Abstract
Associations between selected alleles and the genetic backgrounds on which they are found can reduce the efficacy of selection. We consider the extent to which such interference, known as the Hill-Robertson effect, acting between weakly selected alleles, can restrict molecular adaptation and affect patterns of polymorphism and divergence. In particular, we focus on synonymous-site mutations, considering the fate of novel variants in a two-locus model and the equilibrium effects of interference with multiple loci and reversible mutation. We find that weak selection Hill-Robertson (wsHR) interference can considerably reduce adaptation, e.g., codon bias, and, to a lesser extent, levels of polymorphism, particularly in regions of low recombination. Interference causes the frequency distribution of segregating sites to resemble that expected from more weakly selected mutations and also generates specific patterns of linkage disequilibrium. While the selection coefficients involved are small, the fitness consequences of wsHR interference across the genome can be considerable. We suggest that wsHR interference is an important force in the evolution of nonrecombining genomes and may explain the unexpected constancy of codon bias across species of very different census population sizes, as well as several unusual features of codon usage in Drosophila.
Full Text
The Full Text of this article is available as a PDF (397.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Akashi H. Inferring the fitness effects of DNA mutations from polymorphism and divergence data: statistical power to detect directional selection under stationarity and free recombination. Genetics. 1999 Jan;151(1):221–238. doi: 10.1093/genetics/151.1.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Akashi H., Schaeffer S. W. Natural selection and the frequency distributions of "silent" DNA polymorphism in Drosophila. Genetics. 1997 May;146(1):295–307. doi: 10.1093/genetics/146.1.295. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ballard J. W., Kreitman M. Unraveling selection in the mitochondrial genome of Drosophila. Genetics. 1994 Nov;138(3):757–772. doi: 10.1093/genetics/138.3.757. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barton N. H. Linkage and the limits to natural selection. Genetics. 1995 Jun;140(2):821–841. doi: 10.1093/genetics/140.2.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bauer V. L., Aquadro C. F. Rates of DNA sequence evolution are not sex-biased in Drosophila melanogaster and D. simulans. Mol Biol Evol. 1997 Dec;14(12):1252–1257. doi: 10.1093/oxfordjournals.molbev.a025734. [DOI] [PubMed] [Google Scholar]
- Begun D. J., Aquadro C. F. Levels of naturally occurring DNA polymorphism correlate with recombination rates in D. melanogaster. Nature. 1992 Apr 9;356(6369):519–520. doi: 10.1038/356519a0. [DOI] [PubMed] [Google Scholar]
- Birky C. W., Jr, Walsh J. B. Effects of linkage on rates of molecular evolution. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6414–6418. doi: 10.1073/pnas.85.17.6414. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Braverman J. M., Hudson R. R., Kaplan N. L., Langley C. H., Stephan W. The hitchhiking effect on the site frequency spectrum of DNA polymorphisms. Genetics. 1995 Jun;140(2):783–796. doi: 10.1093/genetics/140.2.783. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bulmer M. The selection-mutation-drift theory of synonymous codon usage. Genetics. 1991 Nov;129(3):897–907. doi: 10.1093/genetics/129.3.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Charlesworth B. The effect of background selection against deleterious mutations on weakly selected, linked variants. Genet Res. 1994 Jun;63(3):213–227. doi: 10.1017/s0016672300032365. [DOI] [PubMed] [Google Scholar]
- Charlesworth D., Charlesworth B., Morgan M. T. The pattern of neutral molecular variation under the background selection model. Genetics. 1995 Dec;141(4):1619–1632. doi: 10.1093/genetics/141.4.1619. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chiapello H., Lisacek F., Caboche M., Hénaut A. Codon usage and gene function are related in sequences of Arabidopsis thaliana. Gene. 1998 Mar 16;209(1-2):GC1–GC38. doi: 10.1016/s0378-1119(97)00671-9. [DOI] [PubMed] [Google Scholar]
- Comeron J. M., Kreitman M., Aguadé M. Natural selection on synonymous sites is correlated with gene length and recombination in Drosophila. Genetics. 1999 Jan;151(1):239–249. doi: 10.1093/genetics/151.1.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Duret L., Mouchiroud D. Expression pattern and, surprisingly, gene length shape codon usage in Caenorhabditis, Drosophila, and Arabidopsis. Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4482–4487. doi: 10.1073/pnas.96.8.4482. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eyre-Walker A., Bulmer M. Synonymous substitution rates in enterobacteria. Genetics. 1995 Aug;140(4):1407–1412. doi: 10.1093/genetics/140.4.1407. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fu Y. X., Li W. H. Statistical tests of neutrality of mutations. Genetics. 1993 Mar;133(3):693–709. doi: 10.1093/genetics/133.3.693. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haigh J. The accumulation of deleterious genes in a population--Muller's Ratchet. Theor Popul Biol. 1978 Oct;14(2):251–267. doi: 10.1016/0040-5809(78)90027-8. [DOI] [PubMed] [Google Scholar]
- Hartl D. L., Moriyama E. N., Sawyer S. A. Selection intensity for codon bias. Genetics. 1994 Sep;138(1):227–234. doi: 10.1093/genetics/138.1.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hill W. G., Robertson A. The effect of linkage on limits to artificial selection. Genet Res. 1966 Dec;8(3):269–294. [PubMed] [Google Scholar]
- Kimura M., Maruyama T. The mutational load with epistatic gene interactions in fitness. Genetics. 1966 Dec;54(6):1337–1351. doi: 10.1093/genetics/54.6.1337. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kimura M. Theoretical foundation of population genetics at the molecular level. Theor Popul Biol. 1971 Jun;2(2):174–208. doi: 10.1016/0040-5809(71)90014-1. [DOI] [PubMed] [Google Scholar]
- Kliman R. M., Hey J. Reduced natural selection associated with low recombination in Drosophila melanogaster. Mol Biol Evol. 1993 Nov;10(6):1239–1258. doi: 10.1093/oxfordjournals.molbev.a040074. [DOI] [PubMed] [Google Scholar]
- Kondrashov A. S. Contamination of the genome by very slightly deleterious mutations: why have we not died 100 times over? J Theor Biol. 1995 Aug 21;175(4):583–594. doi: 10.1006/jtbi.1995.0167. [DOI] [PubMed] [Google Scholar]
- Krone SM, Neuhauser C. Ancestral Processes with Selection. Theor Popul Biol. 1997 Jun;51(3):210–237. doi: 10.1006/tpbi.1997.1299. [DOI] [PubMed] [Google Scholar]
- Lynch M., Blanchard J. L. Deleterious mutation accumulation in organelle genomes. Genetica. 1998;102-103(1-6):29–39. [PubMed] [Google Scholar]
- Lynch M. Mutation accumulation in nuclear, organelle, and prokaryotic transfer RNA genes. Mol Biol Evol. 1997 Sep;14(9):914–925. doi: 10.1093/oxfordjournals.molbev.a025834. [DOI] [PubMed] [Google Scholar]
- Moran N. A. Accelerated evolution and Muller's rachet in endosymbiotic bacteria. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2873–2878. doi: 10.1073/pnas.93.7.2873. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moriyama E. N., Powell J. R. Gene length and codon usage bias in Drosophila melanogaster, Saccharomyces cerevisiae and Escherichia coli. Nucleic Acids Res. 1998 Jul 1;26(13):3188–3193. doi: 10.1093/nar/26.13.3188. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moriyama E. N., Powell J. R. Intraspecific nuclear DNA variation in Drosophila. Mol Biol Evol. 1996 Jan;13(1):261–277. doi: 10.1093/oxfordjournals.molbev.a025563. [DOI] [PubMed] [Google Scholar]
- Nachman M. W. Deleterious mutations in animal mitochondrial DNA. Genetica. 1998;102-103(1-6):61–69. [PubMed] [Google Scholar]
- Otto S. P., Barton N. H. The evolution of recombination: removing the limits to natural selection. Genetics. 1997 Oct;147(2):879–906. doi: 10.1093/genetics/147.2.879. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Powell J. R., Moriyama E. N. Evolution of codon usage bias in Drosophila. Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):7784–7790. doi: 10.1073/pnas.94.15.7784. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Price G. R. Selection and covariance. Nature. 1970 Aug 1;227(5257):520–521. doi: 10.1038/227520a0. [DOI] [PubMed] [Google Scholar]
- Przeworski M., Charlesworth B., Wall J. D. Genealogies and weak purifying selection. Mol Biol Evol. 1999 Feb;16(2):246–252. doi: 10.1093/oxfordjournals.molbev.a026106. [DOI] [PubMed] [Google Scholar]
- Santiago E., Caballero A. Effective size and polymorphism of linked neutral loci in populations under directional selection. Genetics. 1998 Aug;149(4):2105–2117. doi: 10.1093/genetics/149.4.2105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Santiago E., Caballero A. Effective size of populations under selection. Genetics. 1995 Feb;139(2):1013–1030. doi: 10.1093/genetics/139.2.1013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sawyer S. A., Hartl D. L. Population genetics of polymorphism and divergence. Genetics. 1992 Dec;132(4):1161–1176. doi: 10.1093/genetics/132.4.1161. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sharp P. M., Li W. H. An evolutionary perspective on synonymous codon usage in unicellular organisms. J Mol Evol. 1986;24(1-2):28–38. doi: 10.1007/BF02099948. [DOI] [PubMed] [Google Scholar]
- Sharp P. M., Tuohy T. M., Mosurski K. R. Codon usage in yeast: cluster analysis clearly differentiates highly and lowly expressed genes. Nucleic Acids Res. 1986 Jul 11;14(13):5125–5143. doi: 10.1093/nar/14.13.5125. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shields D. C., Sharp P. M., Higgins D. G., Wright F. "Silent" sites in Drosophila genes are not neutral: evidence of selection among synonymous codons. Mol Biol Evol. 1988 Nov;5(6):704–716. doi: 10.1093/oxfordjournals.molbev.a040525. [DOI] [PubMed] [Google Scholar]
- Smith J. M., Haigh J. The hitch-hiking effect of a favourable gene. Genet Res. 1974 Feb;23(1):23–35. [PubMed] [Google Scholar]
- Smith J. M., Smith N. H., O'Rourke M., Spratt B. G. How clonal are bacteria? Proc Natl Acad Sci U S A. 1993 May 15;90(10):4384–4388. doi: 10.1073/pnas.90.10.4384. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stenico M., Lloyd A. T., Sharp P. M. Codon usage in Caenorhabditis elegans: delineation of translational selection and mutational biases. Nucleic Acids Res. 1994 Jul 11;22(13):2437–2446. doi: 10.1093/nar/22.13.2437. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Watterson G. A. On the number of segregating sites in genetical models without recombination. Theor Popul Biol. 1975 Apr;7(2):256–276. doi: 10.1016/0040-5809(75)90020-9. [DOI] [PubMed] [Google Scholar]
- Wright S. Evolution in Mendelian Populations. Genetics. 1931 Mar;16(2):97–159. doi: 10.1093/genetics/16.2.97. [DOI] [PMC free article] [PubMed] [Google Scholar]