Gene duplication

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Gene duplication (or chromosomal duplication or gene amplification) is a major mechanism through which new genetic material is generated during molecular evolution. It can be defined as any duplication of a region of DNA that contains a gene. Gene duplications can arise as products of several types of errors in DNA replication and repair machinery as well as through fortuitous capture by selfish genetic elements. Common sources of gene duplications include ectopic recombination, retrotransposition event, aneuploidy, polyploidy, and replication slippage. [1]

Contents

Mechanisms of duplication

Ectopic recombination

Duplications arise from an event termed unequal crossing-over that occurs during meiosis between misaligned homologous chromosomes. The chance of it happening is a function of the degree of sharing of repetitive elements between two chromosomes. The products of this recombination are a duplication at the site of the exchange and a reciprocal deletion. Ectopic recombination is typically mediated by sequence similarity at the duplicate breakpoints, which form direct repeats. Repetitive genetic elements such as transposable elements offer one source of repetitive DNA that can facilitate recombination, and they are often found at duplication breakpoints in plants and mammals. [2]

Schematic of a region of a chromosome before and after a duplication event Gene-duplication.png
Schematic of a region of a chromosome before and after a duplication event

Replication slippage

Replication slippage is an error in DNA replication that can produce duplications of short genetic sequences. During replication DNA polymerase begins to copy the DNA. At some point during the replication process, the polymerase dissociates from the DNA and replication stalls. When the polymerase reattaches to the DNA strand, it aligns the replicating strand to an incorrect position and incidentally copies the same section more than once. Replication slippage is also often facilitated by repetitive sequences, but requires only a few bases of similarity.[ citation needed ]

Retrotransposition

Retrotransposons, mainly L1, can occasionally act on cellular mRNA. Transcripts are reverse transcribed to DNA and inserted into random place in the genome, creating retrogenes. Resulting sequence usually lack introns and often contain poly(A) sequences that are also integrated into the genome. Many retrogenes display changes in gene regulation in comparison to their parental gene sequences, which sometimes results in novel functions. Retrogenes can move between different chromosomes to shape chromosomal evolution. [3]

Aneuploidy

Aneuploidy occurs when nondisjunction at a single chromosome results in an abnormal number of chromosomes. Aneuploidy is often harmful and in mammals regularly leads to spontaneous abortions (miscarriages). Some aneuploid individuals are viable, for example trisomy 21 in humans, which leads to Down syndrome. Aneuploidy often alters gene dosage in ways that are detrimental to the organism; therefore, it is unlikely to spread through populations.

Polyploidy

Polyploidy, or whole genome duplication is a product of nondisjunction during meiosis which results in additional copies of the entire genome. Polyploidy is common in plants, but it has also occurred in animals, with two rounds of whole genome duplication (2R event) in the vertebrate lineage leading to humans. [4] It has also occurred in the hemiascomycete yeasts ~100 mya. [5] [6]

After a whole genome duplication, there is a relatively short period of genome instability, extensive gene loss, elevated levels of nucleotide substitution and regulatory network rewiring. [7] [8] In addition, gene dosage effects play a significant role. [9] Thus, most duplicates are lost within a short period, however, a considerable fraction of duplicates survive. [10] Interestingly, genes involved in regulation are preferentially retained. [11] [12] Furthermore, retention of regulatory genes, most notably the Hox genes, has led to adaptive innovation.

Rapid evolution and functional divergence have been observed at the level of the transcription of duplicated genes, usually by point mutations in short transcription factor binding motifs. [13] [14] Furthermore, rapid evolution of protein phosphorylation motifs, usually embedded within rapidly evolving intrinsically disordered regions is another contributing factor for survival and rapid adaptation/neofunctionalization of duplicate genes. [15] Thus, a link seems to exist between gene regulation (at least at the post-translational level) and genome evolution. [15]

Polyploidy is also a well known source of speciation, as offspring, which have different numbers of chromosomes compared to parent species, are often unable to interbreed with non-polyploid organisms. Whole genome duplications are thought to be less detrimental than aneuploidy as the relative dosage of individual genes should be the same.

As an evolutionary event

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

Rate of gene duplication

Comparisons of genomes demonstrate that gene duplications are common in most species investigated. This is indicated by variable copy numbers (copy number variation) in the genome of humans [16] [17] or fruit flies. [18] However, it has been difficult to measure the rate at which such duplications occur. Recent studies yielded a first direct estimate of the genome-wide rate of gene duplication in C. elegans , the first multicellular eukaryote for which such as estimate became available. The gene duplication rate in C. elegans is on the order of 10−7 duplications/gene/generation, that is, in a population of 10 million worms, one will have a gene duplication per generation. This rate is two orders of magnitude greater than the spontaneous rate of point mutation per nucleotide site in this species. [19] Older (indirect) studies reported locus-specific duplication rates in bacteria, Drosophila, and humans ranging from 10−3 to 10−7/gene/generation. [20] [21] [22]

Neofunctionalization

Gene duplications are an essential source of genetic novelty that can lead to evolutionary innovation. Duplication creates genetic redundancy, where the second copy of the gene is often free from selective pressure—that is, mutations of it have no deleterious effects to its host organism. If one copy of a gene experiences a mutation that affects its original function, the second copy can serve as a 'spare part' and continue to function correctly. Thus, duplicate genes accumulate mutations faster than a functional single-copy gene, over generations of organisms, and it is possible for one of the two copies to develop a new and different function. Some examples of such neofunctionalization is the apparent mutation of a duplicated digestive gene in a family of ice fish into an antifreeze gene and duplication leading to a novel snake venom gene [23] and the synthesis of 1 beta-hydroxytestosterone in pigs. [24]

Gene duplication is believed to play a major role in evolution; this stance has been held by members of the scientific community for over 100 years. [25] Susumu Ohno was one of the most famous developers of this theory in his classic book Evolution by gene duplication (1970). [26] Ohno argued that gene duplication is the most important evolutionary force since the emergence of the universal common ancestor. [27] Major genome duplication events can be quite common. It is believed that the entire yeast genome underwent duplication about 100 million years ago. [28] Plants are the most prolific genome duplicators. For example, wheat is hexaploid (a kind of polyploid), meaning that it has six copies of its genome.

Subfunctionalization

Another possible fate for duplicate genes is that both copies are equally free to accumulate degenerative mutations, so long as any defects are complemented by the other copy. This leads to a neutral "subfunctionalization" (a process of constructive neutral evolution) or DDC (duplication-degeneration-complementation) model, [29] [30] in which the functionality of the original gene is distributed among the two copies. Neither gene can be lost, as both now perform important non-redundant functions, but ultimately neither is able to achieve novel functionality.

Subfunctionalization can occur through neutral processes in which mutations accumulate with no detrimental or beneficial effects. However, in some cases subfunctionalization can occur with clear adaptive benefits. If an ancestral gene is pleiotropic and performs two functions, often neither one of these two functions can be changed without affecting the other function. In this way, partitioning the ancestral functions into two separate genes can allow for adaptive specialization of subfunctions, thereby providing an adaptive benefit. [31]

Loss

Often the resulting genomic variation leads to gene dosage dependent neurological disorders such as Rett-like syndrome and Pelizaeus–Merzbacher disease. [32] Such detrimental mutations are likely to be lost from the population and will not be preserved or develop novel functions. However, many duplications are, in fact, not detrimental or beneficial, and these neutral sequences may be lost or may spread through the population through random fluctuations via genetic drift.

Identifying duplications in sequenced genomes

Criteria and single genome scans

The two genes that exist after a gene duplication event are called paralogs and usually code for proteins with a similar function and/or structure. By contrast, orthologous genes present in different species which are each originally derived from the same ancestral sequence. (See Homology of sequences in genetics).

It is important (but often difficult) to differentiate between paralogs and orthologs in biological research. Experiments on human gene function can often be carried out on other species if a homolog to a human gene can be found in the genome of that species, but only if the homolog is orthologous. If they are paralogs and resulted from a gene duplication event, their functions are likely to be too different. One or more copies of duplicated genes that constitute a gene family may be affected by insertion of transposable elements that causes significant variation between them in their sequence and finally may become responsible for divergent evolution. This may also render the chances and the rate of gene conversion between the homologs of gene duplicates due to less or no similarity in their sequences.

Paralogs can be identified in single genomes through a sequence comparison of all annotated gene models to one another. Such a comparison can be performed on translated amino acid sequences (e.g. BLASTp, tBLASTx) to identify ancient duplications or on DNA nucleotide sequences (e.g. BLASTn, megablast) to identify more recent duplications. Most studies to identify gene duplications require reciprocal-best-hits or fuzzy reciprocal-best-hits, where each paralog must be the other's single best match in a sequence comparison. [33]

Most gene duplications exist as low copy repeats (LCRs), rather highly repetitive sequences like transposable elements. They are mostly found in pericentronomic, subtelomeric and interstitial regions of a chromosome. Many LCRs, due to their size (>1Kb), similarity, and orientation, are highly susceptible to duplications and deletions.

Genomic microarrays detect duplications

Technologies such as genomic microarrays, also called array comparative genomic hybridization (array CGH), are used to detect chromosomal abnormalities, such as microduplications, in a high throughput fashion from genomic DNA samples. In particular, DNA microarray technology can simultaneously monitor the expression levels of thousands of genes across many treatments or experimental conditions, greatly facilitating the evolutionary studies of gene regulation after gene duplication or speciation. [34] [35]

Next generation sequencing

Gene duplications can also be identified through the use of next-generation sequencing platforms. The simplest means to identify duplications in genomic resequencing data is through the use of paired-end sequencing reads. Tandem duplications are indicated by sequencing read pairs which map in abnormal orientations. Through a combination of increased sequence coverage and abnormal mapping orientation, it is possible to identify duplications in genomic sequencing data.

Nomenclature

Human karyotype with annotated bands and sub-bands as used for the nomenclature of chromosome abnormalities. It shows dark and white regions as seen on G banding. Each row is vertically aligned at centromere level. It shows 22 homologous autosomal chromosome pairs, both the female (XX) and male (XY) versions of the two sex chromosomes, as well as the mitochondrial genome (at bottom left). Further information: Karyotype Human karyotype with bands and sub-bands.png
Human karyotype with annotated bands and sub-bands as used for the nomenclature of chromosome abnormalities. It shows dark and white regions as seen on G banding. Each row is vertically aligned at centromere level. It shows 22 homologous autosomal chromosome pairs, both the female (XX) and male (XY) versions of the two sex chromosomes, as well as the mitochondrial genome (at bottom left).

The International System for Human Cytogenomic Nomenclature (ISCN) is an international standard for human chromosome nomenclature, which includes band names, symbols and abbreviated terms used in the description of human chromosome and chromosome abnormalities. Abbreviations include dup for duplications of parts of a chromosome. [36] For example, dup(17p12) causes Charcot–Marie–Tooth disease type 1A. [37]

As amplification

Gene duplication does not necessarily constitute a lasting change in a species' genome. In fact, such changes often don't last past the initial host organism. From the perspective of molecular genetics, gene amplification is one of many ways in which a gene can be overexpressed. Genetic amplification can occur artificially, as with the use of the polymerase chain reaction technique to amplify short strands of DNA in vitro using enzymes, or it can occur naturally, as described above. If it's a natural duplication, it can still take place in a somatic cell, rather than a germline cell (which would be necessary for a lasting evolutionary change).

Role in cancer

Duplications of oncogenes are a common cause of many types of cancer. In such cases the genetic duplication occurs in a somatic cell and affects only the genome of the cancer cells themselves, not the entire organism, much less any subsequent offspring. Recent comprehensive patient-level classification and quantification of driver events in TCGA cohorts revealed that there are on average 12 driver events per tumor, of which 1.5 are amplifications of oncogenes. [38]

Common oncogene amplifications in human cancers
Cancer typeAssociated gene
amplifications		Prevalence of
amplification
in cancer type
(percent)
Breast cancer MYC 20% [39]
ERBB2 (HER2)20% [39]
CCND1 (Cyclin D1)15–20% [39]
FGFR1 12% [39]
FGFR2 12% [39]
Cervical cancer MYC 25–50% [39]
ERBB2 20% [39]
Colorectal cancer HRAS 30% [39]
KRAS 20% [39]
MYB 15–20% [39]
Esophageal cancer MYC 40% [39]
CCND1 25% [39]
MDM2 13% [39]
Gastric cancer CCNE (Cyclin E)15% [39]
KRAS 10% [39]
MET 10% [39]
Glioblastoma ERBB1 (EGFR)33–50% [39]
CDK4 15% [39]
Head and neck cancer CCND1 50% [39]
ERBB1 10% [39]
MYC 7–10% [39]
Hepatocellular cancer CCND1 13% [39]
Neuroblastoma MYCN 20–25% [39]
Ovarian cancer MYC 20–30% [39]
ERBB2 15–30% [39]
AKT2 12% [39]
Sarcoma MDM2 10–30% [39]
CDK4 10% [39]
Small cell lung cancer MYC 15–20% [39]


Whole-genome duplications are also frequent in cancers, detected in 30% to 36% of tumors from the most common cancer types. [40] [41] Their exact role in carcinogenesis is unclear, but they in some cases lead to loss of chromatin segregation leading to chromatin conformation changes that in turn lead to oncogenic epigenetic and transcriptional modifications. [42]

See also

Related Research Articles

<span class="mw-page-title-main">Genome</span> All genetic material of an organism

In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA. The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as regulatory sequences, and often a substantial fraction of junk DNA with no evident function. Almost all eukaryotes have mitochondria and a small mitochondrial genome. Algae and plants also contain chloroplasts with a chloroplast genome.

Microevolution is the change in allele frequencies that occurs over time within a population. This change is due to four different processes: mutation, selection, gene flow and genetic drift. This change happens over a relatively short amount of time compared to the changes termed macroevolution.

<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">Transposable element</span> Semiparasitic DNA sequence

A transposable element is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Transposition often results in duplication of the same genetic material. In the human genome, L1 and Alu elements are two examples. Barbara McClintock's discovery of them earned her a Nobel Prize in 1983. Its importance in personalized medicine is becoming increasingly relevant, as well as gaining more attention in data analytics given the difficulty of analysis in very high dimensional spaces.

<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.

A microsatellite is a tract of repetitive DNA in which certain DNA motifs are repeated, typically 5–50 times. Microsatellites occur at thousands of locations within an organism's genome. They have a higher mutation rate than other areas of DNA leading to high genetic diversity. Microsatellites are often referred to as short tandem repeats (STRs) by forensic geneticists and in genetic genealogy, or as simple sequence repeats (SSRs) by plant geneticists.

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, the evolution of development, and ways that evolutionary forces influence genomic and phenotypic changes.

<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 gene 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. Pseudogenes are a type of junk DNA.

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

Molecular genetics is a branch 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. 

<span class="mw-page-title-main">Comparative genomics</span>

Comparative genomics is a field of biological research in which the genomic features of different organisms are compared. The genomic features may include the DNA sequence, genes, gene order, regulatory sequences, and other genomic structural landmarks. In this branch of genomics, whole or large parts of genomes resulting from genome projects are compared to study basic biological similarities and differences as well as evolutionary relationships between organisms. The major principle of comparative genomics is that common features of two organisms will often be encoded within the DNA that is evolutionarily conserved between them. Therefore, comparative genomic approaches start with making some form of alignment of genome sequences and looking for orthologous sequences in the aligned genomes and checking to what extent those sequences are conserved. Based on these, genome and molecular evolution are inferred and this may in turn be put in the context of, for example, phenotypic evolution or population genetics.

<span class="mw-page-title-main">Sequence homology</span> Shared ancestry between DNA, RNA or protein sequences

Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a speciation event (orthologs), or a duplication event (paralogs), or else a horizontal gene transfer event (xenologs).

<span class="mw-page-title-main">Paleopolyploidy</span> State of having undergone whole genome duplication in deep evolutionary time

Paleopolyploidy is the result of genome duplications which occurred at least several million years ago (MYA). Such an event could either double the genome of a single species (autopolyploidy) or combine those of two species (allopolyploidy). Because of functional redundancy, genes are rapidly silenced or lost from the duplicated genomes. Most paleopolyploids, through evolutionary time, have lost their polyploid status through a process called diploidization, and are currently considered diploids, e.g., baker's yeast, Arabidopsis thaliana, and perhaps humans.

<span class="mw-page-title-main">Copy number variation</span> Repeated DNA variation between individuals

Copy number variation (CNV) is a phenomenon in which sections of the genome are repeated and the number of repeats in the genome varies between individuals. Copy number variation is a type of structural variation: specifically, it is a type of duplication or deletion event that affects a considerable number of base pairs. Approximately two-thirds of the entire human genome may be composed of repeats and 4.8–9.5% of the human genome can be classified as copy number variations. In mammals, copy number variations play an important role in generating necessary variation in the population as well as disease phenotype.

<span class="mw-page-title-main">Gene</span> Sequence of DNA or RNA that codes for an RNA or protein product

In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. 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 non-coding genes.

<span class="mw-page-title-main">Gene cluster</span>

A gene family is a set of homologous genes within one organism. A gene cluster is a group of two or more genes found within an organism's DNA that encode similar polypeptides, or proteins, which collectively share a generalized function and are often located within a few thousand base pairs of each other. The size of gene clusters can vary significantly, from a few genes to several hundred genes. Portions of the DNA sequence of each gene within a gene cluster are found to be identical; however, the resulting protein of each gene is distinctive from the resulting protein of another gene within the cluster. Genes found in a gene cluster may be observed near one another on the same chromosome or on different, but homologous chromosomes. An example of a gene cluster is the Hox gene, which is made up of eight genes and is part of the Homeobox gene family.

NUMT, pronounced "new might", is an acronym for "nuclear mitochondrial DNA" segment or genetic locus coined by evolutionary geneticist, Jose V. Lopez, which describes a transposition of any type of cytoplasmic mitochondrial DNA into the nuclear genome of eukaryotic organisms.

<span class="mw-page-title-main">Gene redundancy</span>

Gene redundancy is the existence of multiple genes in the genome of an organism that perform the same function. Gene redundancy can result from gene duplication. Such duplication events are responsible for many sets of paralogous genes. When an individual gene in such a set is disrupted by mutation or targeted knockout, there can be little effect on phenotype as a result of gene redundancy, whereas the effect is large for the knockout of a gene with only one copy. Gene knockout is a method utilized in some studies aiming to characterize the maintenance and fitness effects functional overlap.

<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.

<span class="mw-page-title-main">Unequal crossing over</span> Chromosomal crossover resulting in gene duplication or deletion

Unequal crossing over is a type of gene duplication or deletion event that deletes a sequence in one strand and replaces it with a duplication from its sister chromatid in mitosis or from its homologous chromosome during meiosis. It is a type of chromosomal crossover between homologous sequences that are not paired precisely. Normally genes are responsible for occurrence of crossing over. It exchanges sequences of different links between chromosomes. Along with gene conversion, it is believed to be the main driver for the generation of gene duplications and is a source of mutation in the genome.

DNA transposons are DNA sequences, sometimes referred to "jumping genes", that can move and integrate to different locations within the genome. They are class II transposable elements (TEs) that move through a DNA intermediate, as opposed to class I TEs, retrotransposons, that move through an RNA intermediate. DNA transposons can move in the DNA of an organism via a single-or double-stranded DNA intermediate. DNA transposons have been found in both prokaryotic and eukaryotic organisms. They can make up a significant portion of an organism's genome, particularly in eukaryotes. In prokaryotes, TE's can facilitate the horizontal transfer of antibiotic resistance or other genes associated with virulence. After replicating and propagating in a host, all transposon copies become inactivated and are lost unless the transposon passes to a genome by starting a new life cycle with horizontal transfer. It is important to note that DNA transposons do not randomly insert themselves into the genome, but rather show preference for specific sites.

References

  1. ↑ Zhang J (2003). "Evolution by gene duplication: an update" (PDF). Trends in Ecology & Evolution. 18 (6): 292–8. doi:10.1016/S0169-5347(03)00033-8.
  2. ↑ "Definition of Gene duplication". medterms medical dictionary. MedicineNet. 2012-03-19.
  3. ↑ Miller, Duncan; Chen, Jianhai; Liang, Jiangtao; Betrán, Esther; Long, Manyuan; Sharakhov, Igor V. (2022-05-28). "Retrogene Duplication and Expression Patterns Shaped by the Evolution of Sex Chromosomes in Malaria Mosquitoes". Genes. 13 (6): 968. doi: 10.3390/genes13060968 . ISSN   2073-4425. PMC   9222922 . PMID   35741730.
  4. ↑ Dehal P, Boore JL (October 2005). "Two rounds of whole genome duplication in the ancestral vertebrate". PLOS Biology. 3 (10): e314. doi: 10.1371/journal.pbio.0030314 . PMC   1197285 . PMID   16128622.
  5. ↑ Wolfe, K. H.; Shields, D. C. (1997-06-12). "Molecular evidence for an ancient duplication of the entire yeast genome". Nature. 387 (6634): 708–713. Bibcode:1997Natur.387..708W. doi: 10.1038/42711 . ISSN   0028-0836. PMID   9192896. S2CID   4307263.
  6. ↑ Kellis, Manolis; Birren, Bruce W.; Lander, Eric S. (2004-04-08). "Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae". Nature. 428 (6983): 617–624. Bibcode:2004Natur.428..617K. doi:10.1038/nature02424. ISSN   1476-4687. PMID   15004568. S2CID   4422074.
  7. ↑ Otto, Sarah P. (2007-11-02). "The evolutionary consequences of polyploidy". Cell. 131 (3): 452–462. doi: 10.1016/j.cell.2007.10.022 . ISSN   0092-8674. PMID   17981114. S2CID   10054182.
  8. ↑ Conant, Gavin C.; Wolfe, Kenneth H. (April 2006). "Functional partitioning of yeast co-expression networks after genome duplication". PLOS Biology. 4 (4): e109. doi: 10.1371/journal.pbio.0040109 . ISSN   1545-7885. PMC   1420641 . PMID   16555924.
  9. ↑ Papp, Balázs; Pál, Csaba; Hurst, Laurence D. (2003-07-10). "Dosage sensitivity and the evolution of gene families in yeast". Nature. 424 (6945): 194–197. Bibcode:2003Natur.424..194P. doi:10.1038/nature01771. ISSN   1476-4687. PMID   12853957. S2CID   4382441.
  10. ↑ Lynch, M.; Conery, J. S. (2000-11-10). "The evolutionary fate and consequences of duplicate genes". Science. 290 (5494): 1151–1155. Bibcode:2000Sci...290.1151L. doi:10.1126/science.290.5494.1151. ISSN   0036-8075. PMID   11073452.
  11. ↑ Freeling, Michael; Thomas, Brian C. (July 2006). "Gene-balanced duplications, like tetraploidy, provide predictable drive to increase morphological complexity". Genome Research. 16 (7): 805–814. doi: 10.1101/gr.3681406 . ISSN   1088-9051. PMID   16818725.
  12. ↑ Davis, Jerel C.; Petrov, Dmitri A. (October 2005). "Do disparate mechanisms of duplication add similar genes to the genome?". Trends in Genetics. 21 (10): 548–551. doi:10.1016/j.tig.2005.07.008. ISSN   0168-9525. PMID   16098632.
  13. ↑ Casneuf, Tineke; De Bodt, Stefanie; Raes, Jeroen; Maere, Steven; Van de Peer, Yves (2006). "Nonrandom divergence of gene expression following gene and genome duplications in the flowering plant Arabidopsis thaliana". Genome Biology. 7 (2): R13. doi: 10.1186/gb-2006-7-2-r13 . ISSN   1474-760X. PMC   1431724 . PMID   16507168.
  14. ↑ Li, Wen-Hsiung; Yang, Jing; Gu, Xun (November 2005). "Expression divergence between duplicate genes". Trends in Genetics. 21 (11): 602–607. doi:10.1016/j.tig.2005.08.006. ISSN   0168-9525. PMID   16140417.
  15. 1 2 Amoutzias, Grigoris D.; He, Ying; Gordon, Jonathan; Mossialos, Dimitris; Oliver, Stephen G.; Van de Peer, Yves (2010-02-16). "Posttranslational regulation impacts the fate of duplicated genes". Proceedings of the National Academy of Sciences of the United States of America. 107 (7): 2967–2971. Bibcode:2010PNAS..107.2967A. doi: 10.1073/pnas.0911603107 . ISSN   1091-6490. PMC   2840353 . PMID   20080574.
  16. ↑ Sebat J, Lakshmi B, Troge J, Alexander J, Young J, Lundin P, et al. (July 2004). "Large-scale copy number polymorphism in the human genome". Science. 305 (5683): 525–8. Bibcode:2004Sci...305..525S. doi:10.1126/science.1098918. PMID   15273396. S2CID   20357402.
  17. ↑ Iafrate AJ, Feuk L, Rivera MN, Listewnik ML, Donahoe PK, Qi Y, et al. (September 2004). "Detection of large-scale variation in the human genome". Nature Genetics. 36 (9): 949–51. doi: 10.1038/ng1416 . PMID   15286789.
  18. ↑ Emerson JJ, Cardoso-Moreira M, Borevitz JO, Long M (June 2008). "Natural selection shapes genome-wide patterns of copy-number polymorphism in Drosophila melanogaster". Science. 320 (5883): 1629–31. Bibcode:2008Sci...320.1629E. doi:10.1126/science.1158078. PMID   18535209. S2CID   206512885.
  19. ↑ Lipinski KJ, Farslow JC, Fitzpatrick KA, Lynch M, Katju V, Bergthorsson U (February 2011). "High spontaneous rate of gene duplication in Caenorhabditis elegans". Current Biology. 21 (4): 306–10. doi:10.1016/j.cub.2011.01.026. PMC   3056611 . PMID   21295484.
  20. ↑ Anderson P, Roth J (May 1981). "Spontaneous tandem genetic duplications in Salmonella typhimurium arise by unequal recombination between rRNA (rrn) cistrons". Proceedings of the National Academy of Sciences of the United States of America. 78 (5): 3113–7. Bibcode:1981PNAS...78.3113A. doi: 10.1073/pnas.78.5.3113 . PMC   319510 . PMID   6789329.
  21. ↑ Watanabe Y, Takahashi A, Itoh M, Takano-Shimizu T (March 2009). "Molecular spectrum of spontaneous de novo mutations in male and female germline cells of Drosophila melanogaster". Genetics. 181 (3): 1035–43. doi:10.1534/genetics.108.093385. PMC   2651040 . PMID   19114461.
  22. ↑ Turner DJ, Miretti M, Rajan D, Fiegler H, Carter NP, Blayney ML, et al. (January 2008). "Germline rates of de novo meiotic deletions and duplications causing several genomic disorders". Nature Genetics. 40 (1): 90–5. doi:10.1038/ng.2007.40. PMC   2669897 . PMID   18059269.
  23. ↑ Lynch VJ (January 2007). "Inventing an arsenal: adaptive evolution and neofunctionalization of snake venom phospholipase A2 genes". BMC Evolutionary Biology. 7: 2. doi: 10.1186/1471-2148-7-2 . PMC   1783844 . PMID   17233905.
  24. ↑ Conant GC, Wolfe KH (December 2008). "Turning a hobby into a job: how duplicated genes find new functions". Nature Reviews. Genetics. 9 (12): 938–50. doi:10.1038/nrg2482. PMID   19015656. S2CID   1240225.
  25. ↑ Taylor JS, Raes J (2004). "Duplication and divergence: the evolution of new genes and old ideas". Annual Review of Genetics. 38: 615–43. doi:10.1146/annurev.genet.38.072902.092831. PMID   15568988.
  26. ↑ Ohno, S. (1970). Evolution by gene duplication. Springer-Verlag. ISBN   978-0-04-575015-3.
  27. ↑ Ohno, S. (1967). Sex Chromosomes and Sex-linked Genes . Springer-Verlag. ISBN   978-91-554-5776-1.
  28. ↑ Kellis M, Birren BW, Lander ES (April 2004). "Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae". Nature. 428 (6983): 617–24. Bibcode:2004Natur.428..617K. doi:10.1038/nature02424. PMID   15004568. S2CID   4422074.
  29. ↑ Force A, Lynch M, Pickett FB, Amores A, Yan YL, Postlethwait J (April 1999). "Preservation of duplicate genes by complementary, degenerative mutations". Genetics. 151 (4): 1531–45. doi:10.1093/genetics/151.4.1531. PMC   1460548 . PMID   10101175.
  30. ↑ Stoltzfus A (August 1999). "On the possibility of constructive neutral evolution". Journal of Molecular Evolution. 49 (2): 169–81. Bibcode:1999JMolE..49..169S. CiteSeerX   10.1.1.466.5042 . doi:10.1007/PL00006540. PMID   10441669. S2CID   1743092.
  31. ↑ Des Marais DL, Rausher MD (August 2008). "Escape from adaptive conflict after duplication in an anthocyanin pathway gene". Nature. 454 (7205): 762–5. Bibcode:2008Natur.454..762D. doi:10.1038/nature07092. PMID   18594508. S2CID   418964.
  32. ↑ Lee JA, Lupski JR (October 2006). "Genomic rearrangements and gene copy-number alterations as a cause of nervous system disorders". Neuron. 52 (1): 103–21. doi: 10.1016/j.neuron.2006.09.027 . PMID   17015230. S2CID   22412305.
  33. ↑ Hahn MW, Han MV, Han SG (November 2007). "Gene family evolution across 12 Drosophila genomes". PLOS Genetics. 3 (11): e197. doi: 10.1371/journal.pgen.0030197 . PMC   2065885 . PMID   17997610.
  34. ↑ Mao R, Pevsner J (2005). "The use of genomic microarrays to study chromosomal abnormalities in mental retardation". Mental Retardation and Developmental Disabilities Research Reviews. 11 (4): 279–85. doi:10.1002/mrdd.20082. PMID   16240409.
  35. ↑ Gu X, Zhang Z, Huang W (January 2005). "Rapid evolution of expression and regulatory divergences after yeast gene duplication". Proceedings of the National Academy of Sciences of the United States of America. 102 (3): 707–12. Bibcode:2005PNAS..102..707G. doi: 10.1073/pnas.0409186102 . PMC   545572 . PMID   15647348.
  36. ↑ "ISCN Symbols and Abbreviated Terms". Coriell Institute for Medical Research. Retrieved 2022-10-27.
  37. ↑ Cassandra L. Kniffin. "HARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 1A; CMT1A". OMIM . Updated : 4/23/2014
  38. ↑ Vyatkin, Alexey D.; Otnyukov, Danila V.; Leonov, Sergey V.; Belikov, Aleksey V. (14 January 2022). "Comprehensive patient-level classification and quantification of driver events in TCGA PanCanAtlas cohorts". PLOS Genetics. 18 (1): e1009996. doi: 10.1371/journal.pgen.1009996 . PMC   8759692 . PMID   35030162.
  39. 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 Kinzler KW, Vogelstein B (2002). The genetic basis of human cancer. McGraw-Hill. p. 116. ISBN   978-0-07-137050-9.
  40. ↑ Bielski, Craig M.; Zehir, Ahmet; Penson, Alexander V.; Donoghue, Mark T. A.; Chatila, Walid; Armenia, Joshua; Chang, Matthew T.; Schram, Alison M.; Jonsson, Philip; Bandlamudi, Chaitanya; Razavi, Pedram; Iyer, Gopa; Robson, Mark E.; Stadler, Zsofia K.; Schultz, Nikolaus (2018). "Genome doubling shapes the evolution and prognosis of advanced cancers". Nature Genetics. 50 (8): 1189–1195. doi:10.1038/s41588-018-0165-1. ISSN   1546-1718. PMC   6072608 . PMID   30013179.
  41. ↑ Quinton, Ryan J.; DiDomizio, Amanda; Vittoria, Marc A.; Kotýnková, Kristýna; Ticas, Carlos J.; Patel, Sheena; Koga, Yusuke; Vakhshoorzadeh, Jasmine; Hermance, Nicole; Kuroda, Taruho S.; Parulekar, Neha; Taylor, Alison M.; Manning, Amity L.; Campbell, Joshua D.; Ganem, Neil J. (2021). "Whole-genome doubling confers unique genetic vulnerabilities on tumour cells". Nature. 590 (7846): 492–497. Bibcode:2021Natur.590..492Q. doi:10.1038/s41586-020-03133-3. ISSN   1476-4687. PMC   7889737 . PMID   33505027.
  42. ↑ Lambuta, Ruxandra A.; Nanni, Luca; Liu, Yuanlong; Diaz-Miyar, Juan; Iyer, Arvind; Tavernari, Daniele; Katanayeva, Natalya; Ciriello, Giovanni; Oricchio, Elisa (2023-03-15). "Whole-genome doubling drives oncogenic loss of chromatin segregation". Nature. 615 (7954): 925–933. Bibcode:2023Natur.615..925L. doi: 10.1038/s41586-023-05794-2 . ISSN   1476-4687. PMC   10060163 . PMID   36922594.
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