Functional divergence

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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.[1][2]

Functional divergence is just one possible outcome of gene duplication events. Other fates include nonfunctionalization where one of the paralogs acquires deleterious mutations and becomes a pseudogene and superfunctionalization (reinforcement),[3] where both paralogs maintain original function. While gene, chromosome, or whole genome duplication events are considered the canonical sources of functional divergence of paralogs, orthologs (genes descended from speciation events) can also undergo functional divergence [4][5][6][7] and horizontal gene transfer can also result in multiple copies of a gene in a genome, providing the opportunity for functional divergence.

Many well known protein families are the result of this process, such as the ancient gene duplication event that led to the divergence of hemoglobin and myoglobin, the more recent duplication events that led to the various subunit expansions (alpha and beta) of vertebrate hemoglobins,[8] or the expansion of G-protein alpha subunits [9]

See also[edit]


  1. ^ Gu, X (Jul 2003). "Functional divergence in protein (family) sequence evolution". Genetica. 118 (2–3): 133–41. doi:10.1007/978-94-010-0229-5_4.
  2. ^ Fay, JC; Wu, CI (2003). "Sequence divergence, functional constraint, and selection in protein evolution". Annu Rev Genom Hum Genet. 4: 213–35.
  3. ^ Dvornyk, V; Vinogradova, ON; Nevo, E (2002). "Long-term microclimatic stress causes rapid adaptive radiation of kaiABC clock gene family in a cyanobacterium, Nostoc linckia, from "Evolution Canyons" I and II, Israel". Proc Natl Acad Sci USA. 99 (4): 2082–2087. Bibcode:2002PNAS...99.2082D. doi:10.1073/pnas.261699498. PMC 123721. PMID 11842226.
  4. ^ Studer, RA; Robinson-Rechavi, M (2009). "How confident can we be that orthologs are similar, but paralogs differ?". Trends in Genetics. 25: 210–6. doi:10.1016/j.tig.2009.03.004. PMID 19368988.
  5. ^ Studer; Robinson-Rechavi, M (2010). "Large-scale analysis of orthologs and paralogs under covarion-like and constant-but-different models of amino acid evolution". Molecular Biology and Evolution. 27: 2618–2627. doi:10.1093/molbev/msq149. PMC 2955734. PMID 20551039.
  6. ^ Gharib, WH; Robinson-Rechavi, M (2011). "When orthologs diverge between human and mouse". Briefings in Bioinformatics. 12: 436–441. doi:10.1093/bib/bbr031.
  7. ^ Nehrt, NL; Clark, WT; Radivojac, P; Hahn, MW (2011). "Testing the ortholog conjecture with comparative functional genomic data from mammals". PLOS Computational Biology. 7: e1002073. Bibcode:2011PLSCB...7E2073N. doi:10.1371/journal.pcbi.1002073. PMC 3111532. PMID 21695233.
  8. ^ Storz, Jay F.; Hoffmann, Federico G.; Opazo, Juan C.; Moriyama, Hideaki (March 2008). "Adaptive Functional Divergence Among Triplicated α-Globin Genes in Rodents". Genetics. 178 (3): 1623–1638. doi:10.1534/genetics.107.080903. PMC 2278084.
  9. ^ Zheng, Y; Xu, D; Gu, X (2007). "Functional divergence after gene duplication and sequence-structure relationship: a case study of G-protein alpha subunits". J Exp Zool B Mol Dev Evol. 308 (1): 85–96.
  • Gu, X (Oct 2006). "A simple statistical method for estimating type-II (cluster-specific) functional divergence of protein sequences". Mol Biol Evol. 23 (10): 1937–45. doi:10.1093/molbev/msl056.