Inferring Weak Selection From Patterns of Polymorphism and Divergence at ``Silent'' Sites in Drosophila DNA

INVESTIGATIONS

Inferring Weak Selection From Patterns of Polymorphism and Divergence at ``Silent'' Sites in Drosophila DNA

H. Akashi
Department of Ecology and Evolution, University of Chicago, Chicago, Illinois 60637

Patterns of codon usage and ``silent'' DNA divergence suggest that natural selection discriminates among synonymous codons in Drosophila. ``Preferred'' codons are consistently found in higher frequencies within their synonymous families in Drosophila melanogaster genes. This suggests a simple model of silent DNA evolution where natural selection favors mutations from unpreferred to preferred codons (preferred changes). Changes in the opposite direction, from preferred to unpreferred synonymous codons (unpreferred changes), are selected against. Here, selection on synonymous DNA mutations is investigated by comparing the evolutionary dynamics of these two categories of silent DNA changes. Sequences from outgroups are used to determine the direction of synonymous DNA changes within and between D. melanogaster and Drosophila simulans for five genes. Population genetics theory shows that differences in the fitness effect of mutations can be inferred from the comparison of ratios of polymorphism to divergence. Unpreferred changes show a significantly higher ratio of polymorphism to divergence than preferred changes in the D. simulans lineage, confirming the action of selection at silent sites. An excess of unpreferred fixations in 28 genes suggests a relaxation of selection on synonymous mutations in D. melanogaster. Estimates of selection coefficients for synonymous mutations (3.6 <|N(e)s| < 1.3) in D. simulans are consistent with the reduced efficacy of natural selection (|N(e)s| < 1) in the three- to sixfold smaller effective population size of D. melanogaster. Synonymous DNA changes appear to be a prevalent class of weakly selected mutations in Drosophila.

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				K. R. Thornton and J. D. Jensen Controlling the False-Positive Rate in Multilocus Genome Scans for Selection Genetics, February 1, 2007; 175(2): 737 - 750. [Abstract] [Full Text] [PDF]

				R. Nielsen, V. L. Bauer DuMont, M. J. Hubisz, and C. F. Aquadro Maximum Likelihood Estimation of Ancestral Codon Usage Bias Parameters in Drosophila Mol. Biol. Evol., January 1, 2007; 24(1): 228 - 235. [Abstract] [Full Text] [PDF]

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				C. Bartolome and B. Charlesworth Evolution of Amino-Acid Sequences and Codon Usage on the Drosophila miranda Neo-Sex Chromosomes Genetics, December 1, 2006; 174(4): 2033 - 2044. [Abstract] [Full Text] [PDF]

				A. D. Cutter, J. D. Wasmuth, and M. L. Blaxter The Evolution of Biased Codon and Amino Acid Usage in Nematode Genomes Mol. Biol. Evol., December 1, 2006; 23(12): 2303 - 2315. [Abstract] [Full Text] [PDF]

				D. C. Presgraves Intron Length Evolution in Drosophila Mol. Biol. Evol., November 1, 2006; 23(11): 2203 - 2213. [Abstract] [Full Text] [PDF]

				W.-Y. Ko, S. Piao, and H. Akashi Strong Regional Heterogeneity in Base Composition Evolution on the Drosophila X Chromosome Genetics, September 1, 2006; 174(1): 349 - 362. [Abstract] [Full Text] [PDF]

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