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Substitution Rate Heterogeneity and the Male Mutation Bias

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Abstract

Germline mutation rates have been found to be higher in males than in females in many organisms, a likely consequence of cell division being more frequent in spermatogenesis than in oogenesis. If the majority of mutations are due to DNA replication error, the male-to-female mutation rate ratio (αm) is expected 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 αm and c. αm is usually estimated by comparing substitution rates in putatively neutral sequences on the sex chromosomes. However, substantial regional variation in substitution rates across chromosomes may bias estimates of αm 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 chromosomes 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 αm, 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 regions to avoid the effects of regional mutation rate variation and to ensure accurate estimates of αm.

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Acknowledgments

Financial support was obtained from the Swedish Research Council to H.E and to S.B. H.E. is a Royal Academy of Sciences Research Fellow supported by a grant from the Knut and Alice Wallenberg Foundation. Cecilia Berg, Jacob Höglund, Anna Mattsson, and Ettore Randi are acknowledged for help with DNA samples.

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  1. Sofia Berlin

    Present address: Department of Genetics and Genomics, Roslin Institute (Edinburgh), Roslin, Midlothian, EH25 9PS, UK

Authors and Affiliations

  1. Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Norbyvägen 18 D, Uppsala, SE-752 36, Sweden

    Sofia Berlin, Mikael Brandström, Niclas Backström, Erik Axelsson, Nick G.C. Smith & Hans Ellegren

  2. Department of Mathematics and Statistics, Lancaster University, Lancaster, LA1 4YF, UK

    Nick G.C. Smith

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  1. Sofia Berlin
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Correspondence to Hans Ellegren.

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[Reviewing Editor: Mr. Martin Kreitman]

Nick G.C. Smith Deceased

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Berlin, S., Brandström, M., Backström, N. et al. Substitution Rate Heterogeneity and the Male Mutation Bias. J Mol Evol 62, 226–233 (2006). https://doi.org/10.1007/s00239-005-0103-6

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  • DOI: https://doi.org/10.1007/s00239-005-0103-6

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