Evidence of selection on silent site base composition in mammals: Potential implications for the evolution of isochores and junk DNA

It has been suggested that mutation bias is the major de terminant of base composition bias at synonymous, intron, and flanking DNA sites in mammals. Here I test this hypothesis using population genetic data from the major hi stocompatibility genes of several mammalian species. The results of two tes ts are inconsistent with the mutation hypothesis in coding, noncoding, CpG- island, and non-CpG-island DNA, but are consistent with selection or biased gene conversion. It is argued that biased gene conversion is unlikely to a ffect silent site base composition in mammals. The results therefore sugges t that selection is acting upon silent site G + C content. This may have br oad implications, since silent site base composition reflects large-scale v ariation in G + C content along mammalian chromosomes. The results therefor e suggest that selection may be acting upon the base composition of isochor es and large sections of junk DNA.