Evolution of the isochore structure in the scale of chromosome: Insight from the mutation bias and fixation bias

Abstract

Following the development of reliable methods for inferring the direction of mutations of the single nucleotide polymorphism (SNP), and the revealing of the human isochore map, it has become possible to investigate the evolution of the isochore structure in a continuous region. In this study, the recent evolution of the isochore structure on human chromosome 18, as inferred from the SNP, was examined. A remarkable mutation bias was found, which was destroying the present isochore structure. However, a fixation bias contributed by the biased gene conversion (BGC) effect and a rising fixation probability of derived alleles with increasing GC content was extending the present isochore structure. Combining the two opposing processes, the old isochore structure was declining and a more homogenous isochore structure with higher GC content was being formed on the chromosome. During this process, both the CpG and genic sites, which were present in the isochore but were paid little attention to before, played an important role. In addition, the recombination was confirmed to promote the GC alleles fixed in the genome because of the BGC effect. For the first time, it was observed that with the occurrence of little recombination, AT alleles had the identical fixation probability with GC alleles in the recombination cold spots. © 2007 The Authors.