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Mol. Biol. Evol. 20(2):278-286. 2003
DOI: 10.1093/molbev/msg037
© 2003 by the Society for Molecular Biology and Evolution. ISSN: 0737-4038

Compositional Evolution of Noncoding DNA in the Human and Chimpanzee Genomes

Matthew T. Webster, Nick G. C. Smith and Hans Ellegren

Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden

We have examined the compositional evolution of noncoding DNA in the primate genome by comparison of lineage-specific substitutions observed in 1.8 Mb of genomic alignments of human, chimpanzee, and baboon with 6542 human single-nucleotide polymorphisms (SNPs) rooted using chimpanzee sequence. The pattern of compositional evolution, measured in terms of the numbers of GC->AT and AT->GC changes, differs significantly between fixed and polymorphic sites, and indicates that there is a bias toward fixation of AT->GC mutations, which could result from weak directional selection or biased gene conversion in favor of high GC content. Comparison of the frequency distributions of a subset of the SNPs revealed no significant difference between GC->AT and AT->GC polymorphisms, although AT->GC polymorphisms in regions of high GC segregate at slightly higher frequencies on average than GC->AT polymorphisms, which is consistent with a fixation bias favoring high GC in these regions. However, the substitution data suggest that this fixation bias is relatively weak, because the compositional structure of the human and chimpanzee genomes is becoming homogenized, with regions of high GC decreasing in GC content and regions of low GC increasing in GC content. The rate and pattern of nucleotide substitution in 333 Alu repeats within the human-chimpanzee-baboon alignments are not significantly affected by the GC content of the region in which they are inserted, providing further evidence that, since the time of the human-chimpanzee ancestor, there has been little or no regional variation in mutation bias.

Key Words: isochore • base composition • human • chimpanzee • selection • SNP


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