Evolutionary determinants of genome-wide nucleotide composition

Abstract

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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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.

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Acknowledgements

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.

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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.

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Correspondence to Michael Lynch.

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The authors declare no competing financial interests.

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Supplementary information

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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Long, H., Sung, W., Kucukyildirim, S. et al. Evolutionary determinants of genome-wide nucleotide composition. Nat Ecol Evol 2, 237–240 (2018). https://doi.org/10.1038/s41559-017-0425-y

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