The statistical methods applied to the analysis of genomic data do not account for uncertainty in the sequence alignment. Indeed, the alignment is treated as an observation, and all of the subsequent inferences depend on the alignment being correct. This may not have been too problematic for many phylogenetic studies, in which the gene is carefully chosen for, among other things, ease of alignment. However, in a comparative genomics study, the same statistical methods are applied repeatedly on thousands of genes, many of which will be difficult to align. Using genomic data from seven yeast species, we show that uncertainty in the alignment can lead to several problems, including different alignment methods resulting in different conclusions.

Study of the recently formed neo-Y chromosome of Drosophila miranda demonstrate that degeneration of a recently formed Y-chromosome can proceed very rapidly.

The detection of selection, both positive and negative, acting on a DNA sequence or class of nucleotide sites requires comparison with a reference sequence that is unaffected by selection. In Drosophila, recent findings of widespread selective constraint, as well as adaptive evolution, in both coding and noncoding regions highlight the difficulties in choosing such a reference sequence. Here, we investigate the utility of short intron sequences as a reference for the detection of selection. For a set of 119 Drosophila melanogaster genes containing 195 short introns (

The prevalence of natural selection relative to genetic drift is of central interest in evolutionary biology. Depending on the distribution of fitness effects of new mutations, the importance of these evolutionary forces may differ in species with different effective population sizes. Here, we survey population genetic variation at 105 orthologous X-linked protein coding regions in Drosophila melanogaster and its sister species D. simulans, two closely related species with distinct demographic histories. We observe significantly higher levels of polymorphism and evidence for stronger selection on codon usage bias in D. simulans, consistent with a larger historical effective population size on average for this species. Despite these differences, we estimate that <10% of newly arising nonsynonymous mutations have deleterious fitness effects in the nearly neutral range (i.e., −10 < Nes < 0) in both species. The inferred distributions of fitness effects and demographic models translate into surprisingly high estimates of the fraction of “adaptive” protein divergence in both species (∼85–90%). Despite evidence for different demographic histories, differences in population size have apparently played little role in the dynamics of protein evolution in these two species, and estimates of the adaptive fraction (α) of protein divergence in both species remain high even if we account for recent 10-fold growth. Furthermore, although several recent studies have noted strong signatures of recurrent adaptive protein evolution at genes involved in immunity, reproduction, sexual conflict, and intragenomic conflict, our finding of high levels of adaptive protein divergence at randomly chosen proteins (with respect to function) suggests that many other factors likely contribute to the adaptive protein divergence signature in Drosophila.