Ellegren H: Substitution rate heterogeneity and the male mutation bias

Abstract. Germline mutation rates have been found to be higher in males than in females in many organ-isms, a likely consequence of cell division being more frequent in spermatogenesis than in oogenesis. If the majority of mutations are due to DNA replication er-ror, the male-to-female mutation rate ratio (am) is ex-pected to be similar to the ratio of the number of germ line cell divisions in males and females (c), an assumption that can be tested with proper estimates of am and c. am is usually estimated by comparing sub-stitution rates in putatively neutral sequences on the sex chromosomes. However, substantial regional var-iation in substitution rates across chromosomes may bias estimates of am based on the substitution rates of short sequences. To investigate regional substitution rate variation, we estimated sequence divergence in 16 gametologous introns located on the Z and W chro-mosomes of five bird species of the order Galliformes. Intron ends and potentially conserved blocks were excluded to reduce the effect of using sequences subject to negative selection.We found significant substitution rate variation within Z chromosome (G15 = 37.6, p = 0.0010) as well as within W chromosome introns (G15 = 44.0, p = 0.0001). This heterogeneity also affected the estimates of am, which varied significantly, from 1.53 to 3.51, among the introns (ANOVA: F13,14 =2.68, p = 0.04). Our results suggest the importance of using extensive data sets from several genomic re-gions to avoid the effects of regional mutation rate variation and to ensure accurate estimates of am. Key words: Male mutation bias — Sex chromo-somes — Birds — Substitution rate variatio