title: Local similarity in evolutionary rates extends over whole chromosomes in human-rodent and mouse-rat comparisons: implications for understanding the mechanistic basis of the male mutation bias.
abstract: The sex chromosomes and autosomes spend different times in the germ line of the two sexes. If cell division is mutagenic and if the sexes differ in number of cell divisions, then we expect that sequences on the X and Y chromosomes and autosomes should mutate at different rates. Tests of this hypothesis for several mammalian species have led to conflicting results. At the same time, recent evidence suggests that the chromosomal location of genes on autosomes affects their rate of evolution at synonymous sites. This suggests a mutagenic source different from germ cell replication. To correctly interpret the previous estimates of male mutation bias, it is crucial to understand the degree and range of this local similarity. With a carefully chosen randomization protocol, local similarity in synonymous rates of evolution can be detected in human-rodent and mouse-rat comparisons. However, the synonymous-site similarity in the mouse-rat comparison remains weak. Simulations suggest that this difference between the mouse-human and the mouse-rat comparisons is not artifactual and that there is therefore a difference between humans and rodents in the local patterns of mutation or selection on synonymous sites (conversely, we show that the previously reported absence of a local similarity in nonsynonymous rates of evolution in the human-rodent comparison was a methodological artifact). We show that linkage effects have a long-range component: not one in a million random genomes shows such levels of autosomal heterogeneity. The heterogeneity is so great that more autosomes than expected by chance have rates of synonymous evolution comparable with that of the X chromosome. As autosomal heterogeneity cannot be owing to different times spent in the germ line, this demonstrates that the dominant determiner of synonymous rates of evolution is not, as has been conjectured, the time spent in the male germ line.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Claverton Downs, Bath, England. m.j.lercher@bath.ac.uk
authors.forename: M J
authors.initials: MJ
authors.lastname: Lercher
authors.forename: E J
authors.initials: EJ
authors.lastname: Williams
authors.forename: L D
authors.initials: LD
authors.lastname: Hurst
mesh_terms: D000818:Animals; D002874:Chromosome Mapping / Q000706:statistics & numerical data; D002875:Chromosomes / Q000235:genetics*; D019143:Evolution, Molecular; D020862:GC Rich Sequence / Q000235:genetics; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D051379:Mice; D009115:Muridae; D009154:Mutation / Q000235:genetics; D051381:Rats; D012641:Selection, Genetic; D012727:Sex Characteristics; D014960:X Chromosome / Q000235:genetics