In biology, a mutation is the permanent alteration of the nucleotide sequence of the genome of an organism, virus, or extrachromosomal DNA or other genetic elements. Mutations result from errors during DNA replication or other types of damage to DNA, which may undergo error-prone repair, or cause an error during other forms of repair, or else may cause an error during replication. Mutations may result from insertion or deletion of segments of DNA due to mobile genetic elements. Mutations may or may not produce discernible changes in the observable characteristics of an organism. Mutations play a part in both normal and abnormal biological processes including: evolution and the development of the immune system, including junctional diversity; the genomes of RNA viruses are based on RNA rather than DNA. The RNA viral genome can be double single stranded. In some of these viruses replication occurs and there are no mechanisms to check the genome for accuracy; this error-prone process results in mutations.
Mutation can result in many different types of change in sequences. Mutations in genes can either have no effect, alter the product of a gene, or prevent the gene from functioning properly or completely. Mutations can occur in nongenic regions. One study on genetic variations between different species of Drosophila suggests that, if a mutation changes a protein produced by a gene, the result is to be harmful, with an estimated 70 percent of amino acid polymorphisms that have damaging effects, the remainder being either neutral or marginally beneficial. Due to the damaging effects that mutations can have on genes, organisms have mechanisms such as DNA repair to prevent or correct mutations by reverting the mutated sequence back to its original state. Mutations can involve the duplication of large sections of DNA through genetic recombination; these duplications are a major source of raw material for evolving new genes, with tens to hundreds of genes duplicated in animal genomes every million years.
Most genes belong to larger gene families of shared ancestry. Novel genes are produced by several methods through the duplication and mutation of an ancestral gene, or by recombining parts of different genes to form new combinations with new functions. Here, protein domains act as modules, each with a particular and independent function, that can be mixed together to produce genes encoding new proteins with novel properties. For example, the human eye uses four genes to make structures that sense light: three for cone cell or color vision and one for rod cell or night vision. Another advantage of duplicating a gene is. Other types of mutation create new genes from noncoding DNA. Changes in chromosome number may involve larger mutations, where segments of the DNA within chromosomes break and rearrange. For example, in the Homininae, two chromosomes fused to produce human chromosome 2. In evolution, the most important role of such chromosomal rearrangements may be to accelerate the divergence of a population into new species by making populations less to interbreed, thereby preserving genetic differences between these populations.
Sequences of DNA that can move about the genome, such as transposons, make up a major fraction of the genetic material of plants and animals, may have been important in the evolution of genomes. For example, more than a million copies of the Alu sequence are present in the human genome, these sequences have now been recruited to perform functions such as regulating gene expression. Another effect of these mobile DNA sequences is that when they move within a genome, they can mutate or delete existing genes and thereby produce genetic diversity. Nonlethal mutations increase the amount of genetic variation; the abundance of some genetic changes within the gene pool can be reduced by natural selection, while other "more favorable" mutations may accumulate and result in adaptive changes. For example, a butterfly may produce offspring with new mutations; the majority of these mutations will have no effect. If this color change is advantageous, the chances of this butterfly's surviving and producing its own offspring are a little better, over time the number of butterflies with this mutation may form a larger percentage of the population.
Neutral mutations are defined as mutations whose effects do not influence the fitness of an individual. These can increase in frequency over time due to genetic drift, it is believed that the overwhelming majority of mutations have no significant effect on an organism's fitness. DNA repair mechanisms are able to mend most changes before they become permanent mutations, many organisms have mechanisms for eliminating otherwise-permanently mutated somatic cells. Beneficial mutations can improve reproductive success. Mutationism is one of several alternatives to evolution by natural selection that have existed both before and after the publication of Charles Darwin's 1859 book, On the Origin of Species. In the theory, mutation was the source of novelty
Genomics is an interdisciplinary field of biology focusing on the structure, evolution and editing of genomes. A genome is an organism's complete set including all of its genes. In contrast to genetics, which refers to the study of individual genes and their roles in inheritance, genomics aims at the collective characterization and quantification of genes, which direct the production of proteins with the assistance of enzymes and messenger molecules. In turn, proteins make up body structures such as organs and tissues as well as control chemical reactions and carry signals between cells. Genomics involves the sequencing and analysis of genomes through uses of high throughput DNA sequencing and bioinformatics to assemble and analyze the function and structure of entire genomes. Advances in genomics have triggered a revolution in discovery-based research and systems biology to facilitate understanding of the most complex biological systems such as the brain; the field includes studies of intragenomic phenomena such as epistasis, pleiotropy and other interactions between loci and alleles within the genome.
From the Greek ΓΕΝ gen, "gene" meaning "become, creation, birth", subsequent variants: genealogy, genetics, genomere, genus etc. While the word genome was in use in English as early as 1926, the term genomics was coined by Tom Roderick, a geneticist at the Jackson Laboratory, over beer at a meeting held in Maryland on the mapping of the human genome in 1986. Following Rosalind Franklin's confirmation of the helical structure of DNA, James D. Watson and Francis Crick's publication of the structure of DNA in 1953 and Fred Sanger's publication of the Amino acid sequence of insulin in 1955, nucleic acid sequencing became a major target of early molecular biologists. In 1964, Robert W. Holley and colleagues published the first nucleic acid sequence determined, the ribonucleotide sequence of alanine transfer RNA. Extending this work, Marshall Nirenberg and Philip Leder revealed the triplet nature of the genetic code and were able to determine the sequences of 54 out of 64 codons in their experiments.
In 1972, Walter Fiers and his team at the Laboratory of Molecular Biology of the University of Ghent were the first to determine the sequence of a gene: the gene for Bacteriophage MS2 coat protein. Fiers' group expanded on their MS2 coat protein work, determining the complete nucleotide-sequence of bacteriophage MS2-RNA and Simian virus 40 in 1976 and 1978, respectively. In addition to his seminal work on the amino acid sequence of insulin, Frederick Sanger and his colleagues played a key role in the development of DNA sequencing techniques that enabled the establishment of comprehensive genome sequencing projects. In 1975, he and Alan Coulson published a sequencing procedure using DNA polymerase with radiolabelled nucleotides that he called the Plus and Minus technique; this involved two related methods that generated short oligonucleotides with defined 3' termini. These could be fractionated by electrophoresis on a polyacrylamide gel and visualised using autoradiography; the procedure could sequence up to 80 nucleotides in one go and was a big improvement, but was still laborious.
In 1977 his group was able to sequence most of the 5,386 nucleotides of the single-stranded bacteriophage φX174, completing the first sequenced DNA-based genome. The refinement of the Plus and Minus method resulted in the chain-termination, or Sanger method, which formed the basis of the techniques of DNA sequencing, genome mapping, data storage, bioinformatic analysis most used in the following quarter-century of research. In the same year Walter Gilbert and Allan Maxam of Harvard University independently developed the Maxam-Gilbert method of DNA sequencing, involving the preferential cleavage of DNA at known bases, a less efficient method. For their groundbreaking work in the sequencing of nucleic acids and Sanger shared half the 1980 Nobel Prize in chemistry with Paul Berg; the advent of these technologies resulted in a rapid intensification in the scope and speed of completion of genome sequencing projects. The first complete genome sequence of a eukaryotic organelle, the human mitochondrion, was reported in 1981, the first chloroplast genomes followed in 1986.
In 1992, the first eukaryotic chromosome, chromosome III of brewer's yeast Saccharomyces cerevisiae was sequenced. The first free-living organism to be sequenced was that of Haemophilus influenzae in 1995; the following year a consortium of researchers from laboratories across North America and Japan announced the completion of the first complete genome sequence of a eukaryote, S. cerevisiae, since genomes have continued being sequenced at an exponentially growing pace. As of October 2011, the complete sequences are available for: 2,719 viruses, 1,115 archaea and bacteria, 36 eukaryotes, of which about half are fungi. Most of the microorganisms whose genomes have been sequenced are problematic pathogens, such as Haemophilus influenzae, which has resulted in a pronounced bias in their phylogenetic distribution compared to the breadth of microbial diversity. Of the other sequenced species, most were chosen because they were well-studied model organisms or promised to become good models. Yeast (Saccharomyces
Hox genes, a subset of homeobox genes, are a group of related genes that specify regions of the body plan of an embryo along the head-tail axis of animals. Hox proteins encode and specify the characteristics of'position', ensuring that the correct structures form in the correct places of the body. For example, Hox genes in insects specify which appendages form on a segment, Hox genes in vertebrates specify the types and shape of vertebrae that will form. In segmented animals, Hox proteins thus confer segmental or positional identity, but do not form the actual segments themselves. An analogy for the Hox genes can be made to the role of a play director that calls which scene the actors should carry out next. If the play director calls the scenes in the wrong order, the overall play will be presented in the wrong order. Mutations in the Hox genes can result in body parts and limbs in the wrong place along the body. Like a play director, the Hox genes do not act in the play or participate in limb formation themselves.
The protein product of each Hox gene is a transcription factor. Each Hox gene contains a well-conserved DNA sequence known as the homeobox, of which the term "Hox" was a contraction. However, in current usage the term Hox is no longer equivalent to homeobox, because Hox genes are not the only genes to possess a homeobox sequence: humans have over 200 homeobox genes of which 39 are Hox genes. Hox genes are thus a subset of the homeobox transcription factor genes. In many animals, the organization of the Hox genes in the chromosome is the same as the order of their expression along the anterior-posterior axis of the developing animal, are thus said to display colinearity; the products of Hox genes are Hox proteins. Hox proteins are a subset of transcription factors, which are proteins that are capable of binding to specific nucleotide sequences on DNA called enhancers through which they either activate or repress hundreds of other genes; the same Hox protein can act as a repressor at an activator at another.
The ability of Hox proteins to bind DNA is conferred by a part of the protein referred to as the homeodomain. The homeodomain is a 60-amino-acid-long DNA-binding domain; this amino acid sequence folds into a "helix-turn-helix" motif, stabilized by a third helix. The consensus polypeptide chain is:. Hox proteins act in partnership with co-factors, such as PBC and Meis proteins encoded by different types of homeobox gene. Helix 1 Helix 2 Helix 3/4 ______________ __________ _________________ RRRKRTAYTRYQLLELEKEFLFNRYLTRRRRIELAHSLNLTERHIKIWFQNRRMKWKKEN....|....|....|....|....|....|....|....|....|....|....|....| 10 20 30 40 50 60 Homeobox genes, thus the homeodomain protein motif, are found in most eukaryotes. Hox genes, being a subset of homeobox genes, arose more in evolution within the animal kingdom or Metazoa. Within the animal kingdom, Hox genes are present across the bilateria, have been found in Cnidaria such as sea anemones; this implies. In bilateria, Hox genes are arranged in gene clusters, although there are many exceptions where the genes have been separated by chromosomal rearrangements.
Comparing homeodomain sequences between Hox proteins reveals greater similarity between species than within a species. In most bilaterian animals, Hox genes are expressed in staggered domains along the head-to-tail axis of the embryo, suggesting that their role in specifying position is a shared, ancient feature; the functional conservation of Hox proteins can be demonstrated by the fact that a fly can function to a large degree with a chicken Hox protein in place of its own. So, despite having a last common ancestor that lived over 550 million years ago, the chicken and fly version of the same Hox gene are similar enough to target the same downstream genes in flies. Drosophila melanogaster is an important model for understanding evolution; the general principles of Hox gene function and logic elucidated in flies will apply to all bilaterian organisms, including humans. Drosophila, like all insects, has eight Hox genes; these are clustered into two complexes, both of which are located on chromosome 3.
The Antennapedia complex consists of five genes: labial, deformed, sex combs reduced, Antennapedia. The Bithorax complex, named after the Ultrabithorax gene, consists of the remaining three genes: Ultrabithorax, abdominal-A and abdominal-B; the lab gene is the most anteriorly expressed gene. It is expressed in the head in the intercalary segment, in the midgut. Loss of function of lab results in the failure of the Drosophila embryo to internalize the mouth and head structures that develop on the outside of its body. Failure of head involution deletes the salivary glands and pharynx; the lab gene was so named because it disrupted the labial appendage.
Yeasts are eukaryotic single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, 1,500 species are identified, they are estimated to constitute 1% of all described fungal species. Yeasts are unicellular organisms which evolved from multicellular ancestors, with some species having the ability to develop multicellular characteristics by forming strings of connected budding cells known as pseudohyphae or false hyphae. Yeast sizes vary depending on species and environment measuring 3–4 µm in diameter, although some yeasts can grow to 40 µm in size. Most yeasts reproduce asexually by mitosis, many do so by the asymmetric division process known as budding. Yeasts, with their single-celled growth habit, can be contrasted with molds. Fungal species that can take both forms are called dimorphic fungi. By fermentation, the yeast species Saccharomyces cerevisiae converts carbohydrates to carbon dioxide and alcohols – for thousands of years the carbon dioxide has been used in baking and the alcohol in alcoholic beverages.
It is a centrally important model organism in modern cell biology research, is one of the most researched eukaryotic microorganisms. Researchers have used it to gather information about the biology of the eukaryotic cell and human biology. Other species of yeasts, such as Candida albicans, are opportunistic pathogens and can cause infections in humans. Yeasts have been used to generate electricity in microbial fuel cells, produce ethanol for the biofuel industry. Yeasts do not form a single phylogenetic grouping; the term "yeast" is taken as a synonym for Saccharomyces cerevisiae, but the phylogenetic diversity of yeasts is shown by their placement in two separate phyla: the Ascomycota and the Basidiomycota. The budding yeasts are classified within the phylum Ascomycota; the word "yeast" comes from Old English gist and from the Indo-European root yes-, meaning "boil", "foam", or "bubble". Yeast microbes are one of the earliest domesticated organisms. Archaeologists digging in Egyptian ruins found early grinding stones and baking chambers for yeast-raised bread, as well as drawings of 4,000-year-old bakeries and breweries.
In 1680, Dutch naturalist Anton van Leeuwenhoek first microscopically observed yeast, but at the time did not consider them to be living organisms, but rather globular structures as researchers were doubtful whether yeasts were algae or fungi. Theodor Schwann recognized them as fungi in 1837. In 1857, French microbiologist Louis Pasteur showed that by bubbling oxygen into the yeast broth, cell growth could be increased, but fermentation was inhibited – an observation called the "Pasteur effect". In the paper "Mémoire sur la fermentation alcoolique," Pasteur proved that alcoholic fermentation was conducted by living yeasts and not by a chemical catalyst. By the late 18th century two yeast strains used in brewing had been identified: Saccharomyces cerevisiae and S. carlsbergensis. S. cerevisiae has been sold commercially by the Dutch for bread-making since 1780. In 1825, a method was developed to remove the liquid; the industrial production of yeast blocks was enhanced by the introduction of the filter press in 1867.
In 1872, Baron Max de Springer developed a manufacturing process to create granulated yeast, a technique, used until the first World War. In the United States occurring airborne yeasts were used exclusively until commercial yeast was marketed at the Centennial Exposition in 1876 in Philadelphia, where Charles L. Fleischmann exhibited the product and a process to use it, as well as serving the resultant baked bread; the mechanical refrigerator liberated brewers and winemakers from seasonal constraints for the first time and allowed them to exit cellars and other earthen environments. For John Molson, who made his livelihood in Montreal prior to the development of the fridge, the brewing season lasted from September through to May; the same seasonal restrictions governed the distiller's art. Yeasts are chemoorganotrophs, as they use organic compounds as a source of energy and do not require sunlight to grow. Carbon is obtained from hexose sugars, such as glucose and fructose, or disaccharides such as sucrose and maltose.
Some species can metabolize pentose sugars such as ribose and organic acids. Yeast species either require oxygen for aerobic cellular respiration or are anaerobic, but have aerobic methods of energy production. Unlike bacteria, no known yeast species grow only anaerobically. Most yeasts grow best in a neutral or acidic pH environment. Yeasts vary in regard to the temperature range. For example, Leucosporidium frigidum grows at −2 to 20 °C, Saccharomyces telluris at 5 to 35 °C, Candida slooffi at 28 to 45 °C; the cells can survive freezing with viability decreasing over time. In general, yeasts are grown in liquid broths. Common media used for the cultivation of yeasts include potato dextrose agar or potato dextrose broth, Wallerstein Laboratories nutrient agar, yeast peptone dextrose agar, yeast mould agar or broth. Home brewers who cultivate yeast use dried malt extract and agar as a solid grow
Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes that are passed on from parent to offspring during reproduction. Different characteristics tend to exist within any given population as a result of mutation, genetic recombination and other sources of genetic variation. Evolution occurs when evolutionary processes such as natural selection and genetic drift act on this variation, resulting in certain characteristics becoming more common or rare within a population, it is this process of evolution that has given rise to biodiversity at every level of biological organisation, including the levels of species, individual organisms and molecules. The scientific theory of evolution by natural selection was proposed by Charles Darwin and Alfred Russel Wallace in the mid-19th century and was set out in detail in Darwin's book On the Origin of Species. Evolution by natural selection was first demonstrated by the observation that more offspring are produced than can survive.
This is followed by three observable facts about living organisms: 1) traits vary among individuals with respect to their morphology and behaviour, 2) different traits confer different rates of survival and reproduction and 3) traits can be passed from generation to generation. Thus, in successive generations members of a population are more to be replaced by the progenies of parents with favourable characteristics that have enabled them to survive and reproduce in their respective environments. In the early 20th century, other competing ideas of evolution such as mutationism and orthogenesis were refuted as the modern synthesis reconciled Darwinian evolution with classical genetics, which established adaptive evolution as being caused by natural selection acting on Mendelian genetic variation. All life on Earth shares a last universal common ancestor that lived 3.5–3.8 billion years ago. The fossil record includes a progression from early biogenic graphite, to microbial mat fossils, to fossilised multicellular organisms.
Existing patterns of biodiversity have been shaped by repeated formations of new species, changes within species and loss of species throughout the evolutionary history of life on Earth. Morphological and biochemical traits are more similar among species that share a more recent common ancestor, can be used to reconstruct phylogenetic trees. Evolutionary biologists have continued to study various aspects of evolution by forming and testing hypotheses as well as constructing theories based on evidence from the field or laboratory and on data generated by the methods of mathematical and theoretical biology, their discoveries have influenced not just the development of biology but numerous other scientific and industrial fields, including agriculture and computer science. The proposal that one type of organism could descend from another type goes back to some of the first pre-Socratic Greek philosophers, such as Anaximander and Empedocles; such proposals survived into Roman times. The poet and philosopher Lucretius followed Empedocles in his masterwork De rerum natura.
In contrast to these materialistic views, Aristotelianism considered all natural things as actualisations of fixed natural possibilities, known as forms. This was part of a medieval teleological understanding of nature in which all things have an intended role to play in a divine cosmic order. Variations of this idea became the standard understanding of the Middle Ages and were integrated into Christian learning, but Aristotle did not demand that real types of organisms always correspond one-for-one with exact metaphysical forms and gave examples of how new types of living things could come to be. In the 17th century, the new method of modern science rejected the Aristotelian approach, it sought explanations of natural phenomena in terms of physical laws that were the same for all visible things and that did not require the existence of any fixed natural categories or divine cosmic order. However, this new approach was slow to take root in the biological sciences, the last bastion of the concept of fixed natural types.
John Ray applied one of the more general terms for fixed natural types, "species," to plant and animal types, but he identified each type of living thing as a species and proposed that each species could be defined by the features that perpetuated themselves generation after generation. The biological classification introduced by Carl Linnaeus in 1735 explicitly recognised the hierarchical nature of species relationships, but still viewed species as fixed according to a divine plan. Other naturalists of this time speculated on the evolutionary change of species over time according to natural laws. In 1751, Pierre Louis Maupertuis wrote of natural modifications occurring during reproduction and accumulating over many generations to produce new species. Georges-Louis Leclerc, Comte de Buffon suggested that species could degenerate into different organisms, Erasmus Darwin proposed that all warm-blooded animals could have descended from a single microorganism; the first full-fledged evolutionary scheme was Jean-Baptiste Lamarck's "transmutation" theory of 1809, which envisaged spontaneous generation continually producing simple forms of life that developed greater complexity in parallel lineages with an inherent progressive tendency, postulated that on a local level, these lineages adapted to the environment by inheriting changes caused by their use or disuse in parents.
These ideas were cond
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 basis for biological inheritance; the cell possesses the distinctive property of division. DNA is made up of a double helix of two complementary strands. During replication, these strands are separated; each strand of the original DNA molecule serves as a template for the production of its counterpart, a process referred to as semiconservative replication. As a result of semi-conservative replication, the new helix will be composed of an original DNA strand as well as a newly synthesized strand. Cellular proofreading and error-checking mechanisms ensure near perfect fidelity for DNA replication. In a cell, DNA replication begins at origins of replication, in the genome. Unwinding of DNA at the origin and synthesis of new strands, accommodated by an enzyme known as helicase, results in replication forks growing bi-directionally from the origin.
A number of proteins are associated with the replication fork to help in the initiation and continuation of DNA synthesis. Most prominently, DNA polymerase synthesizes the new strands by adding nucleotides that complement each strand. DNA replication occurs during the S-stage of interphase. DNA replication can be performed in vitro. DNA polymerases isolated from cells and artificial DNA primers can be used to start DNA synthesis at known sequences in a template DNA molecule. Polymerase chain reaction, ligase chain reaction, transcription-mediated amplification are examples. DNA exists as a double-stranded structure, with both strands coiled together to form the characteristic double-helix; each single strand of DNA is a chain of four types of nucleotides. Nucleotides in DNA contain a deoxyribose sugar, a phosphate, a nucleobase; the four types of nucleotide correspond to the four nucleobases adenine, cytosine and thymine abbreviated as A, C, G and T. Adenine and guanine are purine bases, while cytosine and thymine are pyrimidines.
These nucleotides form phosphodiester bonds, creating the phosphate-deoxyribose backbone of the DNA double helix with the nucleobases pointing inward. Nucleobases are matched between strands through hydrogen bonds to form base pairs. Adenine pairs with thymine, guanine pairs with cytosine. DNA strands have a directionality, the different ends of a single strand are called the "3′ end" and the "5′ end". By convention, if the base sequence of a single strand of DNA is given, the left end of the sequence is the 5′ end, while the right end of the sequence is the 3′ end; the strands of the double helix are anti-parallel with one being 5′ to 3′, the opposite strand 3′ to 5′. These terms refer to the carbon atom in deoxyribose to which the next phosphate in the chain attaches. Directionality has consequences in DNA synthesis, because DNA polymerase can synthesize DNA in only one direction by adding nucleotides to the 3′ end of a DNA strand; the pairing of complementary bases in DNA means that the information contained within each strand is redundant.
Phosphodiester bonds are stronger than hydrogen bonds. This allows the strands to be separated from one another; the nucleotides on a single strand can therefore be used to reconstruct nucleotides on a newly synthesized partner strand. DNA polymerases are a family of enzymes. DNA polymerases in general cannot initiate synthesis of new strands, but can only extend an existing DNA or RNA strand paired with a template strand. To begin synthesis, a short fragment of RNA, called a primer, must be created and paired with the template DNA strand. DNA polymerase adds a new strand of DNA by extending the 3′ end of an existing nucleotide chain, adding new nucleotides matched to the template strand one at a time via the creation of phosphodiester bonds; the energy for this process of DNA polymerization comes from hydrolysis of the high-energy phosphate bonds between the three phosphates attached to each unincorporated base. Free bases with their attached phosphate groups are called nucleotides; when a nucleotide is being added to a growing DNA strand, the formation of a phosphodiester bond between the proximal phosphate of the nucleotide to the growing chain is accompanied by hydrolysis of a high-energy phosphate bond with release of the two distal phosphates as a pyrophosphate.
Enzymatic hydrolysis of the resulting pyrophosphate into inorganic phosphate consumes a second high-energy phosphate bond and renders the reaction irreversible. In general, DNA polymerases are accurate, with an intrinsic error rate of less than one mistake for every 107 nucleotides added. In addition, some DNA polymerases have proofreading ability. Post-replication mismatch repair mechanisms monitor the DNA for errors, being capable of distinguishing mismatches in the newly synthesized DNA strand from the original strand sequence. Together, these three discrimination steps enable replication fidelity of less than one mistake for every 109 nucleotides added; the rate of DNA replication in a living cell was first measured as the rate of phage T4 DNA elongation in phage-infected E. coli. During the period of exponential DNA increase at 37 °C, the rate was 749 nucleotides per second
Neofunctionalization, one of the possible outcomes of functional divergence, occurs when one gene copy, or paralog, takes on a new function after a gene duplication event. Neofunctionalization is an adaptive mutation process. In other words, one of the duplicates retains its original function, while the other accumulates molecular changes such that, in time, it can perform a different task; this process is thought to be free of selective pressure because one gene copy can mutate without adversely affecting the fitness of the organism since ancestral function is retained in the other copy. The process of Neofunctionalization begins with a gene duplication event, thought to occur as a defense mechanism against the accumulation of deleterious mutations. Following the gene duplication event there are two identical copies of the ancestral gene performing the same function; this redundancy allows one. In the event that the new function is advantageous, natural selection positively selects for it and the new mutation becomes fixed in the population.
The occurrence of Neofunctionalization can most be attributed to changes in the coding region or changes in the regulatory elements of a gene. It is much more rare to see major changes in protein function, such as subunit structure or substrate and ligand affinity, as a result of Neofunctionalization. Neofunctionalization is commonly referred to as "mutation during non-functionality” or “mutation during redundancy”. Regardless of if the mutation arises after non-functionality of a gene or due to redundant gene copies, the important aspect is that in both scenarios one copy of the duplicated gene is freed from selective constraints and by chance acquires a new function, improved by natural selection; this process is thought to occur rarely in evolution for two major reasons. The first reason is that functional changes require a large number of amino acid changes. Secondly, because deleterious mutations occur much more than advantageous mutations in evolution; this makes the likelihood that gene function is lost over time far greater than the likelihood of the emergence of a new gene function.
Walsh discovered that the relative probability of Neofunctionalization is determined by the selective advantage and the relative rate of advantageous mutations. This was proven in his derivation of the relative probability of Neofunctionalization to pseudogenization, given by: ρ S − 1 1 − e s where ρ is the ratio of advantageous mutation rate to null mutation rate and S is the population selection 4NeS. In 1936, Muller proposed Neofunctionalization as a possible outcome of a gene duplication event. In 1970, Ohno suggested that Neofunctionalization was the only evolutionary mechanism that gave rise to new gene functions in a population, he believed that Neofunctionalization was the only alternative to pseudogenization. Ohta was among the first to suggest that other mechanisms may exist for the preservation of duplicated genes in the population. Today, subfunctionalization is a accepted alternative fixation process for gene duplicates in the population and is the only other possible outcome of functional divergence.
Neosubfunctionalization occurs. In other words, once a gene duplication event occurs forming parologs that after an evolutionary period subfunctionalize, one gene copy continues on this evolutionary journey and accumulates mutations that give rise to a new function; some believe. For instance, according to Rastogi and Liberles “Neofunctionalization is the terminal fate of all duplicate gene copies retained in the genome and subfuctionlization exist as a transient state to preserve the duplicate gene copy.” The results of their study become punctuated as population size increases. The evolution of the antifreeze protein in the Antarctic zoarcid fish provides a prime example of Neofunctionalization after gene duplication. In the case of the Antarctic zoarcid fish type III antifreeze protein gene diverged from a parologus copy of sialic acid synthase gene; the ancestral SAS gene was found to have both sialic acid synthase and rudimentary ice-binding functionalities. After duplication one of the paralogs began to accumulate mutations that lead to the replacement of SAS domains of the gene allowing for further development and optimization of the antifreeze functionality.
The new gene is now capable of noncolligative freezing-point depression, thus is neofunctionalized. This specialization allows Antarctic zoarcid fish to survive in the frigid temperatures of the Antarctic Seas. Limitations exist in Neofunctionalization as model for functional divergence because: the amount of nucleotide changes giving rise to a new function must be minimal. After a gene duplication event both copies may be subjected to selective pressure equivalent to that constraining the ancestral gene. In many cases positive Darwinian selection presents a more parsimonious explanation for the divergence of multigene families. Subfunctionalization