Biology subjects

Cavassim, M. I. A.

Publications and source records attributed to Cavassim, M. I. A..

8 recordsLinked to original sources

bioRxiv2025

Accessible, realistic genome simulation with selection using stdpopsim

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 selection and to explore theoretical predictions. stdpopsim is a community-maintained simulation library that already provides an extensive catalog of species-specific population genetic models. Here we present a major extension to the stdpopsim framework that enables simulation of various modes of selection, including background selection, selective sweeps, and arbitrary distributions of fitness effects (DFE) acting on annotated subsets of the genome (for instance, exons). This extension maintains stdpopsims core principles of reproducibility and accessibility while adding support for species-specific genomic annotations and published DFE estimates. We demonstrate the utility of this framework by comparing methods for demographic inference, DFE estimation, and selective sweep detection across several species and scenarios. Our results demonstrate the robustness of demographic inference methods to selection on linked sites, reveal the sensitivity of DFE-inference methods to model assumptions, and show how genomic features, like recombination rate and functional sequence density, influence power to detect selective sweeps. This extension to stdpopsim provides a powerful new resource for the population genetics community to explore the interplay between selection and other evolutionary forces in a reproducible, user-friendly framework.

evolutionary biology↗

bioRxiv2022

Expanding the stdpopsim species catalog, and lessons learned forrealistic genome simulations

Simulation is a key tool in population genetics for both methods development and empirical research, but producing simulations that recapitulate the main features of genomic data sets remains a major obstacle. Today, more realistic simulations are possible thanks to large increases in the quantity and quality of available genetic data, and to the sophistication of inference and simulation software. However, implementing these simulations still requires substantial time and specialized knowledge. These challenges are especially pronounced for simulating genomes for species that are not well-studied, since it is not always clear what information is required to produce simulations with a level of realism sufficient to confidently answer a given question. The community-developed framework stdpopsim seeks to lower this barrier by facilitating the simulation of complex population genetic models using up-to-date information. The initial version of stdpopsim focused on establishing this framework using six well-characterized model species (Adrion et al., 2020). Here, we report on major improvements made in the new release of stdpopsim (version 0.2), which includes a significant expansion of the species catalog and substantial additions to simulation capabilities. Features added to improve the realism of the simulated genomes include non-crossover recombination and provision of species-specific genomic annotations. Through community-driven efforts, we expanded the number of species in the catalog more than three-fold and broadened coverage across the tree of life. During the process of expanding the catalog, we have identified common sticking points and developed best practices for setting up genome-scale simulations. We describe the input data required for generating a realistic simulation, suggest good practices for obtaining the relevant information from the literature, and discuss common pitfalls and major considerations. These improvements to stdpopsim aim to further promote the use of realistic whole-genome population genetic simulations, especially in non-model organisms, making them available, transparent, and accessible to everyone.

bioinformatics↗

bioRxiv2022

Extraordinary selection on the human X chromosome associated with archaic admixture

The X chromosome in non-African human populations shows less diversity and less Neanderthal introgression than expected under the standard neutral model. We analyzed 162 X chromosomes from human males worldwide and discovered 14 chromosomal regions where haplotypes of several hundred kilobases rapidly rose to high frequencies in non-Africans. These observations cannot be explained by neutral genetic drift in realistic demographic scenarios and are only consistent with partial selective sweeps produced by strong selection. Using an approach for inferring individual Neanderthal-derived haplotypes, which do not rely on an archaic reference genome, we further discover that the swept haplotypes are devoid of the archaic ancestry otherwise typical of the affected chromosomal regions. The ancient Ust-Ishim male carries its expected proportion of these haplotypes, implying that the sweeps must have occurred between 45,000 and 55,000 years ago. Finally, we find that the chromosomal positions of sweeps overlap previously reported hotspots of selection in great ape evolution. We propose that this puzzling combination of observations points to a general mechanism of positive selection unique to the X chromosome.

evolutionary biology↗

bioRxiv2022

Quantifying the fraction of new mutations that are recessive lethal

The presence and impact of recessive lethal mutations has been widely documented in diploid outcrossing species. However, precise estimates in different species of the proportion of mutations that are recessive lethal remain limited. Here, we attempt to quantify the fraction of new mutations that are recessive lethal using Fit{partial}a{partial}i, a commonly-used method for inferring the distribution of fitness effects (DFE) using the site frequency spectrum. Using simulations, we demonstrate that Fit{partial}a{partial}i cannot accurately estimate the fraction of recessive lethal mutations, as expected given that Fit{partial}a{partial}i assumes that all mutations are additive by default. Consistent with the idea that mis-specification of the dominance model can explain this performance, we find that Fit{partial}a{partial}i can accurately infer the fraction of additive lethal mutations. Moreover, we demonstrate that in both additive and recessive cases, inference of the deleterious non-lethal portion of the DFE is minimally impacted by a small proportion (<10%) of lethal mutations. Finally, as an alternative approach to estimate the proportion of mutations that are recessive lethal, we employ models of mutation-selection-drift balance using existing genomic parameters and segregating recessive lethals estimates for humans and Drosophila melanogaster. In both species, we find that the segregating recessive lethal load can be explained by a very small fraction (<1%) of new nonsynonymous mutations being recessive lethal. Our results refute recent assertions of a much higher recessive lethal mutation fraction (4-5%), while highlighting the need for additional information on the joint distribution of selection and dominance coefficients.

evolutionary biology↗

bioRxiv2021

PRDM9 losses in vertebrates are coupled to the loss of at least three other meiotic genes

In most mammals and likely throughout vertebrates, the gene PRDM9 specifies the locations of meiotic double strand breaks; in mice and humans at least, it also aids in their repair. For both roles, many of the molecular partners remain unknown. Here, we take a phylogenetic approach to identify genes that may be interacting with PRDM9, by leveraging the fact that PRDM9 arose before the origin of vertebrates, but was lost many times, either partially or entirely--and with it, its role in recombination. As a first step, we characterize PRDM9 domain composition across 446 vertebrate species, inferring at least thirteen independent losses. We then use the interdigitation of PRDM9 orthologs across vertebrates to test whether it co-evolved with any of 241 candidate genes co-expressed with PRDM9 in mice or associated with recombination phenotypes in mammals. Accounting for the phylogenetic relationship among species, we find two genes whose presence and absence is unexpectedly coincident with that of PRDM9: ZCWPW1, which was recently shown to facilitate double strand break repair, and its paralog ZCWPW2, as well as more tentative evidence for TEX15 and FBXO47. ZCWPW2 is expected to be recruited to sites of PRDM9 binding; its tight coevolution with PRDM9 across vertebrates suggests that it is a key interactor, with a role either in recruiting the recombination machinery or in double strand break repair. Author SummaryOur understanding of meiotic recombination in mammals has seen great progress over the past 15 years, spurred in part by the convergence of lines of evidence from molecular biology, statistical genetics and evolutionary biology. We now know that in most mammals and likely in many vertebrates, the gene PRDM9 specifies the location of meiotic double strand breaks and that in mice and humans at least, it also aids in their repair. For both roles, however, many of the molecular partners remain unknown. To search for these, we take a phylogenetic approach, leveraging the fact that the complete PRDM9 has been lost at least thirteen times in vertebrates and thus that its presence is interdigitated across species. By this approach, we identify two genes whose presence or absence across vertebrates is coupled to the presence or absence of PRDM9, ZCWPW1 and ZCWPW2, as well as two genes for which the evidence is weaker, TEX15 and FBXO47. ZCWPW1 was recently shown to be recruited to sites of PRDM9 binding and to aid in the repair of double strand breaks. ZCWPW2 is likely recruited to sites of PRDM9 binding as well; its tight coevolution with PRDM9 across vertebrates suggests that it plays an important role either in double strand break formation, potentially as the missing link that recruits the recombination machinery to sites of PRDM9 binding, or in double strand break repair.

evolutionary biology↗

bioRxiv2021

Recombination facilitates adaptive evolution in rhizobial soil bacteria

Homologous recombination is expected to increase natural selection efficacy by decoupling the fate of beneficial and deleterious mutations and by readily creating new combinations of beneficial alleles. Here, we investigate how the proportion of amino acid substitutions fixed by adaptive evolution () depends on the recombination rate in bacteria. We analyze 3086 core protein-coding sequences from 196 genomes belonging to five closely-related species of the genus Rhizobium. These genes are found in all species and do not display any signs of introgression between species. We estimate using the site frequency spectrum (SFS) and divergence data for all pairs of species. We evaluate the impact of recombination within each species by dividing genes into three equally sized recombination classes based on their average level of intragenic linkage disequilibrium. We find that varies from 0.07 to 0.39 across species and is positively correlated with the level of recombination. This is both due to a higher estimated rate of adaptive evolution and a lower estimated rate of non-adaptive evolution, suggesting that recombination both increases the fixation probability of advantageous variants and decreases the probability of fixation of deleterious variants. Our results demonstrate that homologous recombination facilitates adaptive evolution measured by in the core genome of prokaryote species in agreement with studies in eukaryotes. Significance statementWhether intraspecific homologous recombination has a net beneficial or detrimental effect on adaptive evolution is largely unexplored in natural bacterial populations. We address this question by evaluating polymorphism and divergence data across the core genomes of 196 bacterial sequences--belonging to five closely related species of the genus Rhizobium. We show that the proportion of amino acid changes fixed due to adaptive evolution () increases with an increased recombination rate. This correlation is observed both in the interspecies and intraspecific comparisons. By using a population genetics approach our results demonstrate that homologous recombination directly impacts the efficacy of natural selection in the core genome of prokaryotes, as previously reported in eukaryotes.

evolutionary biology↗

bioRxiv2019

The genomic architecture of introgression amongsibling species of bacteria

BackgroundGene transfer between bacterial species is an important mechanism for adaptation. For example, sets of genes that confer the ability to form nitrogen-fixing root nodules on host plants have frequently moved between Rhizobium species. It is not clear, though, whether such transfer is exceptional, or if frequent inter-species introgression is typical. To address this, we sequenced the genomes of 196 isolates of the Rhizobium leguminosarum species complex obtained from root nodules of white clover (Trifolium repens). ResultsCore gene phylogeny placed the isolates into five distinct genospecies that show high intra-genospecies recombination rates and remarkably different demographic histories. Most gene phylogenies were largely concordant with the genospecies, indicating that recent gene transfer between genospecies was rare. In contrast, very similar symbiosis gene sequences were found in two or more genospecies, suggesting recent horizontal transfer. The replication and conjugative transfer genes of the plasmids carrying the symbiosis genes showed a similar pattern, implying that introgression occurred by conjugative plasmid transfer. The only other regions that showed strong phylogenetic discordance with the genospecies classification were two small chromosomal clusters, one neighbouring a conjugative transfer system. Phage-related sequences were observed in the genomes, but appeared to have very limited impact on introgression. ConclusionsIntrogression among these closely-related species has been very limited, confined to the symbiosis plasmids and a few chromosomal islands. Both introgress through conjugative transfer, but have been subject to different types of selective forces.

genomics↗

bioRxiv2018

Strong selective sweeps before 45,000BP displaced archaic admixture across the human X chromosome

The X chromosome in non-African populations has less diversity and less Neanderthal introgression than expected. We analyzed X chromosome diversity across the globe and discovered seventeen chromosomal regions, where haplotypes of several hundred kilobases have recently reached high frequencies in non-African populations only. The selective sweeps must have occurred more than 45,000 years ago because the ancient Ust-Ishim male also carries its expected proportion of these haplotypes. Surprisingly, the swept haplotypes are entirely devoid of Neanderthal introgression, which implies that a population without Neanderthal admixture contributed the swept haplotypes. It also implies that the sweeps must have happened after the main interbreeding event with Neanderthals about 55,000 BP. These swept haplotypes may thus be the only genetic remnants of an earlier out-of-Africa event.\n\nOne Sentence SummaryAfter humans expanded out of Africa, the X chromosome experienced a burst of extreme natural selection that removed Neanderthal admixture.

genomics↗