The probability of duplicate gene preservation by subfunctionalization

Michael Lynch, Allan Force

Research output: Contribution to journalArticlepeer-review

1210 Scopus citations


It has often been argued that gene-duplication events are most commonly followed by a mutational event that silences one member of the pair, while on rare occasions both members of the pair are preserved as one acquires a mutation with a beneficial function and the other retains the original function. However, empirical evidence from genome duplication events suggests that gene duplicates are preserved in genomes far more commonly and for periods far in excess of the expectations under this model, and whereas some gene duplicates clearly evolve new functions, there is little evidence that this is the most common mechanism of duplicate-gene preservation. An alternative hypothesis is that gene duplicates are frequently preserved by subfunctionalization, whereby both members of a pair experience degenerative mutations that reduce their joint levels and patterns of activity to that of the single ancestral gene. We consider the ways in which the probability of duplicate-gene preservation by such complementary mutations is modified by aspects of gene structure, degree of linkage, mutation rates and effects, and population size. Even if most mutations cause complete loss-of-subfunction, the probability of duplicate-gene preservation can be appreciable if the long-term effective population size is on the order of 105 or smaller, especially if there are more than two independently mutable subfunctions per locus. Even a moderate incidence of partial loss-of-function mutations greatly elevates the probability of preservation. The model proposed herein leads to quantitative predictions that are consistent with observations on the frequency of long-term duplicate gene preservation and with observations that indicate that a common fate of the members of duplicate-gene pairs is the partitioning of tissue-specific patterns of expression of the ancestral gene.

Original languageEnglish (US)
Pages (from-to)459-473
Number of pages15
Issue number1
StatePublished - Jan 2000
Externally publishedYes

ASJC Scopus subject areas

  • Genetics


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