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MBE Advance Access published online on March 19, 2004

Molecular Biology and Evolution, doi:10.1093/molbev/msh128
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2004; all rights reserved
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Accepted February 23, 2004
© 2004 Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2004; all rights reserved.

Original Articles

Common Pattern of Evolution of Gene Expression Level and Protein Sequence in Drosophila

Sergey V. Nuzhdin 1*, Marta L. Wayne 2, Kristy L. Harmon 1, and Lauren M. McIntyre 3

1 Evolution and Ecology, University of California at Davis, Davis, CA 95616
2 Department of Zoology, University of Florida, Gainesville, FL 32611
3 Computational Genomics, Purdue University, West Lafayette IN, 47905

* To whom correspondence should be addressed. E-mail: svnuzhdin{at}ucdavis.edu.


   Abstract

Sequence divergence scaled by variation within species has been used to infer the action of selection upon individual genes. Applying this approach to expression, we compared whole genome whole body RNA levels in ten heterozygous Drosophila simulans genotypes and a pooled sample of ten D. melanogaster lines using Affymetrix Genechips ®. For 972 genes expressed in D. melanogaster, the transcript level was below detection threshold in D. simulans, which may be explained either by sequence divergence between the primers on the chip and the mRNA transcripts, or by down-regulation of these genes. Out of 6,707 genes which were expressed in both species, transcript level was significantly different between species for 534 genes (at P < 0.001). Genes whose expression is under stabilizing selection should exhibit reduced genetic variation within species and reduced divergence between species. Expression of genes under directional selection in D. simulans should be highly divergent from D. melanogaster, while showing low genetic variation in D. simulans. Finally, the genes with large variation within species, but modest divergence between species, are candidates for balancing selection. Rapidly diverging, low polymorphism genes included those involved in reproduction - for instance Mst 3Ba, 98Cb; Acps 26Aa, 63F; and sperm specific dynein. Genes with high variation in transcript abundance within species included metallothionein and hairless, both hypothesized to be segregating in nature due to gene by environment interactions. Further, we compared expression divergence and DNA substitution rate in 195 genes. Synonymous substitution rate and expression divergences were uncorrelated, while there was a significant positive correlation between non-synonymous substitution rate and expression divergence. We hypothesize that as a substantial fraction of non-synonymous divergence has been shown to be adaptive, much of the observed expression divergence is likewise adaptive.

Key Words: gene expression, DNA microarrays, sequence divergence, selection


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