Biology subjects

Hartfield, M.

Publications and source records attributed to Hartfield, M..

10 recordsLinked to original sources

bioRxiv2026

Genome assemblies of climatically distinct Aegilops mutica reveal extensive structural variation

Bread wheat harbours low genetic diversity due to bottlenecks during speciation, domestication, and selection; wild relatives therefore provide critical reservoir for climate-resilient breeding. Aegilops mutica, one of the few self-incompatible diploids in the Aegilops-Triticum species complex, is a putative parent in the homoploid hybridisation event that formed the D-genome clade and is a proven donor of disease resistance, winter hardiness and grain zinc accumulation. Ae. mutica is globally endangered, with a reference-quality genome available for only a single Central Anatolian accession. Using HiFi sequencing, we generated genome assemblies from two accessions from opposite extremes of the species' range: western Turkiye and Armenia. The four haploid assemblies recovered ~93% complete BUSCOs and comprised ~81% repetitive sequence, predominantly LTR retrotransposons (~55%), closely matching the reference. Comparison against the reference identified 145,871-155,535 structural variants per haplotype, including an 8.4 Mb inversion on chromosome 6T. Between 96,860 and 105,472 structural variants segregated between haplotypes within individuals and classic domestication loci did not overlap with any large structural variants. These assemblies and structural variant catalogue extend genomic resources for Ae. mutica, providing a basis for targeted introgression into wheat and conservation of a species for which populations in the South Caucasus have severely declined.

genomics↗

bioRxiv2026

Selfing-aware demographic inference highlights local population structure and bottlenecks in Hawaiian Caenorhabditis elegans

Demographic inference based on sequentially Markovian coalescent (SMC) model is widely used for disentangling the evolutionary history of species and populations. However, the genetic effects of self-fertilization, including the expected reduction of population-level genetic diversity and hence effective population size (Ne), are often ignored in demographic inference, despite the fact that selfing is a common reproductive mode in both invertebrates and plants. To investigate how self-fertilization could bias demographic inference, we apply eSMC2, a selfing-aware demographic inference method, to Hawaiian populations of Caenorhabditis elegans, a predominantly self-fertilizing nematode. Using an expanded dataset that contains more Hawaiian strains than in previous studies, we recovered previously reported genetic groups, including one largely consisting of strains from the Big Island. Population substructure is also detected among these Big Island subpopulations, highlighting the importance of identifying subgroups to avoid misinterpretations of demography. For different Big Island subpopulations, we estimate high selfing rates compatible with previous studies and infer consistent population declines. Population sizes inferred using eSMC2 are smaller than those inferred using PSMC', which does not account for selfing. However, rescaling PSMC' parameters to account for self-fertilization produces a similar demographic trajectory as eSMC2 inference. Our study thus demonstrates how one can account for effects of selfing when using SMC-based methods. It also indicates that the Hawaiian group shows population declines similar to those previously found outside Hawaii.

evolutionary biology↗

bioRxiv2024

How do self-fertilising and facultative sexual populations differ in mutation accumulation?

Self-fertilisation and asexual reproduction are both hypothesised to cause long-term extinction due to inefficient selection against deleterious mutations. Self-fertilisation can counter these effects through creating homozygous genotypes and purging deleterious mutations. Although complete asexuality lacks meiotic gene exchange, mitotic gene conversion creates homozygous regions that could limit deleterious mutation accumulation in an analogous manner. We compare mutation accumulation in self-fertilising and facultative sexual populations subject to mitotic gene conversion, and quantify the efficacy of purging in the latter. We first show analytically that purging is most effective with high levels of asexuality and gene conversion, and when deleterious mutations are recessive. We further show using simulations that, when mitotic gene conversion becomes sufficiently high in obligate asexuals, there is a reduction in the mutation count and a jump in homozygosity, reflecting purging. However, this mechanism is not necessarily as efficient at purging under high self-fertilisation, and elevated rates of mitotic gene conversion seem to be needed for widespread purging compared to empirical estimates. If gene conversion rates are allowed to evolve, then elevated rates that increase mean fitness can arise, but only if there is sufficient variance in the gene conversion rate. Conversely, if gene conversion rates are already high and rates are not constrained then they will slightly decrease, reducing mean fitness. Significance StatementAsexuality has been argued to be an evolutionary dead end, due to a lack of gene exchange causing inefficient selection acting against deleterious mutations. It has been proposed that asexuals can counter these negative effects through mitotic gene conversion, which exposes mutations to selection within individual lineages. Here, we theoretically investigate how effective this mechanism is. We compare results to those obtained when individuals reproduce by self-fertilisation, which has similar effects on exposing deleterious variants. While mitotic gene conversion can be effective in removing recessive deleterious mutations, high rates are required (that are not necessarily maintained by selection) and it is not always as effective as selfing.

evolutionary biology↗

bioRxiv2022

Polygenic selection to a changing optimum under self-fertilisation

Many traits are polygenic, affected by multiple genetic variants throughout the genome. Selection acting on these traits involves co-ordinated allele- frequency changes at these underlying variants, and this process has been extensively studied in random-mating populations. Yet many species self- fertilise to some degree, which incurs changes to genetic diversity, recombination and genome segregation. These factors cumulatively influence how polygenic selection is realised in nature. Here, we use analytical modelling and stochastic simulations to investigate to what extent self-fertilisation affects polygenic adaptation to a new environment. Our analytical solutions show that while selfing can increase adaptation to an optimum, it incurs linkage disequilibrium that can slow down the initial spread of favoured mutations due to selection interference, and favours the fixation of alleles with opposing trait effects. Simulations show that while selection interference is present, high levels of selfing (at least 90%) aids adaptation to a new optimum, showing a higher long-term fitness. If mutations are pleiotropic then only a few major-effect variants fix along with many neutral hitch-hikers, with a transient increase in linkage disequilibrium. These results show potential advantages to self-fertilisation when adapting to a new environment, and how the mating system affects the genetic composition of polygenic selection. Author SummaryMany biological traits of scientific interest are polygenic, which are influenced by multiple genetic variants present throughout the genome. Emerging whole-genome data from several species is shedding light on how such traits respond to selection, traditionally through co-ordinated changes in variant frequencies. However, many species in nature reproduce via self-fertilisation, where hermaphrodite individuals produce both male and female gametes that can be used to propagate without mates. This reproductive mode can reduce population-level diversity and the reassorting effects of recombination, which affects how polygenic traits respond to selection. In this paper, we theoretically explore how polygenic selection is realised under self-fertilisation, following a shift in the environment. We first show analytically how the mating-system affects the dynamics of polygenic selection, showing that there are two competing effects. First, it can expose mutations to selection more quickly, strengthening adaptation to a changing environment. Conversely, it can reduce the efficacy of selection through weakening the efficacy of recombination. We then use multi-locus stochastic simulations to investigate outcomes under more realistic scenarios, and find that high selfing can lead to higher fitness in the long-term, in contrast to classic expectations. We also investigate how many traits each variant influences, a property known as pleiotropy. If pleiotropy is absent we see that under very high levels of self-fertilisation, populations fix mutations with opposite effects on a trait. If pleiotropy is present then we instead see only a few major-effect genetic variants fixing in the population, alongside many neutral mutations. These findings provide insights into how natural populations adapt to changing environments.

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↗

bioRxiv2022

Demes: a standard format for demographic models

Understanding the demographic history of populations is a key goal in population genetics, and with improving methods and data, ever more complex models are being proposed and tested. Demographic models of current interest typically consist of a set of discrete populations, their sizes and growth rates, and continuous and pulse migrations between those populations over a number of epochs, which can require dozens of parameters to fully describe. There is currently no standard format to define such models, significantly hampering progress in the field. In particular, the important task of translating the model descriptions in published work into input suitable for population genetic simulators is labor intensive and error prone. We propose the Demes data model and file format, built on widely used technologies, to alleviate these issues. Demes provides a well-defined and unambiguous model of populations and their properties that is straightforward to implement in software, and a text file format that is designed for simplicity and clarity. We provide thoroughly tested implementations of Demes parsers in multiple languages including Python and C, and showcase initial support in several simulators and inference methods. An introduction to the file format and a detailed specification are available at:https://popsim-consortium.github.io/demes-spec-docs/.

genetics↗

bioRxiv2020

Using singleton densities to detect recent selection in Bos taurus

Many quantitative traits are subject to polygenic selection, where several genomic regions undergo small, simultaneous changes in allele frequency that collectively alter a phenotype. The widespread availability of genome data, along with novel statistical techniques, has made it easier to detect these changes. We apply one such method, the Singleton Density Score, to the Holstein breed of Bos taurus to detect recent selection (arising up to around 740 years ago). We identify several genes as candidates for targets of recent selection, including some relating to cell regulation, catabolic processes, neural-cell adhesion and immunity. We do not find strong evidence that three traits that are important to humans - milk protein content, milk fat content, and stature - have been subject to directional selection. Simulations demonstrate that since B. taurus recently experienced a population bottleneck, singletons are depleted so the power of SDS methods are reduced. These results inform on which genes underlie recent genetic change in B. taurus, while providing information on how polygenic selection can be best investigated in future studies. Impact statementMany traits of ecological or economic importance (including height, disease propensity, climatic adaptation) are polygenic. That is, they are affected by a large number of genetic variants, with each one only making a small contribution to a trait, but collectively influence variation. As selection acts on all of these variants simultaneously, it only changes the frequency of each one by a small amount, making it hard to detect such selection from genome data. This situation has changed in recent years, with the proliferation of whole-genome data from many individuals, along with the development of methods to detect the subtle effects of polygenic selection. Here, we use data from 102 genomes from domesticated cattle (Bos taurus) that has experienced intense artificial selection since domestication, and test whether we can detect signatures of recent selection (arising up to 740 years ago). Domesticated species are appealing for this kind of study, as they are subject to extensive genome sequencing studies, and genetic variants can be related to traits under selection. We carried out our analysis in two parts. We first performed a genome-wide scan to find individual genetic regions that show signatures of recent selection. We identify some relating to cell regulation, catabolic processes, neural-cell adhesion and immunity. In the second part, we then analysed genetic regions associated with three key traits: milk protein content, milk fat content, and stature. We tested whether these regions collectively showed a signature of selection, but did not find a significant result in either case. Simulations suggest that the domestication history of cattle affected the power of these methods. We end with a discussion on how to best detect polygenic selection in future studies.

evolutionary biology↗

bioRxiv2019

Approximating the coalescent under facultative sex

Genome studies of facultative sexual species, which can either reproduce sexually or asexually, are providing insight into the evolutionary consequences of mixed reproductive modes. It is currently unclear to what extent the evolutionary history of facultative sexuals genomes can be approximated by the standard coalescent, and if a coalescent effective population size Ne exists. Here, I determine if and when these approximations can be made. When sex is frequent (occurring at a frequency much greater than 1/N per reproduction per generation, for N the actual population size), the underlying genealogy can be approximated by the standard coalescent, with a coalescent Ne {approx} N. When sex is very rare (at frequency much lower than 1/N), approximations for the pairwise coalescent time can be obtained, which is strongly influenced by the frequencies of sex and mitotic gene conversion, rather than N. However, these terms do not translate into a coalescent Ne. These results are used to discuss the best sampling strategies for investigating the evolutionary history of facultative sexual species.

evolutionary biology↗

bioRxiv2018

Selective sweeps under dominance and self-fertilisation

A major research goal in evolutionary genetics is to uncover loci experiencing positive selection. One approach involves finding selective sweeps patterns, which can either be hard sweeps formed by de novo mutation, or soft sweeps arising from recurrent mutation or existing standing variation. Existing theory generally assumes outcrossing populations, and it is unclear how dominance affects soft sweeps. We consider how arbitrary dominance and inbreeding via self-fertilisation affect hard and soft sweep signatures. With increased self-fertilisation, they are maintained over longer map distances due to reduced effective recombination and faster beneficial allele fixation times. Dominance can affect sweep patterns in outcrossers if the derived variant originates from either a single novel allele, or from recurrent mutation. These models highlight the challenges in distinguishing hard and soft sweeps, and propose methods to differentiate between scenarios.

evolutionary biology↗

bioRxiv2017

The Facultative Sex Coalescent with Crossing Over Recombination and Multi-Site Gene Conversion

Under neutrality, linkage disequilibrium (LD) results from physically linked sites having non-independent coalescent histories. In obligately sexual organisms, meiotic recombination is the dominant force separating linked variants from one another, and thus in determining the decay of LD with physical distance. In facultatively sexual diploid organisms that principally reproduce clonally, mechanisms of mitotic exchange are expected to become relatively more important in shaping LD. Here we outline mathematical and computational models of a facultative-sex coalescent process that includes meiotic and mitotic recombination, via both crossovers and gene conversion, to determine how LD is affected with facultative sex. We demonstrate that the degree to which LD is broken down by meiotic recombination simply scales with the probability of sex if it is sufficiently high (much greater than 1/N for N the population size). However, with very rare sex (occurring with frequency on the order of 1/N), mitotic gene conversion plays a particularly important and complicated role because it both breaks down associations between sites and removes within-individual diversity. Strong population structure under rare sex leads to lower average LD values than in panmictic populations, due to the influence of low-frequency polymorphisms created by allelic sequence divergence acting in individual subpopulations. These analyses provide information on how to interpret observed LD patterns in facultative sexuals, and determine what genomic forces are likely to shape them.

evolutionary biology↗