THE EVOLUTION OF CONCERTED EVOLUTION

Concerted evolution is a consequence of processes that convert copies of a gene in a multigene family into the same copy. Here we ask whethe r this homogenization may be adaptive. Analysis of a modifier of homog enization reveals (1) that the trait is most likely to spread if inter actions between deleterious mutations are not strongly synergistic; (2 ) that selection on the modifier is of the order of the mutation rate, hence the modifier is most likely to be favoured by selection when th e species has a large effective population size and/or if the modifier affects many genes simultaneously; and (3) that linkage between the g enes in the family, and between these genes and the modifier, makes in vasion of the modifier easier, suggesting that selection may favour mu ltigene families being in clustered arrays. It follows from the first conclusion that genes for which mutations may often be dominant or sem i-dominant should undergo concerted evolution more commonly than other s. By analysis of the mouse knockout database, we show that mutations affecting growth-related genes are more commonly associated with domin ant lethality than expected by chance. We predict then that selection will favour homogenization of such genes, and possibly others that are significantly dosage dependent, more often than it favours homogeniza tion in other genes. The first condition is almost the opposite of tha t required for the maintenance of sexual reproduction according to the mutation-deterministic theory. The analysis here therefore suggests t hat sexual organisms can simultaneously minimize both the effects of d eleterious, strongly synergistically, interacting mutations and those that interact either weakly synergistically, multiplicatively, or anta gonistically, assuming the latter class belong to a multicopy gene fam ily. Recombination and an absence of homogenization are efficient in p urging deleterious mutations in the former class, homogenization and a n absence of recombination are efficient at minimizing the costs impos ed by the latter classes.