Deoxyribonucleic acid

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Definition

noun

(uncountable)

de·oxy·ri·bo·nu·cle·ic ac·id, [diˈɒksɪraɪboʊnjuːkliːɪk ˈæsɪd]


A nucleic acid that generally is double-stranded and helical, and a crucial biomolecule for containing the genetic information for cell growth, division, and function


Details

Overview

A nucleic acid refers to any of the group of complex compounds made up of linear chains of monomeric nucleotides. Each nucleotide component, in turn, is made up of phosphoric acid, sugar, and nitrogenous base. Nucleic acids are involved in the preservation, replication, and expression of hereditary information. Two major types of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).


History and terminology

Swiss physician and biologist, Friedrich Miescher [1844 –1895], was the first to isolate DNA from the pus of discarded bandages. The then-novel biological molecule was neither a protein, nor a carbohydrate, nor a lipid from the nuclei of white blood cells. He named the compound nuclein from where he was able to isolate it from.[1] The acidic properties of the compound were discovered by the German chemist, Albrecht Kossel [1853 –1927]. He was also known to be the first to identify the nucleobases: adenine, cytosine, guanine, thymine, and uracil. Later, nuclein was replaced with nucleic acid; the term was coined in 1889by the German pathologist, Richard Altmann [1852 –1900].[2] The nuclein discovered by Miescher was later particularly identified as DNA. The double helical model of DNA was attributed to the joined effort of molecular biologists James Watson (American) and Francis Crick (British) in 1953. Their double-helical DNA model was based largely on the information that nucleobases were paired and on the X-ray diffraction image (referred to as Photo 51) by Rosalind Franklin [1920 – 1958] and Raymond Gosling in1952. Francis Crick was also known for his laying out of the central dogma of molecular biology. His central dogma depicts the relationship between the nucleic acids DNA and RNA, and proteins. With it, Crick showed how the information would be irreversibly transferred from nucleic acids to proteins. Furthermore, he and his colleagues suggested that the genetic code was read according to codons where each codon consisted of three nucleobases. Indian-American biochemist Har Gobind Khorana [1922 –2011], American biochemist Robert William Holley [1922 –1993], and Jewish American biochemist and geneticist Marshall Warren Nirenberg [1927 –2010] were able to decipher the genetic code and its relevance in protein synthesis.[3] In 1944, Oswald Avery, Colin MacLeod, and Maclyn McCarty's experiment helped set the DNA as the genetic material, which during their time it was largely believed to be protein.


Structure

DNA is a polynucleotide as it is made up of several monomeric units of nucleotides covalently bonded by 3', 5' phosphodiester linkages. This means that the 5'-phosphoric group of one nucleotide is esterified with the 3'-hydroxyl of the adjoining nucleotide. Each nucleotide, in turn, is comprised of phosphoric acid, a deoxyribose sugar (5-carbon), and a nitrogenous base. The nitrogenous base or nucleobase may be a cytosine [C], guanine [G],adenine [A] or thymine [T]. The two strands that make up the DNA form a helical structure wherein at the core the nucleobases are complementarily paired. The base pairing rules are adenine pairs with thymine whereas cytosine pairs with guanine. The bond that joins the two nucleobases is hydrogen bond. The two strands are antiparallel, which means they run in opposite directions to each other.

DNA molecule has two regions: the coding region and the non-coding region. The non-coding region, as the name implies, is the section of the DNA that does not code for a protein. In eukaryotic cell, DNA is organized into a chromosome inside the nucleus. The DNA inside the nucleus is compacted by chromatin proteins (e.g. histones). Some of the DNAs are stored in mitochondria (referred to as mitochondrial DNA, mtDNA) and chloroplast (referred to as chloroplast DNA, cpDNA). In prokaryotic cell, DNAs are found in a special region in the cytoplasm called nucleoid.


DNA vs RNA

DNA is a double-stranded nucleic acid containing the genetic information of a living thing. It is essential for the cell growth, division, and function of an organism. RNA is a single-stranded nucleic acid except for some viral RNAs and siRNA that are double-stranded. Below is a table that summarizes the major differences between DNA and RNA.


DNA RNA
Structure DNA is composed of two strands that twist together to form a helix, forming a ladder-like structure. Each strand consists of alternating phosphate (PO4) and pentose sugar (2-deoxyribose), and attached on the sugar is a nitrogenous base, which can be adenine, thymine, guanine, or cytosine. In DNA, adenine pairs with thymine and guanine with cytosine. Not all DNAs are double-stranded. For instance, a group of viruses have single-stranded DNA genome. RNA consists of a long linear chain of nucleotides. Each nucleotide unit is comprised of a sugar, a phosphate group and a nitrogenous base. It differs from DNA in having ribose as its sugar, (deoxyribose in DNA) and the bases are adenine, guanine, cytosine, and uracil. In RNA, adenine pairs with uracil and guanine with cytosine. RNAs are single-stranded except for certain viruses whose genome consists of double-stranded RNA.
Location In eukaryotes, most DNAs are located in the nucleoli and chromosomes in the nucleus. A small fraction of the total DNA is present in mitochondria, chloroplasts, and cytoplasm. In prokaryotes and viruses, DNA is found in the cytoplasm. In eukaryotes, RNA is found in the nucleus and in the cytoplasm. In prokaryotes and viruses, it is found in the cytoplasm.
Function DNA is a long polymer of nucleotides to code for the sequence of amino acid during protein synthesis. DNA carries the genetic ‘blueprint’ since it contains the instructions or information (called genes) needed to construct cellular components like proteins and RNAs. In some viruses, RNA is the genetic material. For most organisms, RNAs are involved in: protein synthesis (e.g. mRNA, tRNA, rRNA, etc.), post-transcriptional modification or DNA replication (e.g. snRNA, snoRNA, etc.), and gene regulation (e.g. miRNA, siRNA, tasiRNA, etc.).


One of the possible explanations why DNA has thymine instead of uracil is associated with the conversion of cytosine into uracil by spontaneous deamination. Cytosine can turn into uracil when it loses its amine group. This deamination of cytosine is a common occurrence. Nevertheless, the error is corrected through an inherent DNA repair systems. If not repaired though, it could lead to point mutation. If uracil is present in the DNA, the repair systems may not be able to distinguish the original uracil from the cytosine-turned-uracil and therefore may fail to discern which uracil to correct. The presence of methyl group in thymine (which is absent in uracil) helps avert this from happening, thereby, preserving the integrity and stability of the genetic code.


Prokaryotic DNA vs Eukaryotic DNA

Prokaryotic DNA Eukaryotic (nuclear) DNA
Structure Often circular and naked, meaning it is not bound with proteins

Compact genomes, with little repetitive DNA but without introns

Bound with proteins (e.g. histones) and therefore forms chromatin

Genomes with many non-coding and repetitive DNA sequences (including introns)

Location Found in the cytoplasmic region called the nucleoid Located inside the nucleus
Plasmid With extra-chromosomal plasmids No plasmids


Nuclear DNA vs. Extranuclear DNA

DNA outside the nucleus is referred to as extranuclear DNA. Examples of extranuclear DNAs are mitochondrial DNA (mtDNA) and chloroplast DNA (cpDNA). The presence of nucleic acids in these organelles enables them to become semi-autonomous, self-reproducing organelles. These organelles have their own genetic system that enables DNA replication and protein synthesis although certain proteins for replication and protein synthesis are still encoded by the nuclear DNA. Apart from replication and protein synthesis, mtDNA and cpDNA code for proteins crucial to their functions. For instance, genes in the mitochondrial genome encode for proteins in the electron transport chain. Genes in the chloroplast genome encodes for proteins used in photosynthesis. Contrary to the nuclear DNA, both cpDNA and mtDNA occur in multiple copies since there are several chloroplasts and mitochondria while there is usually just one nucleus inside a cell. A cell would therefore contain several copies of mtDNA and cpDNA, often in thousands. Nuclear DNAs are compacted into chromatin structures through histones whereas mtDNA and cpDNA are not. Many scientists believe that mtDNA and cpDNA are genetic material that came from ancient endosymbionts. Endosymbiotic theory suggests that mitochondria and chloroplasts came about as a result of the early endosymbiosis between prokaryotic endosymbionts and eukaryotic host cell. The basis is the genetic material contained in these organelles that resemble prokaryotic DNAs, i.e. being circular and lacking in histones.


The extranuclear DNA apparently does not follow the Mendelian pattern of inheritance. mtDNA and cpDNA are believed to be maternally-inherited. In humans, mtDNA is used in forensics and genealogy to trace the ancestral female line of an individual. This is based on the notion that at fertilization the head of the sperm cell fuses with the egg cell so that their nuclear DNA could form a union. As for the mtDNA, the only source would be the ovum since the sperm's mitochondrial genome would end up disintegrating together with its flagellum and other cytoplasmic structures during fertilization.


Common biological reactions

DNA replication

DNA replication is a process whereby the original (parent) strands of DNA in the double helix are separated and each one is copied to produce a new (daughter) strand. This process is said to be semi-conservative since one of each parent strand is conserved and remains intact after replication has taken place. Several enzymes, e.g. DNA polymerases, are involved in DNA replication. One of the parental strands of the DNA molecule is replicated by base pairing so that the newly synthesized strand would be complementary to the original or parent strand. That is the purine nucleobase (i.e. adenine and guanine) is paired with the pyrimidine nucleobase (i.e. cytosine and thymine). In particular, the adenine will be paired with thymine while guanine with cytosine. DNA replication is necessary in cell division. In the early stages of mitosis (prophase) and meiosis (prophase I), DNA is replicated in preparation for the late stages where the cell divides to give rise to two cells containing identical copies of DNA. After replication, copies of DNA molecule are checked by proofreading mechanisms. DNA replication can be carried out artificially through a laboratory technique called polymerase chain reaction that can amplify the target DNA fragment from the genome.


Transcription

DNA carries the genetic information that codes for a particular protein. Thus, during protein translation, the genetic code for a protein is first copied into the RNA (specifically, mRNA). This process of creating a copy of DNA into mRNA through the help of the enzyme RNA polymerase is called transcription. Although RNA polymerase traverses the DNA template strand from 3' → 5', the coding (non-template) strand is usually used as the reference point. Hence, the process proceeds in the 5' → 3' direction, like in DNA replication. However, unlike DNA replication, transcription does not need a primer to start and it uses base pairing to create an RNA copy containing uracil instead of thymine. In prokaryotes transcription occurs in the cytoplasm whereas in eukaryotes it takes place primarily in the nucleus before the mRNAis transported into the cytoplasm for translation or for protein synthesis.


Degradation

The degradation of nucleic acids like DNA yields purines, pyrimidines, phosphoric acid, and a pentose, either D-ribose or D-deoxyribose.


Repair

Certain mutations or errors occurring in the DNA are repaired by two major mechanisms: (1) the direct reversal of the chemical process that caused the damage and (2) the replacement of damaged nitrogenous bases. In direct reversal DNA repair mechanism, a template is not required and the change is superseded as the original nucleotide is restored. In DNA repair by excision, a template is required. Repair is carried out by excising and replacing the damaged DNA with new nucleotides. The excision repair is of three forms: (1) base-excision repair (where a single nucleotide change is recognized and subsequently excised by glycosylases), (2) nucleotide excision repair (where multiple base changes are recognized and then cleaved by endonucleases), and (3) mismatch repair (when mismatched bases are later recognized and eventually corrected by excising the error).[4]


Biological importance

DNA contains the genetic information of many organisms. This biomolecule is regarded as the most crucial biomolecule for its involvement in all cellular functions and heredity. DNA mutation is a vital source of variability among species. Although not all mutations could lead to significant changes in the expression of the genetic code, some of these mutations could lead to the improvement of a species, enabling an organism to acquire novel characteristics that could help it adapt better or survive in its environment. However, there are also certain mutations in the genetic code that are pathological, meaning they could lead to impaired protein function and eventuate to metabolic disorders and physical deformities. Many of such disorders are due to a supposedly functional protein that apparently became insufficiently produced or has become dysfunctional due to a mutation in the gene(s) coding for it.


DNA that comprises the genome of an organism could be passed on to the succeeding generations, either in part (via sexual reproduction) or as a whole (as in the case of parthenogenesis, cloning, or other asexual mode of reproduction). Thus, apart from inheriting beneficial features, the offspring might also inherit certain disorders and diseases from its parents.



Supplementary

Abbreviation(s)

  • DNA

Variant(s)

  • desoxyribonucleic acid

Synonym(s)

  • deoxyribose nucleic acid
  • desoxyribose nucleic acid

Derived term(s)


Further reading

Compare

See also



Reference

  1. "nucleic acid". (2014). Retrieved from [Link]
  2. Gribbin, J. (2002). The Scientists: A History of Science Told Through the Lives of Its Greatest Inventors. New York: Random House. p. 546. ISBN 0812967887.
  3. The Nobel Prize in Physiology or Medicine 1968. (2019). Retrieved from [Link]
  4. Gonzaga, M. V. (2018, July 22). How cell fixes DNA damage - Biology Blog & Dictionary Online. (2018, July 22). Retrieved from [Link]




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