Accelerated sequence divergence of conserved genomic elements in Drosophila melanogaster

Department of Evolution and Ecology and Center for Population Biology, University of California, Davis, California 95691, USA.
Genome Research (Impact Factor: 14.63). 07/2008; 18(10):1592-601. DOI: 10.1101/gr.077131.108
Source: PubMed


Recent genomic sequencing of 10 additional Drosophila genomes provides a rich resource for comparative genomics analyses aimed at understanding the similarities and differences between species and between Drosophila and mammals. Using a phylogenetic approach, we identified 64 genomic elements that have been highly conserved over most of the Drosophila tree, but that have experienced a recent burst of evolution along the Drosophila melanogaster lineage. Compared to similarly defined elements in humans, these regions of rapid lineage-specific evolution in Drosophila differ dramatically in location, mechanism of evolution, and functional properties of associated genes. Notably, the majority reside in protein-coding regions and primarily result from rapid adaptive synonymous site evolution. In fact, adaptive evolution appears to be driving substitutions to unpreferred codons. Our analysis also highlights interesting noncoding genomic regions, such as regulatory regions in the gene gooseberry-neuro and a putative novel miRNA.

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    • "Previous analyses of D. melanogaster divergence suggested the possibility that AT mutations may be favored in this species (Holloway et al. 2008; Bauer DuMont et al. 2009). Our analysis of divergence supports the conclusion of Bauer Dumont et al. (2009) that AT-biased substitution is positively correlated with recombination. "
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    ABSTRACT: The relative importance of mutation, selection, and biased gene conversion to patterns of base composition variation in Drosophila melanogaster and to a lesser extent, D. simulans, has been investigated for many years. However, genomic data from sufficiently large samples to thoroughly characterize patterns of base composition polymorphism within species have been lacking. Here, we report a genome-wide analysis of coding and noncoding polymorphism in a large sample of inbred D. melanogaster strains from Raleigh, North Carolina. Consistent with previous results, we observed that AT mutations fix more frequently than GC mutations in D. melanogaster. Contrary to predictions of previous models of codon usage in D. melanogaster, we found that synonymous sites segregating for derived AT polymorphisms were less skewed towards low frequencies compared to sites segregating a derived GC polymorphism. However, no such pattern was observed for comparable base composition polymorphisms in noncoding DNA. These results suggest that AT-ending codons could currently be favored by natural selection in the D. melanogaster lineage.
    Genome Biology and Evolution 11/2012; 4(12). DOI:10.1093/gbe/evs097 · 4.23 Impact Factor
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    • "Rates of evolution vary not only between proteins but also between different sites within a single protein, and many factors have been proposed to account for this variation, such as distance from functional sites (Dean et al. 2002), base composition (Bernardi 2005), codon usage (Bulmer 1991; Bernardi 2005; Holloway et al. 2008; Yang and Nielsen 2008), and degree of solvent exposure (Hughes and Nei 1988; Benach et al. 2000; Bishop et al. 2000; Dean et al. 2002; Lin et al. 2007). Functional residues are often the most conserved regions of the protein (Benach et al. 2000; Dean et al. 2002; O'Farrell et al. 2008), and solvent-exposed residues are the most changeable. "
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    ABSTRACT: Different protein secondary structure elements have different physicochemical properties and roles in the protein, which may determine their evolutionary flexibility. However, it is not clear to what extent protein structure affects the way Darwinian selection acts at the amino acid level. Using phylogeny-based likelihood tests for positive selection, we have examined the relationship between protein secondary structure and selection across six species of Drosophila. We find that amino acids that form disordered regions, such as random coils, are far more likely to be under positive selection than expected from their proportion in the proteins, and residues in helices and beta-structures are subject to less positive selection than predicted. In addition, it appears that sites undergoing positive selection are more likely than expected to occur close to one another in the protein sequence. Finally, on a genome-wide scale, we have determined that positively selected sites are found more frequently toward the gene ends. Our results demonstrate that protein structures with a greater degree of organization and strong hydrophobicity, represented here as helices and beta-structures, are less tolerant to molecular adaptation than disordered, hydrophilic regions, across a diverse set of proteins.
    Genome Biology and Evolution 05/2010; 2(1):166-79. DOI:10.1093/gbe/evq008 · 4.23 Impact Factor
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    • "Given that the pattern of substitution in D. sechellia more closely resembles that of the most recent common ancestor between these species (Singh N, Arndt P, Clark A, and Aquadro C, personal communication); another hypothesis is that synonymous sites have responded more quickly to a change in selective or nonselective pressures on base composition along the D. melanogaster lineage. In particular, the between-chromosome comparisons suggest the existence of a fixation bias toward A and T as has previously been suggested for this species (e.g., Bauer DuMont et al. 2004; Holloway et al. 2008). "
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    ABSTRACT: Selection is thought to be partially responsible for patterns of molecular evolution at synonymous sites within numerous Drosophila species. Recently, “per-site” and likelihood methods have been developed to detect loci for which positive selection is a major component of synonymous site evolution. An underlying assumption of these methods, however, is a homogeneous mutation process. To address this potential shortcoming, we perform a complementary analysis making gene-by-gene comparisons of paired synonymous site and intron substitution rates toward and away from the nucleotides G and C because preferred codons are G or C ending in Drosophila. This comparison may reduce both the false-positive rate (due to broadscale heterogeneity in mutation) and false-negative rate (due to lack of power comparing small numbers of sites) of the per-site and likelihood methods. We detect loci with patterns of evolution suggestive of synonymous site selection pressures predominately favoring unpreferred and preferred codons along the Drosophila melanogaster and Drosophila sechellia lineages, respectively. Intron selection pressures do not appear sufficient to explain all these results as the magnitude of the difference in synonymous and intron evolution is dependent on recombination environment and chromosomal location in a direction supporting the hypothesis of selectively driven synonymous fixations. This comparison identifies 101 loci with an apparent switch in codon preference between D. melanogaster and D. sechellia, a pattern previously only observed at the Notch locus.
    Genome Biology and Evolution 05/2009; 1:67-74. DOI:10.1093/gbe/evp008 · 4.23 Impact Factor
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