Biology subjects

Lohse, K.

Publications and source records attributed to Lohse, K..

At least 19 recordsLinked to original sources

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↗

bioRxiv2026

Tuning the SMC: efficient simulation and the structure of ARGs

Sequentially Markovian Coalescent (SMC) models are a central element of contemporary population genetics, underlying many inferential methods. While the SMC has been shown to closely approximate the canonical Coalescent with Recombination (CwR) in terms of low-dimensional, two-locus summaries, its effects on the deeper structural properties of Ancestral Recombination Graphs (ARGs) are less well understood. Here, we define a general SMC approximation, SMC(k), in which a single parameter k controls the physical scale over which common-ancestor events between non-overlapping ancestral segments are permitted. The model encompasses the standard SMC and SMC' as special cases and converges to the CwR as k increases, providing a tunable trade-off between computational efficiency and fidelity to the full recombination process. Using recently developed summaries of ARG structure, we show that SMC approximations systematically truncate the persistence of ancestral haplotypes across the genome, despite preserving marginal coalescent properties, and that increasing k progressively recovers this long-range ancestral structure. We implement the SMC(k) in msprime and show that, for small samples, it makes whole-chromosome simulation in species with large population-scaled recombination rates several orders of magnitude faster than the CwR. Finally, we use SMC simulations for chromosome-scale parametric bootstrapping of demographic inference and find that the SMC' captures uncertainty in SFS-based estimates remarkably well, with only modest changes as k increases despite substantial differences in long-range ARG structure. Thus, the importance of SMC approximation error depends strongly on which properties of ancestry are relevant to the downstream analysis.

genomics↗

bioRxiv2026

diempy: fast and reference-free genome polarisation

Most ancestry-assignment methods rely on putatively pure reference panels, which are often unrealistic and bias inference. The genome polarisation algorithm diem, introduced previously, avoids reference panels by jointly inferring the polarity of common allelic states and quantifying variant diagnosticity via an expectation-maximisation procedure. Here we present diempy, an efficient python implementation of diem coupled with tools that turn polarised calls into analysis-ready outputs. diempy offers lossless VCF-to-diem BED conversion; ploidy-aware handling of individuals and chromosomes; flexible masking of sites, regions and individuals; and interactive visualisation of polarised genomes, hybrid indices, clines and ternary plots. Post-processing functions include DI thresholding, kernel smoothing, and automatic detection and run-length encoding of contiguous ancestry tracts. BED-based I/O facilitates integration with population-genomic workflows (e.g. filtering by annotation or ploidy). These features make reference-free genome polarisation with diempy practical and reproducible for studies of population structure, admixture and species barriers.

evolutionary biology↗

bioRxiv2025

Genomic incompatibilities are persistent barriers when speciation happens with gene flow in Formica ants

A current goal of speciation research is to identify the loci underlying reproductive barriers between species. Locating such barrier loci in empirical data is difficult due to the often complex demographic history of diverged taxa and the heterogeneity in evolutionary forces across the genome. Here we take advantage of a natural case of hybridization between two wood ant species (Formica aquilonia and F. polyctena) to identify regions of reduced long-term gene flow using demographically explicit scans of non-admixed genomes. In addition we identify candidate Bateson-Dobzhansky-Muller incompatibilities (BDMIs) through an imbalanced recombinant haplotype frequency analysis of natural F. aquilonia x F. polyctena hybrid genomes. Both approaches find barriers that are scattered across the genome. Furthermore, candidate BDMIs significantly overlap with the long-term barriers identified by gIMble, indicating that incompatibilities have persisted despite divergence with gene flow between the wood ant species. Intriguingly, BDMIs interact in a network and the number of pairwise interactions a BDMI has correlates with its long-term barrier strength: hub-like BDMIs with many pairwise interactions reduce gene flow more effectively. Finally in regards to function, long-term barriers identified by gIMble arise outside regions of both gene coding sequences (CDS) and transposable elements. In contrast, regions where long-term barriers and BDMIs co-locate are significantly associated with introns, implying a potential role of alternative splicing or gene regulation in incompatibilities, rather than CDS divergence. Overall, our results highlight the underappreciated impact of multilocus BDMIs and the need to consider network connectivity of BDMIs in future work. SignificanceDetecting barrier loci that reduce gene flow between closely related species is a common goal of speciation research. However, reliable detection of barrier loci is difficult due to confounding signals in genomic data. Here we take advantage of two different, recently developed approaches and find that barrier loci between wood ant species are scattered across the genome, and despite on-going gene flow, maintain two distinct species. We reveal that genomic regions that are incompatible between the two species can act as persistent barriers, despite theoretical predictions for their collapse under gene flow. Connectivity between incompatibilities also seems to play an important role in barrier persistence. These results highlight the need to consider connectivity between barrier loci in future speciation research.

evolutionary biology↗

bioRxiv2024

Genomic regions of current low hybridisation mark long-term barriers to gene flow in scarce swallowtail butterflies

Many closely related species continue to hybridise after millions of generations of divergence. However, the extent to which current patterning in hybrid zones connects back to the speciation process remains unclear: does evidence for current multilocus barriers support the hypothesis of speciation due to multilocus divergence? We analyse whole-genome sequencing data to investigate the speciation history of the scarce swallowtails Iphiclides podalirius and I. feisthamelii, which abut at a narrow ([~]25 km) contact zone north of the Pyrenees. We first quantify the heterogeneity of effective migration rate under a model of isolation with migration, using genomes sampled across the range to identify long-term barriers to gene flow. Secondly, we investigate the recent ancestry of individuals from the hybrid zone using genome polarisation and estimate the coupling coefficient under a model of a multilocus barrier. We infer a low rate of long-term gene flow from I. feisthamelii into I. podalirius the direction of which matches the admixture across the hybrid zone and complete reproductive isolation across{approx} 33% of the genome. Our contrast of recent and long-term gene flow shows that regions of low recent hybridisation are indeed enriched for long-term barriers which maintain divergence between these hybridising sister species. This paves the way for future analysis of the evolution of reproductive isolation along the speciation continuum. Author summaryEfforts to understand how new species evolve typically approach the problem through either: 1) investigating patterns of genetic exchange across hybrid zones -- where closely related species interbreed -- or 2) modelling the demographic history of closely related species. Both approaches are capable of quantifying variation in genetic exchange, or gene flow, along the genome to identify regions of reproductive isolation; yet they leverage genetic signatures across vastly different timescales. The former exploits very recent signatures, while the latter averages long-term signatures over the history of divergence. Hence, we can contrast the genomic distribution of barriers acting on these very different timescales to test how patterns of gene flow change across the speciation continuum. Here we use this strategy to capture the speciation dynamics of a pair of hybridising papilionid butterflies. Our results show that not only are these species continuing to produce hybrids after more than a million years since the onset of divergence, but there is a significant degree of concordance between patterns of gene flow observed along the genome across time scales.

evolutionary biology↗

bioRxiv2024

Genomic analyses in Drosophila do not support the classic allopatric model of speciation.

The allopatric model of speciation has dominated our understanding of speciation biology and biogeography since the Modern Synthesis. It is uncontroversial because reproductive isolation may readily emerge as a by-product of evolutionary divergence during allopatry unopposed by gene flow. Recent genomic studies have found that gene flow between species is common, but whether allopatric speciation is common has rarely been systematically tested across a continuum of closely-related species. Here, we fit a range of demographic models of evolutionary divergence to whole-genome sequence data from 93 pairs of Drosophila species to infer speciation histories and levels of post-divergence gene flow. We find that speciation with gene flow is common, even between currently allopatric pairs of species. Estimates of historical gene flow are not predicted by current range overlap. Whilst evidence for secondary contact is generally limited, a few sympatric pairs showed strong support for a secondary contact model. Our analyses suggest that most speciation processes involve some long-term gene flow, perhaps due to repeated cycles of allopatry and contact, without requiring an extensive allopatric phase.

evolutionary biology↗

bioRxiv2024

Rewinding the ratchet: rare recombination locally rescues neo-W degeneration and generates plateaus of sex-chromosome divergence

Natural selection is less efficient in the absence of recombination. As a result, non-recombining sequences, such as sex chromosomes, tend to degenerate over time. Although the outcomes of recombination arrest are typically observed after many millions of generations, recent neo-sex chromosomes can give insight into the early stages of this process. Here we investigate the evolution of neo-sex chromosomes in the Spanish marbled white butterfly, Melanargia ines, where a Z-autosome fusion has turned the homologous autosome into a non-recombining neo-W chromosome. We show that these neo-sex chromosomes are likely limited to the Iberian population of M. ines, and that they arose around the time when populations in Iberia and North-Africa split, around 1.5 million years ago. Recombination arrest of the neo-W chromosome has led to an excess of premature stop codons and frameshift mutations, while levels of gene expression have remained similar for the neo-W and neo-Z chromosomes, even for genes with loss-of-function mutations. Surprisingly, we identified two regions of[~] 1 Mb at one end of the neo-W that are both less diverged from the neo-Z and less degraded than the rest of the chromosome, suggesting a history of rare but repeated genetic exchange between the two neo-sex chromosomes. These plateaus of neo-sex chromosome divergence suggest that neo-W degradation can be locally reversed by rare recombination between neo-W and neo-Z chromosomes.

evolutionary biology↗

bioRxiv2023

Inferring inter-chromosomal rearrangements and ancestral linkage groups from synteny

Chromosome rearrangements shape the structure of the genome and influence evolutionary processes. Inferring ancestral chromosomes and rearrangements across a phylogenetic tree is therefore an important analysis within evolutionary genetics. One approach to this inference problem is to focus on synteny information, i.e. the co-occurrence of loci on the same chromosome. Although algorithms for inferring ancestral linkage groups (ALGs) and inter-chromosomal rearrangements from synteny have been previously described, they have seldom been applied to modern genome data. Here we implement these algorithms in a command-line tool, syngraph, and evaluate their performance using simulations that include a mix of different rearrangements and types of error. We show that ALGs and rearrangements can be recovered when the rearrangement frequency per-branch is well below the number of chromosomes. We demonstrate that competing models of rearrangement can be inferred by comparing observed results to simulations. Finally, we reanalyse genome assemblies of rhabditid nematodes and find that independent fusions of the same ALGs pose a challenge that is difficult to overcome without gene-order information. Our simulations and analysis of real data demonstrate both the promise and limitations of using synteny information to infer patterns of genome evolution.

evolutionary biology↗

bioRxiv2023

Do chromosome rearrangements fix by genetic drift or natural selection? A test in Brenthis butterflies

Large-scale chromosome rearrangements, such as fissions and fusions, are a common feature of eukaryote evolution. They can have considerable influence on the evolution of populations, yet it remains unclear exactly how rearrangements become established and eventually fix. Rearrangements could fix by genetic drift if they are weakly deleterious or neutral, or they may instead be favoured by positive natural selection. Here we compare genome assemblies of three closely related Brenthis butterfly species and characterise a complex history of fission and fusion rearrangements. An inferred demographic history of these species suggests that rearrangements became fixed in populations with large long-term effective size (Ne). However, we also find large runs of homozygosity within individual genomes and show that a model of population structure with smaller local Ne can reconcile these observations. Using a recently developed analytic framework for characterising hard selective sweeps, we find that chromosome fusions are not enriched for evidence of past sweeps compared to other regions of the genome. Nonetheless, one chromosome fusion in the B. daphne genome is associated with a valley of diversity where genealogical branch lengths are distorted, consistent with a selective sweep. Our results suggest that drift is a stronger force in these populations than suggested by overall genetic diversity, but that the fixation of strongly underdominant rearrangements remains unlikely. Additionally, although chromosome fusions do not typically exhibit signatures of selective sweeps, a single example raises the possibility that natural selection may sometimes play a role in their fixation.

evolutionary biology↗

bioRxiv2022

Ancestrally polymorphic chromosomal inversions as potential drivers of speciation

Chromosomal inversions may play a central role in speciation given their ability to locally reduce recombination and therefore genetic exchange between diverging populations. We analysed long- and short-read whole-genome data from sympatric and allopatric populations of two Drosophila virilis group species, D. montana and D. flavomontana, to understand if inversions have contributed to their divergence. We identified three large alternatively fixed inversions on the X chromosome and one on each of the autosomes 4 and 5. A comparison of demographic models estimated for inverted and non-inverted (colinear) chromosomal regions suggest that these inversions arose before the time of the species split. We detected a low rate of interspecific gene flow (introgression) from D. montana to D. flavomontana, which was further reduced inside inversions and was lower in allopatric than in sympatric populations. Together, these results suggest that the inversions were already present in the common ancestral population, and that gene exchange between the sister taxa was reduced within inversions both before and after the onset of species divergence. Such ancestrally polymorphic inversions may foster speciation by allowing the accumulation of genetic divergence in loci involved in adaptation and reproductive isolation inside inversions early in the speciation process, while gene exchange at colinear regions continues until the evolving reproductive barriers complete speciation. The overlapping X inversions are particularly good candidates for driving the speciation process of D. montana and D. flavomontana, since they harbour strong genetic incompatibilities that were detected in a recent study of experimental introgression. SignificanceChromosomal inversions, genomic rearrangements with reversed gene order, have been extensively studied, but it remains unclear whether and how inversions play a role in species divergence. Analysis of long- and short-read whole-genome data for two Drosophila sister species, D. montana and D. flavomontana, revealed five alternatively fixed inversions. Modelling the demographic history of these inversions shows that they were segregating already in the common ancestor of the species and that they have reduced gene exchange between these sister taxa both before and after the onset of species divergence. These results are compatible with a scenario in which ancestrally polymorphic inversions aid species divergence by protecting divergently selected loci from erosion via gene flow during the earliest stages of speciation.

evolutionary biology↗

bioRxiv2022

Chromosome fissions and fusions act as barriers to gene flow between Brenthis fritillary butterflies

Chromosome rearrangements are thought to promote reproductive isolation between incipient species. However, it is unclear how often, and under what conditions, fission and fusion rearrangements act as barriers to gene flow. Here we investigate speciation between two largely sympatric fritillary butterflies, Brenthis daphne and B. ino. We use a composite likelihood approach to infer the demographic history of these species from whole genome sequence data. We then compare chromosome-level genome assemblies of individuals from each species and identify a total of nine chromosome fissions and fusions. Finally, we fit a demographic model where effective population sizes and effective migration rate vary across the genome, allowing us to quantify the effects of chromosome rearrangements on reproductive isolation. We show that chromosomes involved in rearrangements experienced less effective migration since the onset of species divergence and that genomic regions near rearrangement points have a further reduction in effective migration rate. Our results suggest that the evolution of multiple rearrangements in the B. daphne and B. ino populations, including alternative fusions of the same chromosomes, have resulted in a reduction in gene flow. While fission and fusion of chromosomes are unlikely to be the only processes that have led to speciation between these butterflies, this study shows that these rearrangements can directly promote reproductive isolation and may be involved in speciation when karyotypes evolve quickly.

evolutionary biology↗

bioRxiv2022

Demographically explicit scans for barriers to gene flow using gIMble

Identifying regions of the genome that act as barriers to gene flow between recently diverged taxa has remained challenging given the many evolutionary forces that generate variation in genetic diversity and divergence along the genome, and the stochastic nature of this variation. Progress has been impeded by a conceptual and methodological divide between analyses that infer the demographic history of speciation and genome scans aimed at identifying locally maladaptive alleles i.e. genomic barriers to gene flow. Here we implement genomewide IM blockwise likelihood estimation (gIMble), a composite likelihood approach for the quantification of barriers, that bridges this divide. This analytic framework captures background selection and selection against barriers in a model of isolation with migration (IM) as heterogeneity in effective population size (Ne) and effective migration rate (me), respectively. Variation in both effective demographic parameters is estimated in sliding windows via pre-computed likelihood grids. gIMble includes modules for pre-processing/filtering of genomic data and performing parametric bootstraps using coalescent simulations. To demonstrate the new approach, we analyse data from a well-studied pair of sister species of tropical butterflies with a known history of post-divergence gene flow: Heliconius melpomene and H. cydno. Our analyses uncover both large-effect barrier loci (including well-known wing-pattern genes) and a genome-wide signal of a polygenic barrier architecture. Author summaryAs a fundamental process generating biological diversity, speciation involves the evolution of reproductive isolation and thus the build-up of barriers to genetic exchange among organismal groups. While population genomic data are arguably the only source of information we have about most recent speciation events, the way such data are analysed remains depressingly superficial: population genomic studies of speciation are phrased either as scans for outliers of genetic differentiation, or are based on models of neutral evolution under the constraint of a single genome-wide demography. Here we introduce a new statistical framework called gIMble to estimate the effective rate of gene flow and the effective population sizes along the genome from population genomic data. By capturing genome-wide variation in these two effective demographic parameters, gIMble disentangles the genomic footprints of different modes of selection and provides a direct quantification of the species barrier. To illustrate this framework, we analyse a classic speciation genomic dataset from Heliconius butterflies. We show that barriers to gene flow in this system include both large effect loci - most, but not all, of which were known from functional work - as well as a genome-wide signature of weak-effect polygenic barriers.

evolutionary biology↗

bioRxiv2022

Experimental introgression in Drosophila: asymmetric postzygotic isolation associated with chromosomal inversions and an incompatibility locus on the X chromosome

Interspecific gene flow (introgression) is an important source of new genetic variation, but selection against it can reinforce reproductive barriers between interbreeding species. We used an experimental approach to trace the role of chromosomal inversions and incompatibility genes in preventing introgression between two partly sympatric Drosophila virilis group species, D. flavomontana and D. montana. We backcrossed F1 hybrid females from a cross between D. flavomontana female and D. montana male with the males of the parental species for two generations and sequenced pools of parental strains and their reciprocal 2nd generation backcross (BC2mon and BC2fla) females. Contrasting the observed amount of introgression (mean hybrid index, HI) in BC2 female pools along the genome to simulations under different scenarios allowed us to identify chromosomal regions of restricted and increased introgression. We found no deviation from the HI expected under a neutral null model for any chromosome for the BC2mon pool, suggesting no evidence for genetic incompatibilities in backcrosses towards D. montana. In contrast, the BC2fla pool showed high variation in the observed HI between different chromosomes, and massive reduction of introgression on the X chromosome (large X-effect). This observation is compatible with reduced recombination combined with at least one dominant incompatibility locus residing within the X inversion(s). Overall, our study suggests that genetic incompatibilities arising within chromosomal inversions can play an important role in speciation.

evolutionary biology↗

bioRxiv2022

The genome sequence of the scarce swallowtail, Iphiclides podalirius

The scarce swallowtail, Iphiclides podalirius (Linnaeus, 1758), is a species of butterfly in the family Papilionidae. Here we present a chromosome-level genome assembly for I. podalirius as well as gene and transposable element annotations. We estimate heterozygosity within different partitions of the genome and find a negative correlation between chromosome length and heterozygosity at fourfold-degenerate sites. This high quality genome assembly, the first for any species in the tribe Leptocircini, will be a valuable resource for population genomics in the genus Iphiclides and comparative genomics more generally.

evolutionary biology↗

bioRxiv2021

The genome sequence of the lesser marbled fritillary, Brenthis ino, and evidence for a segregating neo-Z chromosome

The lesser marbled fritillary, Brenthis ino (Rottemburg, 1775), is a species of Palearctic butterfly. Male B. ino individuals have been reported to have between 12 and 14 pairs of chromosomes, a much reduced chromosome number than is typical in butterflies. Here we present a chromosome-level genome assembly for B. ino, as well as gene and transposable element annotations. The assembly is 411.8 Mb in span with contig and scaffold N50s of 9.6 and 29.5 Mb respectively. We also show evidence that the male individual from which we generated HiC data was heterozygous for a neo-Z chromosome, consistent with inheriting 14 chromosomes from one parent and 13 from the other. This genome assembly will be a valuable resource for studying chromosome evolution in Lepidoptera, as well as for comparative and population genomics more generally.

evolutionary biology↗

bioRxiv2021

Estimating the rates of crossover and gene conversion from individual genomes

Recombination can occur either as a result of crossover or gene conversion events. Population genetic methods for inferring the rate of recombination from patterns of linkage disequilibrium generally assume a simple model of recombination that only involves crossover events and ignore gene conversion. However, distinguishing the two processes is not only necessary for a complete description of recombination, but also essential for understanding the evolutionary consequences of inversions and other genomic partitions in which crossover (but not gene conversion) is reduced. We present heRho, a simple composite likelihood scheme for co-estimating the rate of crossover and gene conversion from individual diploid genomes. The method is based on analytic results for the distance-dependent probability of heterozygous and homozygous states at two loci. We apply heRho to simulations and data from the house mouse Mus musculus castaneus, a well studied model. Our analyses show i) that the rates of crossover and gene conversion can be accurately co-estimated at the level of individual chromosomes and ii) that previous estimates of the population scaled rate of recombination [Formula] under a pure crossover model are likely biased.

evolutionary biology↗

bioRxiv2021

Chronic stroke sensorimotor impairment is related to smaller hippocampal volumes: An ENIGMA analysis

Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is involved in sensorimotor behavior but has not been widely studied within the context of post-stroke upper limb sensorimotor impairment. The hippocampus is vulnerable to secondary degeneration after stroke, and damage to this region could further weaken sensorimotor circuits, leading to greater chronic sensorimotor impairment. The purpose of this study was to investigate the cross-sectional association between non-lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke. We hypothesized that smaller ipsilesional hippocampal volumes would be associated with worse upper-limb sensorimotor impairment. Cross-sectional T1-weighted brain MRIs were pooled from 357 participants at the chronic stage after stroke (>180 days post-stroke) compiled from 18 research cohorts worldwide in the ENIGMA Stroke Recovery Working Group (age: median = 61 years, interquartile range = 18, range = 23-93; 135 women and 222 men). Sensorimotor impairment was estimated from the Fugl-Meyer Assessment of Upper Extremity scores. Robust mixed-effects linear models were used to test associations between post-stroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni-corrected, p-value < 0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. We also performed an exploratory analysis to test whether sex differences influence the relationship between sensorimotor impairment and hippocampal volume. Upper limb sensorimotor impairment was positively associated with ipsilesional (p = 0.005; d = 0.33) but not contralesional (p = 0.96; d = 0.01) hippocampal volume, such that impairment was worse for participants with smaller ipsilesional hippocampal volume. This association remained significant independent of lesion volume or other covariates (p = 0.001; d = 0.36). Evidence indicates an interaction between sensorimotor impairment and sex for both ipsilesional (p = 0.008; d = -0.29) and contralesional (p = 0.006; d = -0.30) hippocampal volumes, whereby women showed progressively worsening sensorimotor impairment with smaller hippocampal volumes compared to men. The present study has identified a novel association between chronic post-stroke sensorimotor impairment and ipsilesional, but not contralesional, hippocampal volume. This finding was not due to lesion size and may be stronger in women. We also provide supporting evidence that smaller hippocampal volume post-stroke is likely a consequence of ipsilesional damage, which could provide a link between vascular disease and other disorders, such as dementia.

neuroscience↗

bioRxiv2021

Efficient ancestry and mutation simulation with msprime 1.0

Stochastic simulation is a key tool in population genetics, since the models involved are often analytically intractable and simulation is usually the only way of obtaining ground-truth data to evaluate inferences. Because of this necessity, a large number of specialised simulation programs have been developed, each filling a particular niche, but with largely overlapping functionality and a substantial duplication of effort. Here, we introduce msprime version 1.0, which efficiently implements ancestry and mutation simulations based on the succinct tree sequence data structure and tskit library. We summarise msprimes many features, and show that its performance is excellent, often many times faster and more memory efficient than specialised alternatives. These high-performance features have been thoroughly tested and validated, and built using a collaborative, open source development model, which reduces duplication of effort and promotes software quality via community engagement.

genetics↗