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. 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. S. Ohno, Evolution by Gene Duplication. New York, Heidelberg, Berlin: Springer-Verlag, 1970, pp. 59-87 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. R. De Smet and Y. Van de Peer, "Redundancy and rewiring of genetic networks following genome-wide duplication events.," Current Opinion in Plant Biology, pp. 1-9, Feb. 2012D. Graur and W.-H. Li, Fundamentals of Molecular Evolution, Second Ed. Sinauer Associates, Inc., 2000. 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. G. D. Amoutzias, Y. He, J. Gordon, D. Mossialos, S. G. Oliver, and Y. Van de Peer, "Posttranslational regulation impacts the fate of duplicated genes.," Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 7, pp. 2967-71, Feb. 2010 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. H. Innan, "Population genetic models of duplicated genes.," Genetica, vol. 137, no. 1, pp. 19-37, Sep. 2009 The occurrence of Neofunctionalization can most often 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 also commonly referred to as "mutation during non-functionality" or "mutation during redundancy". A. Hughes, Adaptive Evolution of Genes and Genomes. New York: Oxford University Press, 1999 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. 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. 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. 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, 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). Neosubfunctionalization Neosubfunctionalization occurs when Neofunctionalization is the end result of subfunctionalization. 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. X. He and J. Zhang, "Rapid subfunctionalization accompanied by prolonged and substantial neofunctionalization in duplicate gene evolution.," Genetics, vol. 169, no. 2, pp. 1157-1164, 2005 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 subfuctionlization merely exist as a transient state to preserve the duplicate gene copy." The results of their study become punctuated as population size increases.
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. 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 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. 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. The occurrence of Neofunctionalization can most often 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 also 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 which is then improved by natural selection. 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. 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. 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, 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). Neosubfunctionalization Neosubfunctionalization occurs when Neofunctionalization is the end result of subfunctionalization. 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 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 subfuctionlization merely exist as a transient state to preserve the duplicate gene copy." The results of their study become punctuated as population size increases.
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S. Ohno, Evolution by Gene Duplication. New York, Heidelberg, Berlin: Springer-Verlag, 1970, pp. 59-87
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R. De Smet and Y. Van de Peer, "Redundancy and rewiring of genetic networks following genome-wide duplication events.," Current Opinion in Plant Biology, pp. 1-9, Feb. 2012D. Graur and W.-H. Li, Fundamentals of Molecular Evolution, Second Ed. Sinauer Associates, Inc., 2000.
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G. D. Amoutzias, Y. He, J. Gordon, D. Mossialos, S. G. Oliver, and Y. Van de Peer, "Posttranslational regulation impacts the fate of duplicated genes.," Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 7, pp. 2967-71, Feb. 2010
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H. Innan, "Population genetic models of duplicated genes.," Genetica, vol. 137, no. 1, pp. 19-37, Sep. 2009
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A. Hughes, Adaptive Evolution of Genes and Genomes. New York: Oxford University Press, 1999
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X. He and J. Zhang, "Rapid subfunctionalization accompanied by prolonged and substantial neofunctionalization in duplicate gene evolution.," Genetics, vol. 169, no. 2, pp. 1157-1164, 2005