Neofunctionalization

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Neofunctionalization is the process by which a gene acquires a new function after a gene duplication event. The figure shows that once a gene duplication event has occurred one gene copy retains the original ancestral function (represented by the green paralog), while the other acquires mutations that allow it to diverge and develop a new function (represented by the blue paralog). Neofunctionalization after a gene duplication event.png
Neofunctionalization is the process by which a gene acquires a new function after a gene duplication event. The figure shows that once a gene duplication event has occurred one gene copy retains the original ancestral function (represented by the green paralog), while the other acquires mutations that allow it to diverge and develop a new function (represented by the blue paralog).

Neofunctionalization, one of the possible outcomes of functional divergence, occurs when one gene copy, or paralog, takes on a totally new function after a gene duplication event. Neofunctionalization is an adaptive mutation process; meaning one of the gene copies must mutate to develop a function that was not present in the ancestral gene. [1] [2] [3] 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. [4]

Contents

The process

The process of neofunctionalization begins with a gene duplication event, which is thought to occur as a defense mechanism against the accumulation of deleterious mutations. [5] [6] [7] Following the gene duplication event there are two identical copies of the ancestral gene performing exactly the same function. This redundancy allows one the copies to take on a new function. In the event that the new function is advantageous, natural selection positively selects for it and the new mutation becomes fixed in the population. [3] [8] The occurrence of neofunctionalization can most often be attributed to changes in the coding region or changes in the regulatory elements of a gene. [6] 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. [6]

Selective constraints

Neofunctionalization is also commonly referred to as "mutation during non-functionality" or "mutation during redundancy". [9] 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 which is then improved by natural selection. [6] This process is thought to occur very rarely in evolution for two major reasons. The first reason is that functional changes typically require a large number of amino acid changes; which has a low probability of occurrence. Secondly, because deleterious mutations occur much more frequently than advantageous mutations in evolution. [6] This makes the likelihood that gene function is lost over time (i.e. pseudogenization) far greater than the likelihood of the emergence of a new gene function. [8] Walsh discovered that the relative probability of neofunctionalization is determined by the selective advantage and the relative rate of advantageous mutations. [10] This was proven in his derivation of the relative probability of neofunctionalization to pseudogenization, which is given by: where ρ is the ratio of advantageous mutation rate to null mutation rate and S is the population selection 4NeS (Ne: effective population size S: selection intensity). [10]

Classical model

In 1936, Muller originally proposed neofunctionalization as a possible outcome of a gene duplication event. [11] In 1970, Ohno suggested that neofunctionalization was the only evolutionary mechanism that gave rise to new gene functions in a population. [6] He also believed that neofunctionalization was the only alternative to pseudogenization. [2] Ohta (1987) was among the first to suggest that other mechanisms may exist for the preservation of duplicated genes in the population. [6] Today, subfunctionalization is a widely accepted alternative fixation process for gene duplicates in the population and is currently the only other possible outcome of functional divergence. [2]

Neosubfunctionalization

Neosubfunctionalization occurs when neofunctionalization is the end result of subfunctionalization. In other words, once a gene duplication event occurs forming paralogs that after an evolutionary period subfunctionalize, one gene copy continues on this evolutionary journey and accumulates mutations that give rise to a new function. [6] [12] Some believe that neofunctionalization is the end stage for all subfunctionalized genes. For instance, according to Rastogi and Liberles "Neofunctionalization is the terminal fate of all duplicate gene copies retained in the genome and subfunctionlization merely exist as a transient state to preserve the duplicate gene copy." [2] The results of their study become punctuated as population size increases.

Examples

The evolution of the antifreeze protein in the Antarctic zoarcid fish Lycodichthys dearborni provides a prime example of neofunctionalization after gene duplication. In the case of the Antarctic zoarcid fish type III antifreeze protein gene (AFPIII; P12102 ) diverged from a paralogous copy of sialic acid synthase (SAS) gene. [13] 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. [13] The new gene is now capable of noncolligative freezing-point depression, and thus is neofunctionalized. [13] This specialization allows Antarctic zoarcid fish to survive in the frigid temperatures of the Antarctic Seas.

Another example concerns the light-sensitive opsin proteins in vertebrate eyes that allow them to see different wavelengths of light. Extant vertebrates typically have four cone opsin classes (LWS, SWS1, SWS2, and Rh2) as well as one rod opsin class (rhodopsin, Rh1), all of which were inherited from early vertebrate ancestors. These five classes of vertebrate visual opsins emerged through a series of gene duplications beginning with LWS and ending with Rh1. [14] [15]

Model limitations

Limitations exist in neofunctionalization as a model for functional divergence primarily because:

  1. the amount of nucleotide changes giving rise to a new function must be very minimal; making the probability for pseudogenization much higher than neofunctionalization after a gene duplication event. [6]
  2. After a gene duplication event both copies may be subjected to selective pressure equivalent to that constraining the ancestral gene; meaning that neither copy is available for neofunctionalization. [6]
  3. In many cases positive Darwinian selection presents a more parsimonious explanation for the divergence of multigene families. [6]

See also

Related Research Articles

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Molecular evolution describes how inherited DNA and/or RNA change over evolutionary time, and the consequences of this for proteins and other components of cells and organisms. Molecular evolution is the basis of phylogenetic approaches to describing the tree of life. Molecular evolution overlaps with population genetics, especially on shorter timescales. Topics in molecular evolution include the origins of new genes, the genetic nature of complex traits, the genetic basis of adaptation and speciation, the evolution of development, and patterns and processes underlying genomic changes during evolution.

<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.

Gene duplication 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.

<span class="mw-page-title-main">Gene family</span> Set of several similar genes

A gene family is a set of several similar genes, formed by duplication of a single original gene, and generally with similar biochemical functions. One such family are the genes for human hemoglobin subunits; the ten genes are in two clusters on different chromosomes, called the α-globin and β-globin loci. These two gene clusters are thought to have arisen as a result of a precursor gene being duplicated approximately 500 million years ago.

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

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

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Functional divergence is the process by which genes, after gene duplication, shift in function from an ancestral function. Functional divergence can result in either subfunctionalization, where a paralog specializes one of several ancestral functions, or neofunctionalization, where a totally new functional capability evolves. It is thought that this process of gene duplication and functional divergence is a major originator of molecular novelty and has produced the many large protein families that exist today.

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

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References

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  12. ↑ He X, Zhang J (February 2005). "Rapid subfunctionalization accompanied by prolonged and substantial neofunctionalization in duplicate gene evolution". Genetics. 169 (2): 1157–64. doi:10.1534/genetics.104.037051. PMC   1449125 . PMID   15654095.
  13. 1 2 3 Deng C, Cheng CH, Ye H, He X, Chen L (December 2010). "Evolution of an antifreeze protein by neofunctionalization under escape from adaptive conflict". Proceedings of the National Academy of Sciences of the United States of America. 107 (50): 21593–8. Bibcode:2010PNAS..10721593D. doi: 10.1073/pnas.1007883107 . PMC   3003108 . PMID   21115821.
  14. ↑ Hunt DM, Carvalho LS, Cowing JA, Davies WL (October 2009). "Evolution and spectral tuning of visual pigments in birds and mammals". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 364 (1531): 2941–2955. doi:10.1098/rstb.2009.0044. PMC   2781856 . PMID   19720655.
  15. ↑ Trezise AE, Collin SP (October 2005). "Opsins: evolution in waiting". Current Biology. 15 (19): R794–R796. Bibcode:2005CBio...15.R794T. doi: 10.1016/j.cub.2005.09.025 . PMID   16213808.
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