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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 versus 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 fourfold redundant sites is consistently elevated above the neutral expectation—more so than for any other class of sites.

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Support was provided by the Multidisciplinary University Research Initiative awards W911NF-09-1-0444 and W911NF-14-1-0411 from the US Army Research Office to M.L., National Institutes of Health awards R01-GM036827 and R35-GM122566 to M.L., National Natural Science Foundation of China 31741071 to H.L., R01-GM51986 and R35-GM122556 to Y.V.B., F32-GM083581 to D.T.K. and National Science Foundation grant DOB 1442246 to J.T.L. We thank T. G. Doak, P. Keightley, K. Morris, R. Ness, I. Ruiz-Trillo, S. Simpson, W. K. Thomas, A. Uchimura and Z. Ye for providing strains and/or technical help in data acquisition. We thank L. Duret for helpful comments.

Author information

H.L., W.S., and M.L. conceived and designed the study, performed the data analyses and wrote the manuscript. All authors contributed to data collection and provided input to the manuscript.

Competing interests

The authors declare no competing financial interests.

Correspondence to Michael Lynch.

Supplementary information

  1. Supplementary Tables 1–6

    Table 1 shows details of mutation datasets used in this study. Tables 2 and 3 list mutations from 12 microbial organisms that are first reported here. Table 4 shows results of linear regressions involving genome G/C content vs the expectations based on mutation bias. Table 5 gives parameters from regressions of selection coefficients at different genomic sites, as well as those of selection coefficients vs the mutation bias m. Table 6 shows the relationship between expression level and G/C content within 17 organisms.

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Fig. 1: Relationship between genome-wide nucleotide composition and the neutral expectation.
Fig. 2: Expected equilibrium levels of within-population nucleotide diversity scaled by the neutral expectation.