Molecular Biology and Evolution. 21(2):410-417, FEBRUARY 2004
PMID: 14660686
Issn Print: 0737-4038
Publication Date: February 2004
A Gradient of Silent Substitution Rate in the Human Pseudoautosomal Region
Dmitry Filatov;Adam Eyre-Walker;
+ Author Information
School of Biosciences, University of Birmingham, Birmingham, United Kingdom
Abstract
It has been demonstrated that recombination in the human p-arm pseudoautosomal region (p-PAR) is at least twenty times more frequent than the genomic average of ∼1 cM/Mb, which may affect substitution patterns and rates in this region. Here I report the analysis of substitution patterns and rates in 10 human, chimpanzee, gorilla, and orangutan genes across the p-PAR. Between species silent divergence in the p-PAR forms a gradient, increasing toward the telomere. The correlation of silent divergence with distance from the p-PAR boundary is highly significant (ρ=0.911, P < 0.001). After exclusion of the CpG dinucleotides this correlation is still significant (ρ=0.89, P < 0.01), thus the substitution rate gradient cannot be explained solely by the differences in the extent of methylation across the p-PAR. Frequent recombination in the PAR may result in a relatively strong effect of biased gene conversion (BGC), which, because of the increased probability of fixation of the G or C nucleotides at (A or T)/(G or C) segregating sites, may affect substitution rates. BGC, however, does not seem to be the factor creating the substitution rate gradient in the p-PAR, because the only gradient is still detactable if only A↔T and G↔C substitutions are taken into account (ρ=0.82, P < 0.01). I hypothesize that the substitution rate gradient in the p-PAR is due to the mutagenic effect of recombination, which is very frequent in the distal human p-PAR and might be lower near the p-PAR boundary.
