Nature 351, 652 - 654 (20 June 1991); doi:10.1038/351652a0

Adaptive protein evolution at the Adh locus in Drosophila

John H. McDonald & Martin Kreitman

Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey 08544, USA

PROTEINS often differ in amino-acid sequence across species. This difference has evolved by the accumulation of neutral mutations by random drift, the fixation of adaptive mutations by selection, or a mixture of the two. Here we propose a simple statistical test of the neutral protein evolution hypothesis based on a comparison of the number of amino-acid replacement substitutions to synonymous substitutions in the coding region of a locus. If the observed substitutions are neutral, the ratio of replacement to synonymous fixed differences between species should be the same as the ratio of replacement to synonymous polymorphisms within species. DNA sequence data on the Adh locus (encoding alcohol dehydrogenase, EC 1.1.1.1) in three species in the Drosophila melanogaster species subgroup do not fit this expectation; instead, there are more fixed replacement differences between species than expected. We suggest that these excess replacement substitutions result from adaptive fixation of selectively advantageous mutations.

References

1.	Sokal, R. R. & Rohlf, F. J. Biometry (Freeman, San Francisco, 1981).
2.	Lewontin, R. C. A. Rev. Genet. 19, 81−102 (1985). | Article | ChemPort |
3.	Kreitman, M. & Hudson, R. R. Genetics 127, 565−582 (1991). | PubMed | ISI | ChemPort |
4.	Nei, M. Molecular Evolutionary Genetics (Columbia University Press, New York, 1987).
5.	Sharp, P. M. & Li, W.-H. J. molec. Evol. 28, 398−402 (1989). | PubMed | ChemPort |
6.	Kreitman, M. Nature 304, 412−417 (1983). | Article | PubMed | ISI | ChemPort |
7.	Haldane, J. B. S. J. Genet. 57, 511−524 (1957).
8.	Maynard Smith, J. Nature 219, 1114−1116 (1968). | PubMed | ChemPort |
9.	Sved, J. A. Am. Nat. 102, 283−293 (1968). | Article |
10.	Collet, C. J. molec. Evol. 27, 142−146 (1988). | PubMed | ChemPort |
11.	Bodmer, M. & Ashburner, M. Nature 309, 425−430 (1984). | Article | PubMed | ChemPort |
12.	Cohn, V. H. & Moore, G. P. Molec. Biol. Evol. 5, 154−166 (1988). | PubMed | ChemPort |
13.	Zagursky, R. J., Baumeister, K., Lomas, N. & Berman, M. L. Gene Analyt. Techn. 2, 89−94 (1985). | ChemPort |
14.	Saiki, R. K., Bugawan, T. L., Horn, G. T., Mullis, K. B. & Erlich, H. A. Nature 324, 163−166 (1988).
15.	Higuchi, R. G. & Ochman, H. Nucleic Acids Res. 17, 5865 (1989). | PubMed | ChemPort |