Evolution and Variation of Multigene Families.

Abstract

0.005 to 0.04 per billion years, respectively) are similar to the estimate from genes with T m 0 T 0 , which is not expected if the gene loss rate is much higher than the gene duplication rate. The data also allow us to quantify the duration of concerted evolution and the level of gene conversion. The question of the duration of concerted evolution is addressed according to the recent theoretical result of Teshima and Innan (8), who showed that the period of concerted evolution approximately follows an exponential distribution with parameter 1/t, where t is the expected length of concerted evolution. The probability (f) that the duration of concerted evolution from a certain time point (t s) exceeds another time point (t e) is given by expE-(t e-t s)/t^. To estimate t assuming a constant t for all gene pairs, we considered two time points, T 4 and T 1 , on the species tree (Fig. 1A). We focused on the 51 gene pairs for which concerted evolution was likely occurring at T 4. For each of these 51 gene pairs, we considered whether concerted evolution was still going on at T 1 by comparing Ks among four gene sequences, two from S. cerevisiae and two from S. paradoxus. We found smaller values of Ks between the paralogs within species than between orthologs for nine gene pairs that were considered to be under concerted evolution at T 1. We could then estimate f 0 9/51, from which an estimate of t 0 0.2 was obtained by solving exp(-0.35/t) 0 f, where 0.35 is the time between T 1 and T 4 measured in units of 1/Ks. Assuming the synonymous substitution rate Ks 0 8.1 Â 10-9 , the estimate yields t 0 25 million years (13). The rate of gene conversion is one of the important factors in determining the period of concerted evolution. The gene conversion rate can be directly estimated from the nucleotide divergence between gene pairs currently under concerted evolution. Because it was not possible to determine such gene pairs, we used the nine gene pairs that are likely under concerted evolution at T 1 as a proxy, for which the average d 0 0.036. The expectation of d is given by m/c, where m is the mutation rate per site and c is the gene conversion rate per site (17, 18); hence, we estimate that the gene conversion rate is È28 times the mutation rate, assuming that c is constant for all duplicated genes (13). This is within the range of estimates (10 to 100) in Drosophila duplicated genes (18). Our demonstration of extensive concerted evolution via gene conversion on a genome scale is consistent with molecular genetic studies showing frequent interlocus gene conversion in yeast (19). Although yeast is a model species for studying gene conversion , there is no reason to believe that the effect of gene conversion in duplicated genes is negligible in other organisms. Increasing evidence for gene conversion (interlocus as well as intralocus) is also available in higher eukaryotes, such as humans (20-23), Dro-sophila (18, 24, 25), and other species (26).