Inferring Adaptive Codon Preference to Understand Sources of Selection Shaping Codon Usage Bias.

Alternative synonymous codons are often used at unequal frequencies. Classically, studies of such codon usage bias (CUB) attempted to separate the impact of neutral from selective forces by assuming that deviations from a predicted neutral equilibrium capture selection. However, GC-biased gene conversion (gBGC) can also cause deviation from a neutral null. Alternatively, selection has been inferred from CUB in highly expressed genes, but the accuracy of this approach has not been extensively tested, and gBGC can interfere with such extrapolations (e.g., if expression and gene conversion rates covary). It is therefore critical to examine deviations from a mutational null in a species with no gBGC. To achieve this goal, we implement such an analysis in the highly AT rich genome of Dictyostelium discoideum, where we find no evidence of gBGC. We infer neutral CUB under mutational equilibrium to quantify "adaptive codon preference," a nontautologous genome wide quantitative measure of the relative selection strength driving CUB. We observe signatures of purifying selection consistent with selection favoring adaptive codon preference. Preferred codons are not GC rich, underscoring the independence from gBGC. Expression-associated "preference" largely matches adaptive codon preference but does not wholly capture the influence of selection shaping patterns across all genes, suggesting selective constraints associated specifically with high expression. We observe patterns consistent with effects on mRNA translation and stability shaping adaptive codon preference. Thus, our approach to quantifying adaptive codon preference provides a framework for inferring the sources of selection that shape CUB across different contexts within the genome.

Evolutionary coincidence of adaptive changes in exuperantia and the emergence of bicoid in Cyclorrhapha (Diptera).

The great radiation in the infraorder Cyclorrhapha involved several morphological and molecular changes, including important changes in anterior egg development. During Drosophila oogenesis, exuperantia (exu) is critical for localizing bicoid (bcd) messenger RNA (mRNA) to the anterior region of the oocyte. Because it is phylogenetically older than bcd, which is exclusive to Cyclorrhapha, we hypothesize that exu has undergone adaptive changes to enable this new function. Although exu has been well studied in Drosophila, there is no functional or transcriptional information about it in any other Diptera. Here, we investigate exu in the South American fruit fly Anastrepha fraterculus, a Cyclorrhapha of great agricultural importance that have lost bcd, aiming to understand the evolution of exu in this infraorder. We assessed its pattern of gene expression in A. fraterculus by analyzing transcriptomes from cephalic and reproductive tissues. A combination of next-generation data with classical sequencing procedures enabled identification of the structure of exu and its alternative transcripts in this species. In addition to the sex-specific isoforms described for Drosophila, we found that not only exu is expressed in heads, but this is mediated by two transcripts with a specific 5'UTR exon-likely a result from usage of a third promoter. Furthermore, we tested the hypothesis that exu is evolving under positive selection in Cyclorrhapha after divergence from lower Diptera. We found evidence of positive selection at two important exu domains, EXO-like and SAM-like, both involved with mRNA binding during bcd mRNA localization in Drosophila, which could reflect its cooptation for the new function of bcd mRNA localization in Cyclorrhapha.

Conditional expression explains molecular evolution of social genes in a microbe.

Conflict is thought to play a critical role in the evolution of social interactions by promoting diversity or driving accelerated evolution. However, despite our sophisticated understanding of how conflict shapes social traits, we have limited knowledge of how it impacts molecular evolution across the underlying social genes. Here we address this problem by analyzing the genome-wide impact of social interactions using genome sequences from 67 Dictyostelium discoideum strains. We find that social genes tend to exhibit enhanced polymorphism and accelerated evolution. However, these patterns are not consistent with conflict driven processes, but instead reflect relaxed purifying selection. This pattern is most likely explained by the conditional nature of social interactions, whereby selection on genes expressed only in social interactions is diluted by generations of inactivity. This dilution of selection by inactivity enhances the role of drift, leading to increased polymorphism and accelerated evolution, which we call the Red King process.