Very Low Rate of Gene Conversion in the Yeast Genome

Gene duplication is a major driver of organismal adaptation and evolution and plays an important role in multiple human diseases. Whole-genome analyses have shown similar and high rates of gene duplication across a variety of eukaryotic species. Most of these studies, however, did not address the possible impact of interlocus gene conversion (IGC) on the evolution of gene duplicates. Because IGC homogenizes pairs of duplicates, widespread conversion would cause gene duplication events that happened long ago to appear more recent, resulting in artificially high estimates of duplication rates. Although the majority of genome-wide studies (including in the budding yeast Saccharomyces cerevisiae [Scer]) point to levels of IGC between paralogs ranging from 2% to 18%, Gao and Innan (Gao LZ, Innan H. 2004. Very low gene duplication rate in the yeast genome. Science 306:1367-1370.) found that gene conversion in yeast affected >80% of paralog pairs. If conversion rates really are this high, it would imply that the rate of gene duplication in eukaryotes is much lower than previously reported. In this work, we apply four different methodologies-including one approach that closely mirrors Gao and Innan's method-to estimate the level of IGC in Scer. Our analyses point to a maximum conversion level of 13% between paralogs in this species, in close agreement with most estimates of IGC in eukaryotes. We also show that the exceedingly high levels of conversion found previously derive from application of an accurate method to an inappropriate data set. In conclusion, our work provides the most striking evidence to date supporting the reduced incidence of IGC among Scer paralogs and sets up a framework for future analyses in other eukaryotes.