Differential Retention of Pfam Domains Contributes to Long-term Evolutionary Trends.

Protein domains that emerged more recently in evolution have a higher structural disorder and greater clustering of hydrophobic residues along the primary sequence. It is hard to explain how selection acting via descent with modification could act so slowly as not to saturate over the extraordinarily long timescales over which these trends persist. Here, we hypothesize that the trends were created by a higher level of selection that differentially affects the retention probabilities of protein domains with different properties. This hypothesis predicts that loss rates should depend on disorder and clustering trait values. To test this, we inferred loss rates via maximum likelihood for animal Pfam domains, after first performing a set of stringent quality control methods to reduce annotation errors. Intermediate trait values, matching those of ancient domains, are associated with the lowest loss rates, making our results difficult to explain with reference to previously described homology detection biases. Simulations confirm that effect sizes are of the right magnitude to produce the observed long-term trends. Our results support the hypothesis that differential domain loss slowly weeds out those protein domains that have nonoptimal levels of disorder and clustering. The same preferences also shape the differential diversification of Pfam domains, thereby further impacting proteome composition.

Universal and taxon-specific trends in protein sequences as a function of age.

Extant protein-coding sequences span a huge range of ages, from those that emerged only recently to those present in the last universal common ancestor. Because evolution has had less time to act on young sequences, there might be 'phylostratigraphy' trends in any properties that evolve slowly with age. A long-term reduction in hydrophobicity and hydrophobic clustering was found in previous, taxonomically restricted studies. Here we perform integrated phylostratigraphy across 435 fully sequenced species, using sensitive HMM methods to detect protein domain homology. We find that the reduction in hydrophobic clustering is universal across lineages. However, only young animal domains have a tendency to have higher structural disorder. Among ancient domains, trends in amino acid composition reflect the order of recruitment into the genetic code, suggesting that the composition of the contemporary descendants of ancient sequences reflects amino acid availability during the earliest stages of life, when these sequences first emerged.

High Transcriptional Error Rates Vary as a Function of Gene Expression Level.

Errors in gene transcription can be costly, and organisms have evolved to prevent their occurrence or mitigate their costs. The simplest interpretation of the drift barrier hypothesis suggests that species with larger population sizes would have lower transcriptional error rates. However, Escherichia coli seems to have a higher transcriptional error rate than species with lower effective population sizes, for example Saccharomyces cerevisiae. This could be explained if selection in E. coli were strong enough to maintain adaptations that mitigate the consequences of transcriptional errors through robustness, on a gene by gene basis, obviating the need for low transcriptional error rates and associated costs of global proofreading. Here, we note that if selection is powerful enough to evolve local robustness, selection should also be powerful enough to locally reduce error rates. We therefore predict that transcriptional error rates will be lower in highly abundant proteins on which selection is strongest. However, we only expect this result when error rates are high enough to significantly impact fitness. As expected, we find such a relationship between expression and transcriptional error rate for non-C→U errors in E. coli (especially G→A), but not in S. cerevisiae. We do not find this pattern for C→U changes in E. coli, presumably because most deamination events occurred during sample preparation, but do for C→U changes in S. cerevisiae, supporting the interpretation that C→U error rates estimated with an improved protocol, and which occur at rates comparable with E. coli non-C→U errors, are biological.

Biomarkers for Aging Identified in Cross-sectional Studies Tend to Be Non-causative.

Biomarkers are important tools for diagnosis, prognosis, and identification of the causal factors of physiological conditions. Biomarkers are typically identified by correlating biological measurements with the status of a condition in a sample of subjects. Cross-sectional studies sample subjects at a single timepoint, whereas longitudinal studies follow a cohort through time. Identifying biomarkers of aging is subject to unique challenges. Individuals who age faster have intrinsically higher mortality rates and so are preferentially lost over time, in a phenomenon known as cohort selection. In this article, we use simulations to show that cohort selection biases cross-sectional analysis away from identifying causal loci of aging, to the point where cross-sectional studies are less likely to identify loci that cause aging than if loci had been chosen at random. We go on to show this bias can be corrected by incorporating correlates of mortality identified from longitudinal studies, allowing cross-sectional studies to effectively identify the causal factors of aging.

Coevolution between Mutualists and Parasites in Symbiotic Communities May Lead to the Evolution of Lower Virulence.

Most eukaryotes harbor a diverse community of parasitic, mutualistic, and commensal microbial symbionts. Although the diversity of these microbial symbiotic communities has recently drawn considerable attention, theory regarding the evolution of interactions among symbionts and with the host is still in its nascent stages. Here we evaluate the role of interactions among coinfecting symbionts in the evolution of symbiont virulence toward the host. To do so, we place the virulence-transmission trade-off into a community context and model the evolution of symbiont trophic modes along the continuum from parasitism (virulence) to mutualism (negative virulence). We establish a framework for studying multiple infections of a host by the same symbiont species and coinfection by multiple species, using a concept of shared costs, wherein the negative consequences of virulence (or harm) toward the host are shared among symbionts. Our results show that mutualism can be maintained under infection by multiple symbionts when shared costs are sufficiently low, while greater virulence and parasitism toward the host are more likely when shared costs are high. Last, for coinfection by more than one species, we show that if the presence of a mutualist ameliorates some of the costs of pathogen virulence, then the symbiotic community may more often evolve to a more commensal state and maintain mutualisms.