Biology subjects

Charmouh, A. P.

Publications and source records attributed to Charmouh, A. P..

4 recordsLinked to original sources

bioRxiv2024

Estimating gene conversion tract length and rate from PacBio HiFi data

Gene conversions are broadly defined as the transfer of genetic material from a donor to an acceptor sequence and can happen both in meiosis and mitosis. They are a subset of non-crossover events and, like crossover events, gene conversion can generate new combinations of alleles and counteract mutation load by reverting germline mutations through GC-biased gene conversion. Estimating gene conversion rate and the distribution of gene conversion tract lengths remains challenging. We present a new method for estimating tract length, rate and detection probability of non-crossover events directly in HiFi PacBio long read data. The method can be used to make inference from sequencing of gametes from a single individual. The method is unbiased even under low single nucleotide variant (SNV) densities and does not necessitate any demographic or evolutionary assumptions. We test the accuracy and robustness of our method using simulated datasets where we vary length of tracts, number of tracts, the genomic SNV density and levels of correlation between SNV density and NCO event position. Our simulations show that under low SNV densities, like those found in humans, only a minute fraction ([~]2%) of NCO events are expected to become visible as gene conversions by moving at least one SNV. We finally illustrate our method by applying it to PacBio sequencing data from human sperm.

genomics↗

bioRxiv2024

Insights into gene conversion and crossing-over processes from long-read sequencing of human, chimpanzee and gorilla testes and sperm

Homologous recombination rearranges genetic information during meiosis to generate new combinations of variants. Recombination also causes new mutations, affects the GC content of the genome and reduces selective interference. Here, we use HiFi long-read sequencing to directly detect crossover and gene conversion events from switches between the two haplotypes along single HiFi-reads from testis tissue of humans, chimpanzees and gorillas as well as human sperm samples. Furthermore, based on DNA methylation calls, we classify the cellular origin of reads to either somatic or germline cells in the testis tissue. We identify 1692 crossovers and 1032 gene conversions in nine samples and investigate their chromosomal distribution. Crossovers are more telomeric and correlate better with recombination maps than gene conversions. We show a strong concordance between a human double-strand break map and the human samples, but not for the other species, supporting different PRDM9-programmed double-strand break loci. We estimate the average gene conversion tract lengths to be similar and very short in all three species (means 40-100 bp, fitted well by a geometric distribution) and that 95-98% of non-crossover events do not involve tracts intersecting with polymorphism and are therefore not detectable. Finally, we detect a GC bias in the gene conversion of both single and multiple SNVs and show that the GC-biased gene conversion affects SNVs flanking crossover events. This implies that gene conversion events associated with crossover events are much longer (estimated above 500 bp) than those associated with non-crossover events. Highly accurate long-read sequencing combined with the classification of reads to specific cell types provides a new, powerful way to make individual, detailed maps of gene conversion and crossovers for any species.

evolutionary biology↗

bioRxiv2023

A general time-in, time-out model for the evolution of nuptial gift-giving

Nuptial gift-giving occurs in several taxonomic groups including insects, snails, birds, squid, arachnids and humans. Although this trait has evolved many times independently, no general framework has been developed to predict the conditions necessary for nuptial gift-giving to evolve. We use a time-in time-out model to derive analytical results describing the requirements necessary for selection to favour nuptial gift-giving. Specifically, selection will favour nuptial gift-giving if the fitness increase caused by gift-giving exceeds the product of expected gift search time and encounter rate of the opposite sex. Selection will favour choosiness in the opposite sex if the value of a nuptial gift exceeds the inverse of the time taken to produce offspring multiplied by the rate at which mates with nuptial gifts are encountered. Selection can differ between the sexes, potentially causing sexual conflict. We further investigate these results using an individual-based model inspired by a system of nuptial gift-giving spiders, Pisaura mirabilis, by estimating the fitness benefit of nuptial gift-giving using experimental data from several studies. Our results provide a general framework for understanding when the evolution of nuptial gift-giving can occur and provide novel insight into the evolution of worthless nuptial gifts, occurring in multiple taxonomic groups with implications for understanding parental investment.

evolutionary biology↗

bioRxiv2022

Inferring the distributions of fitness effects and proportions of strongly deleterious mutations

The distribution of fitness effects is a key property in evolutionary genetics as it has implications for several evolutionary phenomena including the evolution of sex and mating systems, the rate of adaptive evolution, and the prevalence of deleterious mutations. Despite the distribution of fitness effects being extensively studied, the effects of strongly deleterious mutations are difficult to infer since such mutations are unlikely to be present in samples of haplotypes, so genetic data may contain very little information about them. Recent work has attempted to correct for this issue by expanding the classic gamma-distributed model to explicitly account for strongly deleterious mutations. Here, we use simulations to investigate one such method, adding a parameter (plth) to capture the proportion of strongly deleterious mutations. We show that plth can improve the model fit when applied to individual species but can underestimate the true proportion of strongly deleterious mutations. The parameter can also artificially maximize the likelihood when used to jointly infer a distribution of fitness effects from multiple species. As plth and related parameters are used in current inference algorithms, our results are relevant with respect to avoiding model artifacts and improving future tools for inferring the distribution of fitness effects.

bioinformatics↗