Gallery
- The human nuclear DNA displayed into chromosome ideograms with label from Human Genome Project (1990-2003)
Nuclear DNA (nDNA), or nuclear deoxyribonucleic acid, is the DNA contained within each cell nucleus of a eukaryotic organism. [1] It encodes for the majority of the genome in eukaryotes, with mitochondrial DNA and plastid DNA coding for the rest. It adheres to Mendelian inheritance, with information coming from two parents, one male and one female—rather than matrilineally (through the mother) as in mitochondrial DNA. [2]
Nuclear DNA is a nucleic acid, a polymeric biomolecule or biopolymer, found in the nucleus of eukaryotic cells. Its structure is a double helix, with two strands wound around each other, a structure first described by Francis Crick and James D. Watson (1953) using data collected by Rosalind Franklin. Each strand is a long polymer chain of repeating nucleotides. [3] Each nucleotide is composed of a five-carbon sugar, a phosphate group, and an organic base. Nucleotides are distinguished by their bases: purines, large bases that include adenine and guanine; and pyrimidines, small bases that include thymine and cytosine. Chargaff's rules state that adenine always pairs with thymine, and guanine always with cytosine. The phosphate groups are held together by a phosphodiester bond and the bases are held together by hydrogen bonds. [4]
Nuclear DNA and mitochondrial DNA differ in many ways, starting with location and structure. Nuclear DNA is located within the nucleus of eukaryote cells and usually has two copies per cell while mitochondrial DNA is located in the mitochondria and contains 100–1,000 copies per cell. The structure of nuclear DNA chromosomes is linear with open ends and includes 46 chromosomes and contains for example 3 billion nucleotides in humans while the structure of Mitochondrial DNA chromosome is usually closed, circular, and contains for example 16,569 nucleotides in humans. [5] Nuclear DNA in animals is diploid, ordinarily inheriting the DNA from two parents, while mitochondrial DNA is haploid, coming only from the mother. The mutation rate for nuclear DNA is less than 0.3% while that of mitochondrial DNA is generally higher. [6]
Nuclear DNA is known as the molecule of life and contains the genetic instructions for the development of all eukaryotic organisms. It is found in almost every cell in the human body, with exceptions such as red blood cells. Everyone has a unique genetic blueprint, even identical twins. [7] Forensic departments such as the Bureau of Criminal Apprehension (BCA) and Federal Bureau of Investigation (FBI) are able to use techniques involving nuclear DNA to compare samples in a case. Techniques used include polymerase chain reaction (PCR), which allows one to utilize very small amounts of DNA by making copies of targeted regions on the molecule, also known as short tandem repeats (STRs). [8] [9]
Like mitosis, meiosis is a form of eukaryotic cell division. Meiosis gives rise to four unique daughter cells, each of which has half the number of chromosomes as the parent cell. Because meiosis creates cells that are destined to become gametes (or reproductive cells), this reduction in chromosome number is critical — without it, the union of two gametes during fertilization would result in offspring with twice the normal number of chromosomes.
Meiosis creates new combinations of genetic material in each of the four daughter cells. These new combinations result from the exchange of DNA between paired chromosomes. Such an exchange means that the gametes produced through meiosis often exhibit considerable genetic variation.
Meiosis involves two rounds of nuclear division, not just one. Prior to undergoing meiosis, a cell goes through an interphase period in which it grows, replicates its chromosomes, and checks all of its systems to ensure that it is ready to divide.
Like mitosis, meiosis also has distinct stages called prophase, metaphase, anaphase, and telophase. A key difference, however, is that during meiosis, each of these phases occurs twice — once during the first round of division, called meiosis I, and again during the second round of division, called meiosis II. [10]
Prior to cell division, the DNA material in the original cell must be duplicated so that after cell division, each new cell contains the full amount of DNA material. The process of DNA duplication is usually called replication. The replication is termed semiconservative since each new cell contains one strand of original DNA and one newly synthesized strand of DNA. The original polynucleotide strand of DNA serves as a template to guide the synthesis of the new complementary polynucleotide of DNA. The DNA single-strand template serves to guide the synthesis of a complementary strand of DNA. [11]
DNA replication begins at a specific site in the DNA molecule called the origin of replication. The enzyme helicase unwinds and separates a portion of the DNA molecule after which single-strand binding proteins react with and stabilize the separated, single-stranded sections of the DNA molecule. The enzyme complex DNA polymerase engages the separated portion of the molecule and initiates the process of replication. DNA polymerase can only connect new DNA nucleotides to a pre-existing chain of nucleotides. Therefore, replication begins as an enzyme called primase assembles an RNA primer at the origin of replication. The RNA primer consists of a short sequence of RNA nucleotides, complementary to a small, initial section of the DNA strand being prepared for replication. DNA polymerase is then able to add DNA nucleotides to the RNA primer and thus begin the process of constructing a new complementary strand of DNA. Later the RNA primer is enzymatically removed and replaced with the appropriate sequence of DNA nucleotides. Because the two complementary strands of the DNA molecule are oriented in opposite directions and the DNA polymerase can only accommodate replication in one direction, two different mechanisms for copying the strands of DNA are employed. One strand is replicated continuously towards unwinding, separating the portion of the original DNA molecule; while the other strand is replicated discontinuously in the opposite direction with the formation of a series of short DNA segments called Okazaki fragments. Each Okazaki fragment requires a separate RNA primer. As the Okazaki fragments are synthesized, the RNA primers are replaced with DNA nucleotides and the fragments are bonded together in a continuous complementary strand. [12]
Damage of nuclear DNA is a persistent problem arising from a variety of disruptive endogenous and exogenous sources. Eukaryotes have evolved a diverse set of DNA repair processes that remove nuclear DNA damages. These repair processes include base excision repair, nucleotide excision repair, homologous recombinational repair, non-homologous end joining and microhomology-mediated end joining. Such repair processes are essential for maintaining nuclear DNA stability. Failure of repair activity to keep up with the occurrence of damages has various negative consequences. Nuclear DNA damages, as well as the mutations and epigenetic alterations that such damages cause, are considered to be a major cause of cancer.[ citation needed ] Nuclear DNA damages are also implicated in aging [13] and neurodegenerative diseases. [14] [15]
Nuclear DNA is subject to mutation. A major cause of mutation is inaccurate DNA replication, often by specialized DNA polymerases that synthesize past DNA damages in the template strand (error-prone trans-lesion synthesis). [16] Mutations also arise by inaccurate DNA repair. The microhomology-mediated end joining pathway for repair of double-strand breaks is particularly prone to mutation. [17] Mutations arising in the nuclear DNA of the germline are most often neutral or adaptively disadvantageous. However, the small proportion of mutations that prove to be advantageous provide the genetic variation upon which natural selection operates to generate new adaptations.
Deoxyribonucleic acid is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses. DNA and ribonucleic acid (RNA) are nucleic acids. Alongside proteins, lipids and complex carbohydrates (polysaccharides), nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life.
In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part of biological inheritance. This is essential for cell division during growth and repair of damaged tissues, while it also ensures that each of the new cells receives its own copy of the DNA. The cell possesses the distinctive property of division, which makes replication of DNA essential.
A primer is a short single-stranded nucleic acid used by all living organisms in the initiation of DNA synthesis. DNA polymerase enzymes are only capable of adding nucleotides to the 3’-end of an existing nucleic acid, requiring a primer be bound to the template before DNA polymerase can begin a complementary strand. DNA polymerase adds nucleotides after binding to the RNA primer and synthesizes the whole strand. Later, the RNA strands must be removed accurately and replace them with DNA nucleotides forming a gap region known as a nick that is filled in using an enzyme called ligase. The removal process of the RNA primer requires several enzymes, such as Fen1, Lig1, and others that work in coordination with DNA polymerase, to ensure the removal of the RNA nucleotides and the addition of DNA nucleotides. Living organisms use solely RNA primers, while laboratory techniques in biochemistry and molecular biology that require in vitro DNA synthesis usually use DNA primers, since they are more temperature stable. Primers can be designed in laboratory for specific reactions such as polymerase chain reaction (PCR). When designing PCR primers, there are specific measures that must be taken into consideration, like the melting temperature of the primers and the annealing temperature of the reaction itself. Moreover, the DNA binding sequence of the primer in vitro has to be specifically chosen, which is done using a method called basic local alignment search tool (BLAST) that scans the DNA and finds specific and unique regions for the primer to bind.
A reverse transcriptase (RT) is an enzyme used to generate complementary DNA (cDNA) from an RNA template, a process termed reverse transcription. Reverse transcriptases are used by viruses such as HIV and hepatitis B to replicate their genomes, by retrotransposon mobile genetic elements to proliferate within the host genome, and by eukaryotic cells to extend the telomeres at the ends of their linear chromosomes. Contrary to a widely held belief, the process does not violate the flows of genetic information as described by the classical central dogma, as transfers of information from RNA to DNA are explicitly held possible.
Genetic recombination is the exchange of genetic material between different organisms which leads to production of offspring with combinations of traits that differ from those found in either parent. In eukaryotes, genetic recombination during meiosis can lead to a novel set of genetic information that can be further passed on from parents to offspring. Most recombination occurs naturally and can be classified into two types: (1) interchromosomal recombination, occurring through independent assortment of alleles whose loci are on different but homologous chromosomes ; & (2) intrachromosomal recombination, occurring through crossing over.
A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create two identical DNA duplexes from a single original DNA duplex. During this process, DNA polymerase "reads" the existing DNA strands to create two new strands that match the existing ones. These enzymes catalyze the chemical reaction
DNA synthesis is the natural or artificial creation of deoxyribonucleic acid (DNA) molecules. DNA is a macromolecule made up of nucleotide units, which are linked by covalent bonds and hydrogen bonds, in a repeating structure. DNA synthesis occurs when these nucleotide units are joined to form DNA; this can occur artificially or naturally. Nucleotide units are made up of a nitrogenous base, pentose sugar (deoxyribose) and phosphate group. Each unit is joined when a covalent bond forms between its phosphate group and the pentose sugar of the next nucleotide, forming a sugar-phosphate backbone. DNA is a complementary, double stranded structure as specific base pairing occurs naturally when hydrogen bonds form between the nucleotide bases.
A nuclease is an enzyme capable of cleaving the phosphodiester bonds between nucleotides of nucleic acids. Nucleases variously effect single and double stranded breaks in their target molecules. In living organisms, they are essential machinery for many aspects of DNA repair. Defects in certain nucleases can cause genetic instability or immunodeficiency. Nucleases are also extensively used in molecular cloning.
DNA polymerase I is an enzyme that participates in the process of prokaryotic DNA replication. Discovered by Arthur Kornberg in 1956, it was the first known DNA polymerase. It was initially characterized in E. coli and is ubiquitous in prokaryotes. In E. coli and many other bacteria, the gene that encodes Pol I is known as polA. The E. coli Pol I enzyme is composed of 928 amino acids, and is an example of a processive enzyme — it can sequentially catalyze multiple polymerisation steps without releasing the single-stranded template. The physiological function of Pol I is mainly to support repair of damaged DNA, but it also contributes to connecting Okazaki fragments by deleting RNA primers and replacing the ribonucleotides with DNA.
Okazaki fragments are short sequences of DNA nucleotides which are synthesized discontinuously and later linked together by the enzyme DNA ligase to create the lagging strand during DNA replication. They were discovered in the 1960s by the Japanese molecular biologists Reiji and Tsuneko Okazaki, along with the help of some of their colleagues.
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encodes its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in tens of thousands of individual molecular lesions per cell per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur, including double-strand breaks and DNA crosslinkages. This can eventually lead to malignant tumors, or cancer as per the two hit hypothesis.
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.
In biology, the word gene 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.
The replisome is a complex molecular machine that carries out replication of DNA. The replisome first unwinds double stranded DNA into two single strands. For each of the resulting single strands, a new complementary sequence of DNA is synthesized. The total result is formation of two new double stranded DNA sequences that are exact copies of the original double stranded DNA sequence.
Eukaryotic DNA replication is a conserved mechanism that restricts DNA replication to once per cell cycle. Eukaryotic DNA replication of chromosomal DNA is central for the duplication of a cell and is necessary for the maintenance of the eukaryotic genome.
A primer binding site is a region of a nucleotide sequence where an RNA or DNA single-stranded primer binds to start replication. The primer binding site is on one of the two complementary strands of a double-stranded nucleotide polymer, in the strand which is to be copied, or is within a single-stranded nucleotide polymer sequence.
The origin and function of meiosis are currently not well understood scientifically, and would provide fundamental insight into the evolution of sexual reproduction in eukaryotes. There is no current consensus among biologists on the questions of how sex in eukaryotes arose in evolution, what basic function sexual reproduction serves, and why it is maintained, given the basic two-fold cost of sex. It is clear that it evolved over 1.2 billion years ago, and that almost all species which are descendants of the original sexually reproducing species are still sexual reproducers, including plants, fungi, and animals.
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.
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 split across two articles:
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| Ribonucleic acids (coding, non-coding) |
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| Deoxyribonucleic acids | |||||||
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| Cloning vectors | |||||||
