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Comparative Study
. 2002 Sep;12(9):1350-6.
doi: 10.1101/gr.220502.

Deterministic mutation rate variation in the human genome

Nick G C Smith  1 , Matthew T Webster, Hans Ellegren
Affiliations
Comparative Study

Deterministic mutation rate variation in the human genome

Nick G C Smith et al. Genome Res. 2002 Sep.

Abstract

Several studies of substitution rate variation have indicated that the local mutation rate varies over the mammalian genome. In the present study, we show significant variation in substitution rates within the noncoding part of the human genome using 4.7 Mb of human-chimpanzee pairwise comparisons. Moreover, we find a significant positive covariation of lineage-specific chimpanzee and human local substitution rates, and very similar mean substitution rates down the two lineages. The substitution rate variation is probably not caused by selection or biased gene conversion, and so we conclude that mutation rates vary deterministically across the noncoding nonrepetitive regions of the human genome. We also show that noncoding substitution rates are significantly affected by G+C base composition, partly because the base composition is not at equilibrium.

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Figures

Figure 1
Figure 1
Histograms of human-chimpanzee distances with frequencies given by numbers of nonoverlapping 5-kb blocks. Distance distributions are plotted for all sequence data and for noncoding nonrepetitive sequences divided into intronic and intergenic classes.
Figure 2
Figure 2
Repeatability of primate nonrepetitive noncoding substitution rates shown by a positive correlation between human and chimpanzee lineage-specific distances. Distances are given as substitutions per nonoverlapping 5-kb block. Intergenic and intronic data are treated as separate data points.
Figure 3
Figure 3
Positive correlation between G+C content and substitution rates. G+C content is the human-chimpanzee average. Substitution rates are summed over human and chimpanzee lineages, with data points representing nonoverlapping 5-kb blocks from the human-chimp-baboon alignments. The line gives the linear regression of substitution rates against G+C content.
Figure 4
Figure 4
Compositional nonequilibrium in the nonrepetitive noncoding regions of the primate genome. The difference between the number of GC→AT substitutions and the number of AT→GC substitutions (expected to be zero at equilibrium) is plotted against G+C content. Data points represent nonoverlapping 5-kb blocks of intronic and intergenic sequence, with human and chimpanzee lineage-specific substitutions summed. The line gives the linear regression, indicating the bias at high GC.
Figure 5
Figure 5
Mutation rates per base pair against G+C content for GC→AT (open circles) and AT→GC (closed circles) mutations. Data points represent nonoverlapping 5-kb blocks of intronic and intergenic sequence, with human and chimpanzee lineage-specific substitutions summed. The lines give linear regressions (dashed for GC→AT, solid for AT→GC).
See this image and copyright information in PMC

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