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
Mj. Lercher et al., 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, MOL BIOL EV, 18(11), 2001, pp. 2032-2039
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 nu
mber of cell divisions, then we expect that sequences on the X and Y chromo
somes and autosomes should mutate at different rates. Tests of this hypothe
sis for several mammalian species have led to conflicting results. At the s
ame time, recent evidence suggests that the chromosomal location of genes o
n autosomes affects their rate of evolution at synonymous sites. This sugge
sts a mutagenic source different from germ cell replication. To correctly i
nterpret the previous estimates of male mutation bias, it is crucial to und
erstand the degree and range of this local similarity. With a carefully cho
sen randomization protocol, local similarity in synonymous rates of evoluti
on can be detected in human-rodent and mouse-rat comparisons. However, the
synonymous-site similarity in the mouse-rat comparison remains weak. Simula
tions suggest that this difference between the mouse-human and the mouse-ra
t comparisons is not artifactual and that there is therefore a difference b
etween 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-rod
ent comparison was a methodological artifact). We show that Link-age effect
s have a long-range component: not one in a million random genomes shows su
ch levels of autosomal heterogeneity. The heterogeneity is so great that mo
re autosomes than expected by chance have rates of synonymous evolution com
parable with that of the X chromosome. As autosomal heterogeneity cannot be
owing to different times spent in the germ line, this demonstrates that th
e dominant determiner of synonymous rates of evolution is not, as has been
conjectured, the time spent in the male germ line.