Evolutionary determinants of genome-wide nucleotide composition

One of the long-standing mysteries of evolutionary genomics is the source of the wide phylogenetic diversity in genome nucleotide composition (G+C vs. A+T), which must be a consequence of interspecific differences in mutation bias, the efficiency of selection for different nucleotides, or a combination of the two. We demonstrate that although genomic G+C composition is strongly driven by mutation bias, it is also substantially modified by direct selection and/or as a by-product of biased gene conversion. Moreover, G+C composition at four-fold redundant sites is consistently elevated above the neutral expectation, more so than for any other classes of sites.