Biology subjects

Nelson, P. G.

Publications and source records attributed to Nelson, P. G..

6 recordsLinked to original sources

bioRxiv2020

The protein domains of vertebrate species in whichselection is more effective have greater intrinsicstructural disorder

The effectiveness of selection varies among species. It is often estimated by means of an "effective population size" based on neutral polymorphism, but this is confounded in complex ways with demography. The strength of codon bias more directly pertains to how well adaptation at many sites can be maintained in the face of deleterious mutations, but past metrics that compare codon bias across species are confounded by among-species variation in %GC content and/or amino acid composition. Here we propose a new Codon Adaptation Index of Species (CAIS) that corrects for both confounders. Unlike previous metrics, CAIS yields the expected relationship with adult vertebrate body mass. As an example of the use of CAIS, we ask whether protein domains evolve lower intrinsic structural disorder (ISD) when present in more exquisitely adapted species, as expected given that ISD is higher in eukaryotic proteomes than prokaryotic proteomes. Using phylogenetically corrected linear models, we find, contrary to expectations, that the ISD of a given protein domain evolves to be higher when in well-adapted species. This effect is stronger in young protein domains but is also present in ancient domains.

evolutionary biology↗

bioRxiv2020

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 in particular lineages, 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. Indeed, a long-term reduction in hydrophobicity and in hydrophobic clustering has been found in previous, taxonomically restricted studies. Here we perform integrated phylostratigraphy across 435 fully sequenced and dated eukaryotic species, using sensitive HMM methods to detect homology of protein domains (which may vary in age within the same gene), and applying a variety of quality filters. We find that the reduction in hydrophobic clustering is universal across diverse lineages, showing limited sign of saturation. But the tendency for young domains to have higher protein structural disorder, driven primarily by more hydrophilic amino acids, is found only among young animal domains, and not young plant domains, nor ancient domains predating the existence of the last eukaryotic common ancestor. Among ancient domains, trends in amino acid composition reflect the order of recruitment into the genetic code, suggesting that events during the earliest stages of life on earth continue to have an impact on the composition of ancient sequences.

evolutionary biology↗

bioRxiv2019

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, while 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 paper, 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.

bioinformatics↗

bioRxiv2019

Transcriptional Error Rates Vary by Gene Expression Level in E. coli but not S. cerevisiae

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, e.g. 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 CU errors in E. coli (especially GA), but not in S. cerevisiae. We do not find this pattern for CU changes in E. coli, presumably because most deamination events occurred during sample preparation, but do for CU changes in S. cerevisiae, supporting the interpretation that CU error rates estimated with an improved protocol, and which occur at rates comparable to E. coli non CU errors, are biological.

evolutionary biology↗

bioRxiv2018

Defensive symbiosis and the evolution of virulence

Although environments rife with enemies should cause selection for defensive traits, such enemy-rich environments should also select for greater virulence in co-occurring symbionts, yet many defensive symbionts cause little to no damage while protecting their hosts from enemies. Thus, co-infection of a defensive symbiont and a parasite is predicted to select both for increased virulence in co-infecting symbionts and for increased defense in the protective symbiont. Why then do we observe defensive mutualists that protect hosts while causing little damage? To address this question, we build a symbiont-centered model that incorporates the evolution of two independent traits: defense and virulence. Virulence is modeled as a continuous trait spanning mutualism (negative virulence) and parasitism (virulence) and thus accounts for the entire range of direct effects that symbionts have on host mortality. Defense is modeled as a continuous trait that ameliorates the costs to the host associated with co-infection with a deleterious parasite. We obtain the counterintuitive result that the evolution of increased defense in one symbiont largely leads to the evolution of lower virulence in both symbionts and may even facilitate pathogens evolving to mutualism. However, results are context-dependent and when defensive traits are costly, the evolution of greater defense may also lead to higher virulence.

evolutionary biology↗

bioRxiv2017

Evolutionary capacitance emerges spontaneously during adaptation to environmental changes

All biological populations are to a greater or lesser degree evolvable, but the forces that shape evolvability, especially the evolution of evolvability as an adaptive response to a changing environment, have been a source of controversy. One source of enhanced evolvability is the benign status of \"cryptic sequences\" typically expressed at low levels due to molecular errors, but with the potential to be expressed more fully following mutational co-option. A genome enriched for benign cryptic sequences has a more benign mutational neighborhood, via the possibility of co-option, and thus enhanced evolvability. Whether selection for evolvability itself can be the cause of a more benign mutational neighborhood remains an open question. Here, we show that environmental change can cause the evolution of increased evolvability, despite our use of a strong-selection weak mutation regime that precludes, by design, the adaptive evolution of evolvability. Instead, enhanced evolvability arises as a byproduct of environmental change via a novel mechanism that we call \"emergent evolutionary capacitance\". When the environment changes, increased molecular error rates evolve as a strategy to rapidly change phenotypes, with the side effect of purging deleterious cryptic sequences and enhancing the mutational neighborhood for future adaptation. The behavior is strikingly similar to that seen in a model system for capacitance, the yeast prion [PSI+].

evolutionary biology↗