bioRxiv Science⌕ Search

bioRxiv · 10.1101/2024.10.15.618444

Genealogies under purifying selection

Abstract

Selection against deleterious mutations, called purifying selection, plays a central role in evolution and acts in all populations. It is known that the genetic patterns observed in genomic regions undergoing purifying selection differ from those resulting from neutral evolution. However, a comprehensive understanding of the underlying mechanisms shaping those patterns is still lacking. In the present work, we use simulations combined with a genealogical approach to identify the effect of purifying selection on the ancestry and thus on the genetic diversity. Our analysis relies on the postulate that the genealogy belongs to the universality class of Beta-coalescents. Under this assumption, we derive statistics measuring the distortion of the genealogy. This approach allows us to consider a wide range of regimes (i.e. arbitrary selection and mutation strengths) and uncover a rich phase diagram. We find that, for strong selection, the limiting genealogy is given by Kingmans coalescent on a polynomial timescale. As selection gets weaker, Mullers ratchet starts operating, setting off the emergence of multiple mergers in the genealogical structures. Our results show that while multiple-merger coalescents are often interpreted as the signature of selective sweeps in rapidly adapting populations, these structures can also appear in the context of Mullers ratchet.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Khudiakova, K. A., Boenkost, F., Tourniaire, J.. 2024-10-18. Genealogies under purifying selection. https://doi.org/10.1101/2024.10.15.618444

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

RELAX does not reproduce its own estimates at default settings, and its output does not show it

Selection-intensity estimates from RELAX are reported as a point value of K with a likelihood-ratio P. We report that, at default settings and on data of ordinary size, the program does not reproduce its own fits. Of 27 enzyme entries refitted under two optimiser configurations, none reproduced its log-likelihood to within 0.01 units; the median change was 103 units, the largest over 3,400, and four verdicts reversed. Eighty null orthologues reproduced none. A byte-identical command returned a distinct likelihood on every repetition, single-threaded, across three releases, and on alignments simulated under the fitted model, where 3.3 per cent of replicates reproduced. The documented random-number seed never reaches the generator when assigned on the command line, yet reads back as the value supplied. PAML localises the cause: its two-ratio model, without site classes, reproduced its log-likelihood for all 288 genes; its site-class models agreed for 27 to 67 per cent. The instability follows the mixture over sites, not the program. The output does not show it: 46 of 410 fits ended with a negative likelihood-ratio statistic, impossible under convergence, and 123 of 410 report a K re-estimated under a domain restriction rather than the unconstrained maximum. Of 234 published studies using RELAX, none reported a seed. Seeding while holding the thread count at one reproduced sixty of sixty runs on twenty genes under two releases; the seed alone reproduced none of five, and no documentation states the second condition. We recommend that fits be repeated and their dispersion published.

evolutionary biology↗

Sequential accumulation of adaptive alleles forms an inversion supergene in deer mice

Supergenes are clusters of co-inherited loci that affect multiple or complex phenotypes. Despite the growing number of chromosomal inversions identified as supergenes in natural populations, their molecular basis and evolutionary history often remain obscure. Here, we identified two candidate genes, Slc45a2 and Npr3, within a 41-Mb inversion supergene in the deer mouse (Peromyscus maniculatus) that respectively drive darker coats and longer tails - two traits associated with forest adaptation. Mice homozygous for the inversion (inv/inv) exhibit elevated Slc45a2 expression in melanocytes relative to the congenic standard genotype (std/std), disrupting pheomelanin production. In parallel, downregulation of Npr3 in inv/inv mouse growth plates prolongs postnatal growth of caudal vertebrae, resulting in tail elongation. Population-level analyses further implicate that this supergene arose through the subsequent accumulation of the Npr3 allele within the inversion, rather than by capturing all beneficial mutations at its origin.

evolutionary biology↗

Toxin structure shapes palatability in a chemically defended butterfly

The toxicity of chemical defences is well studied, but the potential contribution of compound structure to predator deterrence remains largely unexplored. Whether predation acts more strongly on toxicity or unpalatability remains largely untested, partly because few systems allow toxin structure to vary independently of quantity. Heliconius sara larvae provide such a system: those reared on Passiflora auriculata sequester cyclopentenyl cyanogenic glucosides (CGs), while those reared on P. biflora biosynthesise comparable quantities of aliphatic CGs. Using two invertebrate predators, Camponotus floridanus ants and Hierodula membranacea mantids, we tested whether this structural difference affects palatability independent of toxicity. Mantids rejected larvae with cyclopentenyl CGs more often than larvae with aliphatic CGs, despite no detectable difference in total CG content. This pattern was mirrored in extract-based assays with ants, independently of cyanide release: extracts with cyclopentenyl CGs remained deterrent, while extracts with aliphatic CGs did not differ in deterrence from water. Live larvae, by contrast, elicited similar responses from ants regardless of CG structure. These results show that variation in toxin structure can strongly affect palatability, with some compounds conferring greater protection than others. This demonstrates the importance of chemical structural diversity in the evolution of chemical defences.

evolutionary biology↗