Journal
MOLECULAR BIOLOGY AND EVOLUTION
Volume 24, Issue 10, Pages 2196-2202Publisher
OXFORD UNIV PRESS
DOI: 10.1093/molbev/msm149
Keywords
ancestral misidentification; biased gene conversion; context dependence; GC-content; human; natural selection; single nucleotide polymorphism; site-frequency spectrum
Ask authors/readers for more resources
Understanding the proximate and ultimate causes underlying the evolution of nucleotide composition in mammalian genomes is of fundamental interest to the study of molecular evolution. Comparative genomics studies have revealed that many more substitutions occur from G and C nucleotides to A and T nucleotides than the reverse, suggesting that mammalian genomes are not at equilibrium for base composition. Analysis of human polymorphism data suggests that mutations that increase GC-content tend to be at much higher frequencies than those that decrease or preserve GC-content when the ancestral allele is inferred via parsimony using the chimpanzee genome. These observations have been interpreted as evidence for a fixation bias in favor of G and C alleles due to either positive natural selection or biased gene conversion. Here, we test the robustness of this interpretation to violations of the parsimony assumption using a data set of 21,488 noncoding single nucleotide polymorphisms (SNPs) discovered by the National Institute of Environmental Health Sciences (NIEHS) SNPs project via direct resequencing of n = 95 individuals. Applying standard nonparametric and parametric population genetic approaches, we replicate the signatures of a fixation bias in favor of G and C alleles when the ancestral base is assumed to be the base found in the chimpanzee outgroup. However, upon taking into account the probability of misidentifying the ancestral state of each SNP using a context-dependent mutation model, the corrected distribution of SNP frequencies for GC-content increasing SNPs are nearly indistinguishable from the patterns observed for other types of mutations, suggesting that the signature of fixation bias is a spurious artifact of the parsimony assumption.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available