A gene-based model of fitness and its implications for genetic variation DOI Creative Commons
Parul Johri, Brian Charlesworth

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 14, 2024

A widely used model of the effects mutations on fitness (the "sites" model) assumes that heterozygous recessive or partially deleterious at different sites in a gene complement each other, similarly to genes. However, general lack complementation between major effect allelic suggests an alternative possibility, which we term "gene" model. This pair trans behave effectively as homozygotes, so fitnesses heterozygotes are lower than those cis heterozygotes. We examine properties two models, using both analytical and simulation methods. show predicts positive linkage disequilibrium (LD) variants within coding sequence, under conditions when zero slightly negative LD. also focussing rare examining patterns LD, especially with Lewontin's D ' measure, is likely produce misleading results respect inferences concerning causes sign Synergistic epistasis pairs was modeled; it less LD The theoretical discussed relation natural populations several species.

Language: Английский

Population size rescaling significantly biases outcomes of forward-in-time population genetic simulations DOI
Amjad Dabi, Daniel R. Schrider

Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

Simulations are an essential tool in all areas of population genetic research, used tasks such as the validation theoretical analysis and study complex evolutionary models. Forward-in-time simulations especially flexible, allowing for various types natural selection, architectures, non-Wright-Fisher dynamics. However, their intense computational requirements can be prohibitive to simulating large populations genomes. A popular method alleviate this burden is scale down size by some scaling factor while up mutation rate, selection coefficients, recombination rate same factor. rescaling approach may cases bias simulation results. To investigate manner degree which impacts outcomes, we carried out with different demographic histories distributions fitness effects using several values factor, Ǫ, compared deviation key outcomes (fixation times, allele frequencies, linkage disequilibrium, fraction mutations that fix during simulation) between scaled unscaled simulations. Our results indicate introduces substantial biases each these measured even at small Ʈ. Moreover, nature depends on model being examined. While increasing tends increase observed biases, relationship not always straightforward, thus it difficult know impact a priori. appears most models, only number replicates was needed accurately quantify produced given In summary, forward-in-time necessary many cases, researchers should aware procedure's consider investigating its magnitude smaller desired model(s) before selecting appropriate value

Language: Английский

Citations

4
Accessible, realistic genome simulation with selection usingstdpopsim DOI Creative Commons
Graham Gower, Nathaniel S. Pope, Murillo F. Rodrigues

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 23, 2025

Selection is a fundamental evolutionary force that shapes patterns of genetic variation across species. However, simulations incorporating realistic selection along heterogeneous genomes in complex demographic histories are challenging, limiting our ability to benchmark statistical methods aimed at detecting and explore theoretical predictions. stdpopsim community-maintained simulation library already provides an extensive catalog species-specific population models. Here we present major extension the framework enables various modes selection, including background selective sweeps, arbitrary distributions fitness effects (DFE) acting on annotated subsets genome (for instance, exons). This maintains 's core principles reproducibility accessibility while adding support for genomic annotations published DFE estimates. We demonstrate utility this by benchmarking inference, estimation, sweep detection several species scenarios. Our results robustness inference linked sites, reveal sensitivity DFE-inference model assumptions, show how features, like recombination rate functional sequence density, influence power detect sweeps. powerful new resource genetics community interplay between other forces reproducible, low-barrier framework.

Language: Английский

Citations

0
A gene-based model of fitness and its implications for genetic variation DOI Creative Commons
Parul Johri, Brian Charlesworth

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 14, 2024

A widely used model of the effects mutations on fitness (the "sites" model) assumes that heterozygous recessive or partially deleterious at different sites in a gene complement each other, similarly to genes. However, general lack complementation between major effect allelic suggests an alternative possibility, which we term "gene" model. This pair trans behave effectively as homozygotes, so fitnesses heterozygotes are lower than those cis heterozygotes. We examine properties two models, using both analytical and simulation methods. show predicts positive linkage disequilibrium (LD) variants within coding sequence, under conditions when zero slightly negative LD. also focussing rare examining patterns LD, especially with Lewontin's D ' measure, is likely produce misleading results respect inferences concerning causes sign Synergistic epistasis pairs was modeled; it less LD The theoretical discussed relation natural populations several species.

Language: Английский

Citations

3