A centennial: George W. Beadle, 1903-1989". Genetics. 166 (1): 1–10. doi:10.1534/genetics.166.1.1. PMC   1470705 . PMID   15020400.
  67. Marande W, Burger G (October 2007). "Mitochondrial DNA as a genomic jigsaw puzzle". Science. AAAS. 318 (5849): 415. Bibcode:2007Sci...318..415M. doi:10.1126/science.1148033. PMID   17947575. S2CID   30948765.
  68. Parra G, Reymond A, Dabbouseh N, Dermitzakis ET, Castelo R, Thomson TM, et al. (January 2006). "Tandem chimerism as a means to increase protein complexity in the human genome". Genome Research. 16 (1): 37–44. doi:10.1101/gr.4145906. PMC   1356127 . PMID   16344564.
  69. 1 2 Wright BW, Molloy MP, Jaschke PR (5 October 2021). "Overlapping genes in natural and engineered genomes". Nature Reviews Genetics. 23 (3): 154–168. doi:10.1038/s41576-021-00417-w. ISSN   1471-0064. PMC   8490965 . PMID   34611352.
  70. 1 2 Eddy SR (December 2001). "Non-coding RNA genes and the modern RNA world". Nature Reviews. Genetics. 2 (12): 919–29. doi:10.1038/35103511. PMID   11733745. S2CID   18347629.
  71. Crick FH, Barnett L, Brenner S, Watts-Tobin RJ (December 1961). "General nature of the genetic code for proteins". Nature. 192 (4809): 1227–32. Bibcode:1961Natur.192.1227C. doi:10.1038/1921227a0. PMID   13882203. S2CID   4276146.
  72. Crick FH (October 1962). "The genetic code". Scientific American. WH Freeman and Company. 207 (4): 66–74. Bibcode:1962SciAm.207d..66C. doi:10.1038/scientificamerican1062-66. PMID   13882204.
  73. Woodson SA (May 1998). "Ironing out the kinks: splicing and translation in bacteria". Genes & Development. 12 (9): 1243–7. doi: 10.1101/gad.12.9.1243 . PMID   9573040.
  74. Jacob F, Monod J (June 1961). "Genetic regulatory mechanisms in the synthesis of proteins". Journal of Molecular Biology. 3 (3): 318–56. doi:10.1016/S0022-2836(61)80072-7. PMID   13718526.
  75. Koonin EV, Dolja VV (January 1993). "Evolution and taxonomy of positive-strand RNA viruses: implications of comparative analysis of amino acid sequences". Critical Reviews in Biochemistry and Molecular Biology. 28 (5): 375–430. doi:10.3109/10409239309078440. PMID   8269709.
  76. Domingo E (2001). "RNA Virus Genomes". eLS. doi:10.1002/9780470015902.a0001488.pub2. ISBN   978-0470016176.
  77. Domingo E, Escarmís C, Sevilla N, Moya A, Elena SF, Quer J, et al. (June 1996). "Basic concepts in RNA virus evolution". FASEB Journal. 10 (8): 859–64. doi:10.1096/fasebj.10.8.8666162. PMID   8666162. S2CID   20865732.
  78. Morris KV, Mattick JS (June 2014). "The rise of regulatory RNA". Nature Reviews. Genetics. 15 (6): 423–37. doi:10.1038/nrg3722. PMC   4314111 . PMID   24776770.
  79. Miko I (2008). "Gregor Mendel and the Principles of Inheritance". Nature Education Knowledge. SciTable. Nature Publishing Group. 1 (1): 134.
  80. Chial H (2008). "Mendelian Genetics: Patterns of Inheritance and Single-Gene Disorders". Nature Education Knowledge. SciTable. Nature Publishing Group. 1 (1): 63.
  81. McCarthy D, Minner C, Bernstein H, Bernstein C (October 1976). "DNA elongation rates and growing point distributions of wild-type phage T4 and a DNA-delay amber mutant". Journal of Molecular Biology. 106 (4): 963–81. doi:10.1016/0022-2836(76)90346-6. PMID   789903.
  82. 1 2 Lobo I, Shaw K (2008). "Discovery and Types of Genetic Linkage". Nature Education Knowledge. SciTable. Nature Publishing Group. 1 (1): 139.
  83. Nachman MW, Crowell SL (September 2000). "Estimate of the mutation rate per nucleotide in humans". Genetics. 156 (1): 297–304. doi:10.1093/genetics/156.1.297. PMC   1461236 . PMID   10978293.
  84. Roach JC, Glusman G, Smit AF, Huff CD, Hubley R, Shannon PT, et al. (April 2010). "Analysis of genetic inheritance in a family quartet by whole-genome sequencing". Science. 328 (5978): 636–9. Bibcode:2010Sci...328..636R. doi:10.1126/science.1186802. PMC   3037280 . PMID   20220176.
  85. 1 2 Drake JW, Charlesworth B, Charlesworth D, Crow JF (April 1998). "Rates of spontaneous mutation". Genetics. 148 (4): 1667–86. doi:10.1093/genetics/148.4.1667. PMC   1460098 . PMID   9560386.
  86. "What kinds of gene mutations are possible?". Genetics Home Reference. United States National Library of Medicine. 11 May 2015. Retrieved 19 May 2015.
  87. Andrews CA (2010). "Natural Selection, Genetic Drift, and Gene Flow Do Not Act in Isolation in Natural Populations". Nature Education Knowledge. SciTable. Nature Publishing Group. 3 (10): 5.
  88. Patterson C (November 1988). "Homology in classical and molecular biology". Molecular Biology and Evolution. 5 (6): 603–25. doi: 10.1093/oxfordjournals.molbev.a040523 . PMID   3065587.
  89. Studer RA, Robinson-Rechavi M (May 2009). "How confident can we be that orthologs are similar, but paralogs differ?". Trends in Genetics. 25 (5): 210–6. doi:10.1016/j.tig.2009.03.004. PMID   19368988.
  90. Altenhoff AM, Studer RA, Robinson-Rechavi M, Dessimoz C (2012). "Resolving the ortholog conjecture: orthologs tend to be weakly, but significantly, more similar in function than paralogs". PLOS Computational Biology. 8 (5): e1002514. Bibcode:2012PLSCB...8E2514A. doi:10.1371/journal.pcbi.1002514. PMC   3355068 . PMID   22615551. Open Access logo PLoS transparent.svg
  91. Nosil P, Funk DJ, Ortiz-Barrientos D (February 2009). "Divergent selection and heterogeneous genomic divergence". Molecular Ecology. 18 (3): 375–402. doi: 10.1111/j.1365-294X.2008.03946.x . PMID   19143936.
  92. Emery L (5 December 2014). "Introduction to Phylogenetics". EMBL-EBI. Retrieved 19 May 2015.
  93. Mitchell MW, Gonder MK (2013). "Primate Speciation: A Case Study of African Apes". Nature Education Knowledge. SciTable. Nature Publishing Group. 4 (2): 1.
  94. 1 2 Guerzoni D, McLysaght A (November 2011). "De novo origins of human genes". PLOS Genetics. 7 (11): e1002381. doi:10.1371/journal.pgen.1002381. PMC   3213182 . PMID   22102832. Open Access logo PLoS transparent.svg
  95. Reams AB, Roth JR (February 2015). "Mechanisms of gene duplication and amplification". Cold Spring Harbor Perspectives in Biology. 7 (2): a016592. doi:10.1101/cshperspect.a016592. PMC   4315931 . PMID   25646380.
  96. Demuth JP, De Bie T, Stajich JE, Cristianini N, Hahn MW (December 2006). "The evolution of mammalian gene families". PLOS ONE. 1 (1): e85. Bibcode:2006PLoSO...1...85D. doi: 10.1371/journal.pone.0000085 . PMC   1762380 . PMID   17183716. Open Access logo PLoS transparent.svg
  97. Knowles DG, McLysaght A (October 2009). "Recent de novo origin of human protein-coding genes". Genome Research. 19 (10): 1752–9. doi:10.1101/gr.095026.109. PMC   2765279 . PMID   19726446.
  98. Wu DD, Irwin DM, Zhang YP (November 2011). "De novo origin of human protein-coding genes". PLOS Genetics. 7 (11): e1002379. doi:10.1371/journal.pgen.1002379. PMC   3213175 . PMID   22102831. Open Access logo PLoS transparent.svg
  99. McLysaght A, Guerzoni D (September 2015). "New genes from non-coding sequence: the role of de novo protein-coding genes in eukaryotic evolutionary innovation". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 370 (1678): 20140332. doi:10.1098/rstb.2014.0332. PMC   4571571 . PMID   26323763.
  100. Neme R, Tautz D (February 2013). "Phylogenetic patterns of emergence of new genes support a model of frequent de novo evolution". BMC Genomics. 14 (1): 117. doi:10.1186/1471-2164-14-117. PMC   3616865 . PMID   23433480.
  101. Treangen TJ, Rocha EP (January 2011). "Horizontal transfer, not duplication, drives the expansion of protein families in prokaryotes". PLOS Genetics. 7 (1): e1001284. doi:10.1371/journal.pgen.1001284. PMC   3029252 . PMID   21298028. Open Access logo PLoS transparent.svg
  102. Ochman H, Lawrence JG, Groisman EA (May 2000). "Lateral gene transfer and the nature of bacterial innovation". Nature. 405 (6784): 299–304. Bibcode:2000Natur.405..299O. doi:10.1038/35012500. PMID   10830951. S2CID   85739173.
  103. Keeling PJ, Palmer JD (August 2008). "Horizontal gene transfer in eukaryotic evolution". Nature Reviews. Genetics. 9 (8): 605–18. doi:10.1038/nrg2386. PMID   18591983. S2CID   213613.
  104. Schönknecht G, Chen WH, Ternes CM, Barbier GG, Shrestha RP, Stanke M, et al. (March 2013). "Gene transfer from bacteria and archaea facilitated evolution of an extremophilic eukaryote". Science. 339 (6124): 1207–10. Bibcode:2013Sci...339.1207S. doi:10.1126/science.1231707. PMID   23471408. S2CID   5502148.
  105. Ridley, M. (2006). Genome. New York, NY: Harper Perennial. ISBN   0-06-019497-9
  106. Banerjee S, Bhandary P, Woodhouse M, Sen TZ, Wise RP, Andorf CM (April 2021). "FINDER: an automated software package to annotate eukaryotic genes from RNA-Seq data and associated protein sequences". BMC Bioinformatics. 44 (9): e89. doi: 10.1186/s12859-021-04120-9 . PMC   8056616 . PMID   33879057.
  107. Watson, JD, Baker TA, Bell SP, Gann A, Levine M, Losick R. (2004). "Ch9-10", Molecular Biology of the Gene, 5th ed., Peason Benjamin Cummings; CSHL Press.
  108. "Integr8 – A.thaliana Genome Statistics".
  109. "Understanding the Basics". The Human Genome Project. Retrieved 26 April 2015.
  110. "WS227 Release Letter". WormBase. 10 August 2011. Archived from the original on 28 November 2013. Retrieved 19 November 2013.
  111. 1 2 Yu J, Hu S, Wang J, Wong GK, Li S, Liu B, et al. (April 2002). "A draft sequence of the rice genome (Oryza sativa L. ssp. indica)". Science. 296 (5565): 79–92. Bibcode:2002Sci...296...79Y. doi:10.1126/science.1068037. PMID   11935017. S2CID   208529258.
  112. 1 2 Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, et al. (April 1981). "Sequence and organization of the human mitochondrial genome". Nature. 290 (5806): 457–65. Bibcode:1981Natur.290..457A. doi:10.1038/290457a0. PMID   7219534. S2CID   4355527.
  113. Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, et al. (March 2000). "The genome sequence of Drosophila melanogaster". Science. 287 (5461): 2185–95. Bibcode:2000Sci...287.2185.. CiteSeerX . doi:10.1126/science.287.5461.2185. PMID   10731132.
  114. 1 2 Pertea M, Salzberg SL (2010). "Between a chicken and a grape: estimating the number of human genes". Genome Biology. 11 (5): 206. doi:10.1186/gb-2010-11-5-206. PMC   2898077 . PMID   20441615.
  115. Belyi VA, Levine AJ, Skalka AM (December 2010). "Sequences from ancestral single-stranded DNA viruses in vertebrate genomes: the parvoviridae and circoviridae are more than 40 to 50 million years old". Journal of Virology. 84 (23): 12458–62. doi:10.1128/JVI.01789-10. PMC   2976387 . PMID   20861255.
  116. Flores R, Di Serio F, Hernández C (February 1997). "Viroids: The Noncoding Genomes". Seminars in Virology. 8 (1): 65–73. doi:10.1006/smvy.1997.0107.
  117. Zonneveld BJ (2010). "New Record Holders for Maximum Genome Size in Eudicots and Monocots". Journal of Botany. 2010: 1–4. doi: 10.1155/2010/527357 .
  118. Perez-Iratxeta C, Palidwor G, Andrade-Navarro MA (December 2007). "Towards completion of the Earth's proteome". EMBO Reports. 8 (12): 1135–41. doi:10.1038/sj.embor.7401117. PMC   2267224 . PMID   18059312.
  119. Kauffman SA (March 1969). "Metabolic stability and epigenesis in randomly constructed genetic nets". Journal of Theoretical Biology. Elsevier. 22 (3): 437–67. Bibcode:1969JThBi..22..437K. doi:10.1016/0022-5193(69)90015-0. PMID   5803332.
  120. Schuler GD, Boguski MS, Stewart EA, Stein LD, Gyapay G, Rice K, et al. (October 1996). "A gene map of the human genome". Science. 274 (5287): 540–6. Bibcode:1996Sci...274..540S. doi:10.1126/science.274.5287.540. PMID   8849440. S2CID   22619.
  121. Chi KR (October 2016). "The dark side of the human genome". Nature. 538 (7624): 275–277. Bibcode:2016Natur.538..275C. doi: 10.1038/538275a . PMID   27734873.
  122. 1 2 Claverie JM (September 2005). "Fewer genes, more noncoding RNA". Science. 309 (5740): 1529–30. Bibcode:2005Sci...309.1529C. doi:10.1126/science.1116800. PMID   16141064. S2CID   28359091.
  123. Carninci P, Hayashizaki Y (April 2007). "Noncoding RNA transcription beyond annotated genes". Current Opinion in Genetics & Development. 17 (2): 139–44. doi:10.1016/j.gde.2007.02.008. PMID   17317145.
  124. 1 2 Hutchison CA, Chuang RY, Noskov VN, Assad-Garcia N, Deerinck TJ, Ellisman MH, et al. (March 2016). "Design and synthesis of a minimal bacterial genome". Science. 351 (6280): aad6253. Bibcode:2016Sci...351.....H. doi: 10.1126/science.aad6253 . PMID   27013737.
  125. Glass JI, Assad-Garcia N, Alperovich N, Yooseph S, Lewis MR, Maruf M, et al. (January 2006). "Essential genes of a minimal bacterium". Proceedings of the National Academy of Sciences of the United States of America. 103 (2): 425–30. Bibcode:2006PNAS..103..425G. doi: 10.1073/pnas.0510013103 . PMC   1324956 . PMID   16407165.
  126. Gerdes SY, Scholle MD, Campbell JW, Balázsi G, Ravasz E, Daugherty MD, et al. (October 2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655". Journal of Bacteriology. 185 (19): 5673–84. doi:10.1128/jb.185.19.5673-5684.2003. PMC   193955 . PMID   13129938.
  127. Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, et al. (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection". Molecular Systems Biology. 2: 2006.0008. doi:10.1038/msb4100050. PMC   1681482 . PMID   16738554.
  128. 1 2 Juhas M, Reuß DR, Zhu B, Commichau FM (November 2014). "Bacillus subtilis and Escherichia coli essential genes and minimal cell factories after one decade of genome engineering". Microbiology. 160 (Pt 11): 2341–2351. doi: 10.1099/mic.0.079376-0 . PMID   25092907.
  129. Tu Z, Wang L, Xu M, Zhou X, Chen T, Sun F (February 2006). "Further understanding human disease genes by comparing with housekeeping genes and other genes". BMC Genomics. 7: 31. doi:10.1186/1471-2164-7-31. PMC   1397819 . PMID   16504025. Open Access logo PLoS transparent.svg
  130. Georgi B, Voight BF, Bućan M (May 2013). "From mouse to human: evolutionary genomics analysis of human orthologs of essential genes". PLOS Genetics. 9 (5): e1003484. doi:10.1371/journal.pgen.1003484. PMC   3649967 . PMID   23675308. Open Access logo PLoS transparent.svg
  131. Eisenberg E, Levanon EY (October 2013). "Human housekeeping genes, revisited". Trends in Genetics. 29 (10): 569–74. doi:10.1016/j.tig.2013.05.010. PMID   23810203.
  132. Amsterdam A, Hopkins N (September 2006). "Mutagenesis strategies in zebrafish for identifying genes involved in development and disease". Trends in Genetics. 22 (9): 473–8. doi:10.1016/j.tig.2006.06.011. PMID   16844256.
  133. "About the HGNC". HGNC Database of Human Gene Names. HUGO Gene Nomenclature Committee. Retrieved 14 May 2015.
  134. Cohen SN, Chang AC (May 1973). "Recircularization and autonomous replication of a sheared R-factor DNA segment in Escherichia coli transformants". Proceedings of the National Academy of Sciences of the United States of America. 70 (5): 1293–7. Bibcode:1973PNAS...70.1293C. doi: 10.1073/pnas.70.5.1293 . PMC   433482 . PMID   4576014.
  135. Esvelt KM, Wang HH (2013). "Genome-scale engineering for systems and synthetic biology". Molecular Systems Biology. 9 (1): 641. doi:10.1038/msb.2012.66. PMC   3564264 . PMID   23340847.
  136. Tan WS, Carlson DF, Walton MW, Fahrenkrug SC, Hackett PB (2012). "Precision editing of large animal genomes". Advances in Genetics Volume 80. Advances in Genetics. Vol. 80. pp. 37–97. doi:10.1016/B978-0-12-404742-6.00002-8. ISBN   9780124047426. PMC   3683964 . PMID   23084873.
  137. Puchta H, Fauser F (2013). "Gene targeting in plants: 25 years later". The International Journal of Developmental Biology. 57 (6–8): 629–37. doi: 10.1387/ijdb.130194hp . PMID   24166445.
  138. Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F (November 2013). "Genome engineering using the CRISPR-Cas9 system". Nature Protocols. 8 (11): 2281–2308. doi:10.1038/nprot.2013.143. PMC   3969860 . PMID   24157548.
  139. Kittleson JT, Wu GC, Anderson JC (August 2012). "Successes and failures in modular genetic engineering". Current Opinion in Chemical Biology. 16 (3–4): 329–36. doi:10.1016/j.cbpa.2012.06.009. PMID   22818777.
  140. Berg P, Mertz JE (January 2010). "Personal reflections on the origins and emergence of recombinant DNA technology". Genetics. 184 (1): 9–17. doi:10.1534/genetics.109.112144. PMC   2815933 . PMID   20061565.
  141. Austin CP, Battey JF, Bradley A, Bucan M, Capecchi M, Collins FS, et al. (September 2004). "The knockout mouse project". Nature Genetics. 36 (9): 921–4. doi:10.1038/ng0904-921. PMC   2716027 . PMID   15340423.
  142. Guan C, Ye C, Yang X, Gao J (February 2010). "A review of current large-scale mouse knockout efforts". Genesis. 48 (2): 73–85. doi:10.1002/dvg.20594. PMID   20095055. S2CID   34470273.
  143. Deng C (October 2007). "In celebration of Dr. Mario R. Capecchi's Nobel Prize". International Journal of Biological Sciences. 3 (7): 417–9. doi:10.7150/ijbs.3.417. PMC   2043165 . PMID   17998949.


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