Determinants of mutation load in birds
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Abstract
Many mutations have detrimental effects. The mutation load in a population depends on the efficacy of purifying selection in removing deleterious genetic variation. Here, we estimated the proportion of deleterious mutations segregating in 24 population samples of 19 bird species. Exploiting the conserved avian karyotype with high variation in recombination rate and GC content, we quantified the joint effects of effective population size (Ne), recombination (r) and GC-biased gene-conversion (gBGC). In agreement with the nearly-neutral theory of molecular evolution, mutation load was substantially higher in populations with small Ne. Purging efficacy increased with recombination rate resulting in more than a two-fold difference of genetic load between large and small chromosomes. GC-biased mutations contributed about one third to the pool of deleterious mutations. Their expected accumulation in regions of high recombination was offset by purging efficacy in large, but not small populations. This study provides insight into how the interaction of evolutionary processes shapes mutation load. It suggests that genetic risk factors in small populations are fueled by gBGC and cluster in regions of low recombination.
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ρ / π = 4Ner / 4Neµ = r / µ.
This way of backing out recombination rate from Ner makes some strict assumptions, particularly that pi reflect mutation-drift equilibrium, and that mu is invariant across the genome. This is unlikely to be true in most datasets. It would be very helpful if more region specific comparisons could be made to pedigree based estimates to evaluate how well this approximation works in this dataset.
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We fitted a mixed effect model including all three parameters and a choice of meaningful interactions as fixed effects using the lmer function of the R package lme4
Again I think the influence of phylogenetic signal is important to consider here. A phylogenetically corrected regression (e.g. phylogenetic generalized least squares) would take into account the non-independence of species observations and provide a more accurate view of the data.
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Chromosome-level recombination rates were high across all comparisons (median R2=0.668, Supplementary Figure 3)
It would be nice to get an idea of how stable this porting over of the estimated recombination map is across phylogenetic distance. There is considerable variation in the correlation among species pairs which would be good to understand. Also would be valuable to show the reader how the phylogenetic distance of these comparisons relates to the distances used for comparisons of the main analysis.
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Theoretical considerations on mutation load.
The message of this figure get's a little muddled. One would expect that as as Ne increases, that the proportion of mutations experiencing a larger (more negative) Nes would grow (as in the case of increasing r) but the opposite is shown. Unless the figure implies that fewer segregating mutations will have large Nes? But then this conflicts with the sequence for recombination.
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