Genomic Heterogeneity of Background Substitutional Patterns in Drosophila melanogaster

Abstract

Mutation is the underlying force that provides the variation upon which evolutionary forces can act. It is important to understand how mutation rates vary within genomes and how the probabilities of fixation of new mutations vary as well. If substitutional processes across the genome are heterogeneous, then examining patterns of coding sequence evolution without taking these underlying variations into account may be misleading. Here we present the first rigorous test of substitution rate heterogeneity in the Drosophila melanogaster genome using almost 1500 nonfunctional fragments of the transposable element DNAREP1_DM. Not only do our analyses suggest that substitutional patterns in heterochromatic and euchromatic sequences are different, but also they provide support in favor of a recombination-associated substitutional bias toward G and C in this species. The magnitude of this bias is entirely sufficient to explain recombination-associated patterns of codon usage on the autosomes of the D. melanogaster genome. We also document a bias toward lower GC content in the pattern of small insertions and deletions (indels). In addition, the GC content of noncoding DNA in Drosophila is higher than would be predicted on the basis of the pattern of nucleotide substitutions and small indels. However, we argue that the fast turnover of noncoding sequences in Drosophila makes it difficult to assess the importance of the GC biases in nucleotide substitutions and small indels in shaping the base composition of noncoding sequences.M UTATION is the substrate of evolution; it creates by selective forces specific to their functional capacity. In the variation upon which evolutionary forces will some cases, such selective effects are well known, such as ultimately act. With every novel mutation there is an those related to maintenance of the integrity of proteinassociated probability of fixation, which may be affected coding sequences, but many other, possibly more subtle, by neutral forces, such as random genetic drift or biased patterns are likely yet to be discovered. gene conversion, or selective forces. Both mutation ratesIn this context, the study of the background patterns and fixation probabilities of new mutations may vary of substitution not only is interesting in its own right, but across the genome, which may play a role in generating also should help us rigorously define null hypotheses patterns of extant sequence variation. One of the goals against which we can compare patterns of substitution of genomic biology is to understand how heterogeneity found in functional sequences such as genes. This, in in evolutionary forces such as mutation, drift, biased gene turn, should help us identify selective forces that act conversion, and selection can actively shape genome sewithin genes and thereby understand which genic feaquences and structure.tures are of functional significance. The evolution of both functional and nonfunctional seIn this genomic age, the need for careful quantificaquences might be modulated by an...

GC-Biased Segregation of Noncoding Polymorphisms in Drosophila

“…The biased-transmission hypothesis predicts the strong correlation between asymmetric polymorphism and GC-content-loci undergoing a GC-biased segregation of polymorphisms tend to be GC richer. Consistently, Singh et al (2005) reported a significant correlation between recombination rate and GC-substitution bias of a genomewide repeated element in D. melanogaster. The GC-biased-transmission model is also consistent with the stationary evolution of GC content of noncoding sequences in D. melanogaster and D. simulans reported by Kern and Begun (2005).…”

No effect of recombination on the efficacy of natural selection in primates

“…Early investigations of variation in the efficacy of selection focused on the strength of codon bias within a single genome (Kliman and Hey 1993;Hey and Kliman 2002), finding weaker codon bias in regions of low recombination. While consistent with a lower efficacy of selection, the interpretation of these observations is not clear-cut (Marais et al 2003;Singh et al 2005).…”

The Hill–Robertson effect: evolutionary consequences of weak selection and linkage in finite populations

“…Nevertheless, a GC-biased gene conversion model (Nagylaki, 1983) predicts that noncoding regions would show (1) a continuous increase in G þ C content with recombination and (2) a reduction in rates of evolution in genomic regions with high recombination and G þ C content. In D. melanogaster, the correlation between recombination rate and either codon bias or noncoding G þ C content is not observed in regions with very high recombination rates (Kliman and Hey, 2003) and substitution rates at noncoding regions are not reduced in regions with high recombination (Singh et al, 2005). Altogether, these observations are more consistent with a relaxation of long-range HR effects in regions of high recombination coupled with a recent increase in mutational biases toward AT (Kern and Begun, 2005;Akashi et al, 2006).…”