Biology subjects

Matheson, J. D.

Publications and source records attributed to Matheson, J. D..

3 recordsLinked to original sources

bioRxiv2023

Human deleterious mutation rate implies high fitness variance, with declining mean fitness compensated by rarer beneficial mutations of larger effect

Each new human has an expected Ud = 2-10 new deleterious mutations. Using a novel approach to capture complex linkage disequilibria from high Ud using genome-wide simulations, we confirm that fitness decline due to the fixation of many slightly deleterious mutations can be compensated by rarer beneficial mutations of larger effect. The evolution of increased genome size and complexity have previously been attributed to a similarly asymmetric pattern of fixations, but we propose that the cause might be high Ud rather than the small population size posited as causal by drift barrier theory. High within-population variance in relative fitness is an inevitable consequence of high Ud[~]2-10 combined with inferred human deleterious effect sizes; two individuals will typically differ in fitness by 15-40%. The need to compensate for the deluge of deleterious mutations slows net adaptation (i.e. to the external environment) by [~]13%-55%. The rate of beneficial fixations is more sensitive to changes in the mutation rate than the rate of deleterious fixations is. As a surprising consequence of this, an increase (e.g. 10%) in overall mutation rate leads to faster adaptation; this puts to rest dysgenic fears about increasing mutation rates due to rising paternal age.

evolutionary biology↗

bioRxiv2022

Background selection theory overestimates effective population size for high mutation rates

Background selection describes the reduction in neutral diversity caused by selection against deleterious alleles at other loci. It is typically assumed that the purging of deleterious alleles affects linked neutral variants, and indeed simulations typically only treat a genomic window. However, background selection at unlinked loci also depresses neutral diversity. In agreement with previous analytical approximations, in our simulations of a human-like genome with a realistically high genome-wide deleterious mutation rate, the effects of unlinked background selection exceed those of linked background selection. Background selection reduces neutral genetic diversity by a factor that is independent of census population size. Outside of genic regions, the strength of background selection increases with the mean selection coefficient, contradicting the linked theory but in agreement with the unlinked theory. Neutral diversity within genic regions is fairly independent of the strength of selection. Deleterious genetic load among haploid individuals is underdispersed, indicating non-independent evolution of deleterious mutations. Empirical evidence for underdispersion was previously interpreted as evidence for global epistasis, but we recover it from a non-epistatic model. SIGNIFICANCEAs individuals bearing deleterious alleles are removed from a population, other alleles are removed with them, some that are tightly linked near the deleterious allele on a chromosome and some that arent linked at all. When the deleterious mutation rate is realistically high, unlinked pairs of loci are a more important influence on the removal of genetic variation. Simulations that assume independent evolution cannot capture removal just by using a lower "effective population size", because the probabilities of having deleterious alleles on different chromosomes are negatively correlated rather than independent.

evolutionary biology↗

bioRxiv2021

Haldane's cost of selection imposes a mild constraint on adaptation, with a high proportion of deaths in A. thaliana being selective

Haldanes Dilemma refers to the concern that the need for many "selective deaths" to complete a substitution (i.e. selective sweep) creates a speed limit to adaptation. However, discussion of this concern has been marked by confusion, especially with respect to the term "substitution load". Here we distinguish different historical lines of reasoning, and identify one, focused on finite reproductive excess and the proportion of deaths that are "selective" (i.e. causally contribute to adaptive allele frequency changes), that has not yet been fully addressed. We develop this into a more general theoretical model that can apply to populations with any life history, even those for which a generation or even an individual are not well defined. The actual speed of adaptive evolution is coupled to the proportion of deaths that are selective. The degree to which reproductive excess enables a high proportion of selective deaths depends on the details of when selection takes place relative to density regulation, and there is therefore no general expression for a speed limit. To make these concepts concrete, we estimate both reproductive excess, and the proportion of deaths that are selective, from a dataset measuring survival of 517 different genotypes of Arabidopsis thaliana grown in eight different environmental conditions. In this dataset, a much higher proportion of deaths contribute to adaptation, in all environmental conditions, than the 10% cap that was anticipated as substantially restricting adaptation during historical discussions of speed limits. LAY SUMMARYThe influential neutral theory of molecular evolution was predicated on theoretical arguments that adaptation is subject to a speed limit. We resolve confusions regarding historical speed limit arguments, which depend on differences in fitness, not variance (differences in fitness squared). We generalize the underlying concepts of selective deaths and reproductive excess to populations with any life cycle, even those for which an "individual" and hence generation and fitness, are poorly defined. We apply the revised theory to Arabidopsis data, demonstrating the potential for future related experiments.

evolutionary biology↗