Academic journal article Genetics

Genomic Heterogeneity of Background Substitutional Patterns in Drosophila Melanogaster

Academic journal article Genetics

Genomic Heterogeneity of Background Substitutional Patterns in Drosophila Melanogaster

Article excerpt

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.

MUTATION is the substrate of evolution; it creates the variation upon which evolutionary forces will ultimately act. With every novel mutation there is an associated probability of fixation, which may be affected by neutral forces, such as random genetic drift or biased gene conversion, or selective forces. Both mutation rates and fixation probabilities of new mutations may vary across the genome, which may play a role in generating patterns of extant sequence variation. One of the goals of genomic biology is to understand how heterogeneity in evolutionary forces such as mutation, drift, biased gene conversion, and selection can actively shape genome sequences and structure.

The evolution of both functional and nonfunctional sequences might be modulated by any or all of these forces, though perhaps to different extents. It is likely that mutational patterns and rates are going to be comparable in both functional and nonfunctional regions of the genome. It is also probable that certain fixation biases, for example, due to biased gene conversion or selection at the level of global GC content, will affect functional and nonfunctional sequences in a similar way. However, in addition to these background patterns of substitutions, functional sequences are likely to have unique fixation biases driven by selective forces specific to their functional capacity. In some cases, such selective effects are well known, such as those related to maintenance of the integrity of proteincoding sequences, but many other, possibly more subtle, patterns are likely yet to be discovered.

In this context, the study of the background patterns of substitution not only is interesting in its own right, but also should help us rigorously define null hypotheses against which we can compare patterns of substitution found in functional sequences such as genes. This, in turn, should help us identify selective forces that act within genes and thereby understand which genie features are of functional significance.

In this genomic age, the need for careful quantification of background substitutional patterns has become particularly acute. More and more studies compare patterns of evolution among genes scattered across the genome. Differences among these genes in nucleotide or protein evolution are often interpreted as indications of differences in gene function or in the strength of natural selection acting on functions encoded in genie sequences. …

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