Comparison of the gene-expression profiles between adults of Drosophila melanogaster and Drosophila simulans has uncovered the evolution of genes that exhibit sex-dependent regulation. Approximately half the genes showed differences in expression between the species, and among these, approximately 83% involved a gain, loss, increase, decrease, or reversal of sex-biased expression. Most of the interspecific differences in messenger RNA abundance affect male-biased genes. Genes that differ in expression between the species showed functional clustering only if they were sex-biased. Our results suggest that sex-dependent selection may drive changes in expression of many of the most rapidly evolving genes in the Drosophila transcriptome.

Transcription is a slow and expensive process: in eukaryotes, approximately 20 nucleotides can be transcribed per second at the expense of at least two ATP molecules per nucleotide. Thus, at least for highly expressed genes, transcription of long introns, which are particularly common in mammals, is costly. Using data on the expression of genes that encode proteins in Caenorhabditis elegans and Homo sapiens, we show that introns in highly expressed genes are substantially shorter than those in genes that are expressed at low levels. This difference is greater in humans, such that introns are, on average, 14 times shorter in highly expressed genes than in genes with low expression, whereas in C. elegans the difference in intron length is only twofold. In contrast, the density of introns in a gene does not strongly depend on the level of gene expression. Thus, natural selection appears to favor short introns in highly expressed genes to minimize the cost of transcription and other molecular processes, such as splicing.

GeneMerge is available free of charge for academic use over the web and for download from: http://www.oeb.harvard.edu/hartl/lab/publications/GeneMerge.html.

The relationship between protein and regulatory sequence evolution is a central question in molecular evolution. It is currently not known to what extent changes in gene expression are coupled with the evolution of protein coding sequences, or whether these changes differ among orthologs (species homologs) and paralogs (duplicate genes). Here, we develop a method to measure the extent of functionally relevant cis-regulatory sequence change in homologous genes, and validate it using microarray data and experimentally verified regulatory elements in different eukaryotic species. By comparing the genomes of Caenorhabditis elegans and C. briggsae, we found that protein and regulatory evolution is weakly coupled in orthologs but not paralogs, suggesting that selective pressure on gene expression and protein evolution is quite similar and persists for a significant amount of time following speciation but not gene duplication. Additionally, duplicates of both species exhibit a dramatic acceleration of both regulatory and protein evolution compared to orthologs, suggesting increased directional selection and/or relaxed selection on both gene expression patterns and protein function in duplicate genes.[Supplemental material is available online at www.genome.org.]The relative importance of coding sequence change versus regulatory sequence change in evolution has vexed evolutionary geneticists for over 50 years. Given recent genomic analyses showing the conservation of many proteins among distantly related taxa, it has been proposed that regulatory changes play a key role in generating the great morphological diversity present in multicellular species. However, little is known about the evolution of gene regulation or its relationship to protein evolution. Do highly conserved genes also show conserved expression patterns? Or can gene expression evolve independently from protein function? The former pattern is expected if strong stabilizing selection acts on genes as integrated units in which protein sequence and expression pattern are not dissociable. At the same time it has been argued that "developmental systems drift" may result in reorganization of regulatory systems as long as general developmental patterns are preserved (True and Haag 2001). If so, a high turnover of gene regulatory elements may uncouple cis-elementmediated gene expression and protein evolution.Differences in gene expression between species (or between duplicate genes) may entail changes in gene expression levels under the same conditions at the same developmental times, as well as gene expression changes in spatial, temporal, and environmental dimensions. Hereafter, we refer to the former changes as changes in expression magnitude and the latter as changes in relative expression. First attempts to find a correlation between the evolution of relative expression and protein evolution in yeast (using only duplicates) yielded contradictory results; one study argued that expression differences are not correlated with protein evolution (Wagner 2000), wher...

We compare the functional spectrum of protein evolution in two separate animal lineages with respect to two hypotheses: (1) rates of divergence are distributed similarly among functional classes within both lineages, indicating that selective pressure on the proteome is largely independent of organismic-level biological requirements; and (2) rates of divergence are distributed differently among functional classes within each lineage, indicating species-specific selective regimes impact genome-wide substitutional patterns. Integrating comparative genome sequence with data from tissue-specific expressed-sequence-tag (EST) libraries and detailed database annotations, we find a functional genomic signature of rapid evolution and selective constraint shared between mammalian and nematode lineages despite their extensive morphological and ecological differences and distant common ancestry. In both phyla, we find evidence of accelerated evolution among components of molecular systems involved in coevolutionary change. In mammals, lineage-specific fast evolving genes include those involved in reproduction, immunity, and possibly, maternal–fetal conflict. Likelihood ratio tests provide evidence for positive selection in these rapidly evolving functional categories in mammals. In contrast, slowly evolving genes, in terms of amino acid or insertion/deletion (indel) change, in both phyla are involved in core molecular processes such as transcription, translation, and protein transport. Thus, strong purifying selection appears to act on the same core cellular processes in both mammalian and nematode lineages, whereas positive and/or relaxed selection acts on different biological processes in each lineage

It has been hypothesized that evolutionary changes will be more frequent in later ontogeny than early ontogeny because of developmental constraint. To test this hypothesis, a genomewide examination of molecular evolution through ontogeny was carried out using comparative genomic data in Caenorhabditis elegans and Caenorhabditis briggsae. We found that the mean rate of amino acid replacement is not significantly different between genes expressed during and after embryogenesis. However, synonymous substitution rates differed significantly between these two classes. A genomewide survey of correlation between codon bias and expression level found codon bias to be significantly correlated with mRNA expression (r(s) = -0.30 and P < 10(-131)) but does not alone explain differences in dS between classes. Surprisingly, it was found that genes expressed after embryogenesis have a significantly greater number of duplicates in both the C. elegans and C. briggsae genomes (P < 10(-20) and P < 10(-13)) when compared with early-expressed and nonmodulated genes. A similarity in the distribution of duplicates of nonmodulated and early-expressed genes, as well as a disproportionately higher number of early pseudogenes, lend support to the hypothesis that this difference in duplicate number is caused by selection against gene duplicates of early-expressed genes, reflecting developmental constraint. Developmental constraint at the level of gene duplication may have important implications for macroevolutionary change.

Very little is known about molecular evolution in the human malaria parasite Plasmodium falciparum. Given the potentially important role that introns play in directing transcription and the posttranscriptional control of gene expression, we compare rates of intron/gain loss and intronic substitution in P. falciparum and the rodent malaria P. y. yoelii in both orthologous and duplicate genes. Specifically, we test the hypothesis that intron gain/loss and protein evolution is accelerated in duplicate genes versus orthologous genes in both parasites using the genome sequence of both species. We find that duplicate genes in both P. falciparum and P. y. yoelii exhibit a dramatic acceleration of both intron gain/loss and protein evolution in comparison with orthologs, suggesting increased directional and/or relaxed selection in duplicate genes. Further, we find that rates of intron gain/loss and protein evolution are weakly coupled in orthologs but not paralogs, supporting the hypothesis that selection acts on genes as functionally integrated units after speciation but not necessarily after gene duplication. In contrast, we find that rates of nucleotide substitution do not differ significantly between intronic sites and synonymous sites among duplicate genes, implying that a large fraction of intronic sites in Plasmodium evolve under little or no selective constraint.

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