Transcriptional Robustness Complements Nonsense-Mediated Decay in Humans

In eukaryotes, gene expression is a complex, multi-step process involving transcription, splicing, translation, and post-translational modifications. At each individual step, errors can occur that lead to nonfunctional and potentially toxic proteins. Therefore, eukaryotes have evolved a wide array of solutions to minimize the risk of error.This work was supported by NIH grant R01 GM088344 to COW. The funder had no role in the preparation of the article.Cellular and Molecular Biolog

Epistasis not needed to explain low dN/dS

An important question in molecular evolution is whether an amino acid that occurs at a given position makes an independent contribution to fitness, or whether its effect depends on the state of other loci in the organism's genome, a phenomenon known as epistasis. In a recent letter to Nature, Breen et al. (2012) argued that epistasis must be "pervasive throughout protein evolution" because the observed ratio between the per-site rates of non-synonymous and synonymous substitutions (dN/dS) is much lower than would be expected in the absence of epistasis. However, when calculating the expected dN/dS ratio in the absence of epistasis, Breen et al. assumed that all amino acids observed in a protein alignment at any particular position have equal fitness. Here, we relax this unrealistic assumption and show that any dN/dS value can in principle be achieved at a site, without epistasis. Furthermore, for all nuclear and chloroplast genes in the Breen et al. dataset, we show that the observed dN/dS values and the observed patterns of amino acid diversity at each site are jointly consistent with a non-epistatic model of protein evolution.Comment: This manuscript is in response to "Epistasis as the primary factor in molecular evolution" by Breen et al. Nature 490, 535-538 (2012

Adaptive Developmental Delay in Chagas Disease Vectors: An Evolutionary Ecology Approach

The developmental time of vector insects is important to their population dynamics, evolutionary biology, epidemiology of the diseases they transmit, and to their responses to global climatic change. In various triatomine species vectors of Chagas disease (Triatominae, Reduviidae), a delay in the molt of a small proportion of individuals has been observed, and from an evolutionary ecology approach, we propose the hypothesis that the developmental delay is an adaptation to environmental stochasticity through a spreading of risk (bet-hedging) diapause strategy. We confirmed, by means of a survey among specialists, the existence of the developmental delay in triatomines. Statistical descriptions of the developmental time of 11 species of triatomines showed some degree of bi-modality in nine of them. We predicted by means of an optimization model which genotype, coding for a given frequency of developmental diapause, is expected to evolve. We identified a series of parameters that can be measured in the field and in the laboratory to test the hypothesis of an optimal diapause frequency. We also discuss the importance of these findings for triatomines in terms of global climatic change and epidemiological consequences such as their resistance to insecticides

Bringing Molecules Back into Molecular Evolution

Much molecular-evolution research is concerned with sequence analysis. Yet these sequences represent real, three-dimensional molecules with complex structure and function. Here I highlight a growing trend in the field to incorporate molecular structure and function into computational molecular-evolution work. I consider three focus areas: reconstruction and analysis of past evolutionary events, such as phylogenetic inference or methods to infer selection pressures; development of toy models and simulations to identify fundamental principles of molecular evolution; and atom-level, highly realistic computational modeling of molecular structure and function aimed at making predictions about possible future evolutionary events