Positive and negative selection on noncoding DNA in Drosophila simulans - PubMed (original) (raw)

Positive and negative selection on noncoding DNA in Drosophila simulans

Penelope R Haddrill et al. Mol Biol Evol. 2008 Sep.

Abstract

There is now a wealth of evidence that some of the most important regions of the genome are found outside those that encode proteins, and noncoding regions of the genome have been shown to be subject to substantial levels of selective constraint, particularly in Drosophila. Recent work has suggested that these regions may also have been subject to the action of positive selection, with large fractions of noncoding divergence having been driven to fixation by adaptive evolution. However, this work has focused on Drosophila melanogaster, which is thought to have experienced a reduction in effective population size (N(e)), and thus a reduction in the efficacy of selection, compared with its closest relative Drosophila simulans. Here, we examine patterns of evolution at several classes of noncoding DNA in D. simulans and find that all noncoding DNA is subject to the action of negative selection, indicated by reduced levels of polymorphism and divergence and a skew in the frequency spectrum toward rare variants. We find that the signature of negative selection on noncoding DNA and nonsynonymous sites is obscured to some extent by purifying selection acting on preferred to unpreferred synonymous codon mutations. We investigate the extent to which divergence in noncoding DNA is inferred to be the product of positive selection and to what extent these inferences depend on selection on synonymous sites and demography. Based on patterns of polymorphism and divergence for different classes of synonymous substitution, we find the divergence excess inferred in noncoding DNA and nonsynonymous sites in the D. simulans lineage difficult to reconcile with demographic explanations.

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Figures

F<sc>IG</sc>. 1.—

FIG. 1.—

Mean Tajima's D values for coding and noncoding DNA in Drosophila simulans, using the Drosophila melanogaster outgroup. The dashed line indicates the mean expected value of Tajima's D under a model of neutral evolution for a sample of 20 individuals with similar levels of variability to those found here (no recombination, see table 1 of Tajima [1989]). Error bars indicate 2 standard errors. Syn: synonymous sites, NonSyn: nonsynonymous sites, and NonCod: pooled noncoding sites.

F<sc>IG</sc>. 2.—

FIG. 2.—

The distribution of frequency classes of polymorphisms for different types of synonymous site changes, nonsynonymous site changes, and noncoding DNA changes. Within synonymous site changes, P → P/U → U includes preferred to preferred and unpreferred to unpreferred changes, P → U are preferred to unpreferred changes, and U → P are unpreferred to preferred changes. “Neutral” indicates the neutral expectation. The low-frequency class includes polymorphisms at a frequency of 1–2/20, the intermediate frequency class 3–17/20, and the high-frequency class 18–19/20. The numbers above each type of synonymous site change indicate the percentage of the total synonymous polymorphisms of each type.

F<sc>IG</sc>. 3.—

FIG. 3.—

Estimates of the fraction of adaptively driven nucleotide substitutions (α) in coding and noncoding DNA (a) between Drosophila simulans and Drosophila melanogaster and (b) inferred along the D. simulans lineage using a reconstructed ancestor. NonSyn: nonsynonymous sites. For each class of sequence, 4 estimates are presented based on the subset of polymorphisms that were included in the analysis: P_all, all polymorphisms included; P_freq > 0.05, polymorphisms at a frequency of greater than 5% (singletons) included; P_freq > 0.1, polymorphisms at a frequency of greater than 10% (doubletons) included; and P_freq > 0.15, polymorphisms at a frequency of greater than 15% (tripletons) included. Error bars indicate 90% CIs.

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