Biology subjects

Szpiech, Z. A.

Publications and source records attributed to Szpiech, Z. A..

At least 19 recordsLinked to original sources

bioRxiv2026

Rapid expansion overcomes inbreeding in cross-hemisphere colonization of Barn Swallows

Switching migratory behavior appears to promote speciation in birds through colonization of their wintering grounds for breeding. However, colonization episodes often fail, especially when they lead to inbreeding depression associated with small population sizes. We studied the dynamics of a new and thriving breeding population of migratory Barn Swallows (Hirundo rustica erythrogaster) that began nesting on their traditional wintering grounds in South America in the 1980s and evolved an "inverse" migration and breeding cycle. We show that in four decades, behavioral flexibility and standing genetic variation have facilitated the establishment of a breeding population that has grown exponentially in abundance and breeding range size. By breeding under bridges and culverts, Barn Swallows exploited ecological opportunities that outweighed the costs of inbreeding and began an independent evolutionary trajectory from their North American relatives.

evolutionary biology↗

bioRxiv2026

A Rarefaction Approach to Identify Local Introgression in a Three Population Tree

The $D$ statistic, also known as the $ABBA-BABA$ statistic, is widely used to detect the presence of archaic genome-wide introgression between two non-sister taxa. $D$ counts the imbalance between the number of biallelic sites where either the second and third taxa (ABBA site) share the derived allele or the first and third taxa (BABA site) share the derived allele in a four taxa tree. Here, the fourth taxon acts as an outgroup to determine the ancestral allele. When there is no introgression, these counts are expected to be equal, and a discordance between counts suggests introgression from the third taxon into either the first or second. D is limited to the detection of genome-wide introgression and exhibits a high false-positive rate when applied to smaller genomic segments. Here, we present a new method, D STatistic with Allelic Rarefaction ($\dstar$), to address these limitations. $\dstar$ uses multiple lineages and does not require an outgroup to calculate the imbalance between the number of alleles found exclusively in the second and third taxa and the number of alleles found exclusively in the first and third taxa. $\dstar$ employs a rarefaction technique to correct for unequal sample-size and allows multiallelic sites. We use simulations to show that $\dstar$ has better precision and recall for detecting introgressed segments of DNA when compared to other methods. We conclude by recovering Denisovan DNA related to immune function in modern day Papuans. Precompiled executables, the manual, source code, and simulation and analysis scripts used in this study can be found at \url{https://github.com/TQ-Smith/DSTAR}

evolutionary biology↗

bioRxiv2026

Historically Small Population Size Limits Purging of Deleterious Mutations in a Conservation-Reliant Species, the Kirtlands Warbler

Strong population contractions can leave a persistent genomic legacy that can influence populations long after their demographic recovery. While bottlenecks facilitate the removal of strongly deleterious mutations, the effectiveness of purging may be limited in historically small populations. The Kirtlands warbler (Setophaga kirtlandii) is a rare North American songbird with an ancestrally small population. After narrowly evading extinction, they are one of few species that have been delisted from federal protections in the USA. Despite their recovery, a previous study showed evidence for recent inbreeding and a high burden of deleterious mutations that may have not been purged despite strong bottlenecks. Historical DNA offers a unique opportunity to understand the consequences of recent demographic declines on genetic diversity. Here, we use DNA from over 100-year-old museum specimens to estimate changes in genetic load in the Kirtlands warblers pre- and post-bottleneck. We validate our results with forward-in-time genetic simulations and explore how sample size and missing data can affect estimates. Both empirical data and simulations suggest a reduced ability to purge deleterious mutations in this historically small population. Our simulations also highlight that limited sampling design and data quality can constrain the ability to detect changes.

evolutionary biology↗

bioRxiv2026

Haplotype-based models improve sweep detection in ancient populations with complex demography

Identifying signatures of positive selection in humans is complicated by demographic processes such as bottlenecks, migration and admixture, all of which can distort or obscure the genomic patterns produced by selective sweeps. Ancient DNA offers a direct window into past allele and haplotype frequencies, yet most sweep scans in ancient populations rely on allele-frequency or site frequency spectrum (SFS) summaries, with limited use of haplotype-based approaches. Here, we evaluate the performance of haplotype and SFS-based methods for detecting selective sweeps under demographic scenarios that reflect the complex history of ancient and modern Europeans. We extend the haplotype-based likelihood framework saltiLASSI to accommodate pseudohaploid ancient genomes, enabling the use of truncated haplotype frequency spectra and their spatial decay to detect sweeps without requiring phased data. Using forward-in-time simulations, we examine sweeps of varying ages, two pulses of admixture with different source proportions, and cases where selection continues or ceases after admixture. We compare saltiLASSI to a widely used SFS-based approach (SweepFinder2). Our results show that haplotype-based likelihood models retain higher power than SFS methods in admixed populations, particularly when sweep haplotypes are introduced through migration or when selection has not had sufficient time to regenerate a clear SFS signature after admixture. These findings highlight the promise of haplotype-based inference for ancient DNA and demonstrate how model-based approaches can improve the detection of historical selective sweeps in populations with complex demographic histories.

genetics↗

bioRxiv2025

The Influence of Demographic History and Genetic Architecture on Complex Traits via Runs of Homozygosity

Runs of homozygosity (ROH) are contiguous genomic regions where all sites are homozygous, inherited from identical haplotypes due to shared ancestry. The number and length of ROH in individuals varies based on population history and sociocultural behaviors. Although often discussed in the context of inbreeding, ROH are ubiquitous in putatively outbred human populations, and their prevalence are associated with multiple complex traits, including height and measures of lung function. Importantly, ROH have been shown to be enriched for deleterious alleles, suggesting a mechanism by which ROH prevalence can influence traits. Here we employ realistic forward-in-time population genetic simulations and a flexible quantitative model of a generic complex phenotype to explore how population history and genetic architecture influence ROH associations with a generic quantitative phenotype. We show that ROH are important for all simulated demographic histories and genetic architectures but especially when phenotypes have a recessive component. This is even more prominent when the rare-allele contribution to the phenotype is upweighted and in high-diversity populations (e.g. African). For a fully recessive phenotype, ROH can account for 25-45% of an individual's total phenotype score, depending on demographic history and rare-allele weight. Our results emphasize the utility of ROH in helping to explain phenotype variation across different population histories and genetic architectures.

evolutionary biology↗

bioRxiv2025

EGGS: Empirical Genotype Generalizer for Samples

SummaryWe introduce Empirical Genotype Generalizer for Samples (EGGS) which accepts empirical genotypes with missing data and replicates the distribution of missing genotypes along the empirical segment in other replicates. The empirical segment must have a number of sites less than the replicate. In addition, EGGS can remove phase, remove polarization, simulate deamination, simulate sequencing error, create pseudohaploids, and convert between Variant Call Format (VCF), ms-style replicates, and EIGENSTRAT/ANCESTRYMAP. When producing VCF files, EGGS is not limited to biallelic sites and assumes all samples are diploid. Availability and ImplementationEGGS is written in the C programming language. Precompiled executables, source code, the manual, and the analysis conducted in the paper are available at https://github.com/TQ-Smith/EGGS

bioinformatics↗

bioRxiv2025

Selection scans and downstream analysis with selscan

Summary statistics based on Extended Haplotype Homozygosity (EHH) are widely used for inferring positive selection in genomes as a result of their ease of use, computational efficiency, and interpretability. These various summary statistics can be applied to single populations or to pairs of populations, can be used with a genetic recombination map or without, and can be applied to phased or unphased data. Although these statistics are straightforward to compute, there lacks clear descriptions on how they relate to one another, how they should be used, and how their resulting outputs should be interpreted. Here, we provide a comprehensive introduction to selection statistics as they are implemented in the widely used software, selscan. In addition to this detailed guide, we implement enhanced normalization procedures and support for gene-based analyses, enabling users to translate selection signals captured by these statistics into gene-level interpretations using BED annotation files, facilitating biologically meaningful insights. We demonstrate the behavior of such statistics on simulated data and highlight best practices by performing an example downstream analysis on data from the 1000 Genomes Project using new features in selscan v3.0. We hope these guidelines will foster reproducibility in the evolutionary genomics community. Precompiled executables and source code for selscan v3.0 can be found at https://github.com/szpiech/selscan.

evolutionary biology↗

bioRxiv2025

Evolutionary Influences on Local Patterns of Genetic Relatedness

Dimensionality reduction methods, such as Principal Components Analysis (PCA) or Multi-dimensional Scaling (MDS), when applied to genomic data, help to visualize the relatedness of individuals in lower dimensional space and are ubiquitous in population-genetic studies. These analyses use genome-wide patterns of variation to provide an "average" picture of genetic structure and relatedness. However, evolutionary processes result in different patterns of relationship among samples in local genomic regions as compared to the genome-wide aggregate. Recently, these local patterns of relatedness have been used to identify regions under selection and inverted segments. Here, we propose a unifying method to dissect these local deviations in genetic relatedness. Our method, Local Decomposition and Similarity to All Regions (LODESTAR), uses Procrustes Analysis to assess the similarity between local MDS results computed using pairwise allele sharing distances or a set of user-defined points. Given two sets of points, Procrustes Analysis computes the optimal rotation and scaling that fits one set of points onto the other, while maintaining the relative relationship between points within both sets. We use the Procrustes statistic to measure the similarity between the two sets of points. We show how this method can be used to explore local relatedness patterns that mirror sampling geography or population stratification by performing Procrustes analysis between local relatedness plots and coordinates representing sampling geography or between local relatedness plots and the genome-wide relatedness plot, respectively. In addition, we show how the variance of samples in lower-dimensional space can capture regions lacking population structure and inverted segments.

evolutionary biology↗

bioRxiv2025

Fast and Memory-Efficient Dynamic Programming Approach for Large-Scale EHH-Based Selection Scans

Haplotype-based statistics are widely used for finding genomic regions under positive selection. At the heart of many such statistics is the computation of extended haplotype homozygosity (EHH), which captures the decay of homozygosity away from a focal site. This computation, repeated for potentially millions of sites, is computationally demanding, as it involves tracking counts of unique haplotypes iteratively over long genomic distances and across many individuals. Because of these computational challenges, existing tools do not scale well when applied to large-scale population datasets, such as the 1000 Genomes Project, or the UK Biobank with 500,000 individuals. Optimizing computation becomes crucial when data sets grow large, especially when handling large sample sizes or generating training data for machine learning algorithms. https://github.com/szpiech/selscan Here, we propose a dynamic programming algorithm that substantially improves runtime and memory usage over existing tools on both real and simulated data. On real phased data, we achieve 5-50x speedup with minimal memory footprint. Our simulations show an even more pronounced performance gap with large populations (up to 15x speedup and 46x memory reduction). EHH-based statistics designed for unphased genotypes run an order of magnitude faster, and multi-parameter support results in 20x runtime improvement. Source code and binaries are available at https://github.com/szpiech/selscan as selscan v2.1.

genomics↗

bioRxiv2024

Nested admixture during and after the Trans-Atlantic Slave Trade on the island of Sao Tome

Human admixture history is rarely a simple process in which distinct populations, previously isolated for a long time, come into contact once to form an admixed population. In this study, we aim to reconstruct the complex admixture histories of the population of Sao Tome, an island in the Gulf of Guinea that was the site of the first slave-based plantation economy, and experienced successive waves of forced and deliberate migration from Africa. We examined 2.5 million SNPs newly genotyped in 96 Sao Tomeans and found that geography alone cannot explain the observed patterns of genetic differentiation within the island. We defined five genetic groups in Sao Tome based on the hypothesis that individuals sharing the most haplotypes are more likely to share similar genetic histories. Using Identical-by-Descent and different local ancestry inference methods, we inferred shared ancestries between 70 African and European populations and each Sao Tomean genetic group. We identified admixture events between admixed groups that were previously isolated on the island, showing how recently admixed populations can be themselves the sources of other admixture events. This study demonstrates how complex admixture and isolation histories during and after the Transatlantic Slave-Trade shaped extant individual genetic patterns at a local scale in Africa.

genetics↗

bioRxiv2024

Differentiating mechanism from outcome for ancestry-assortative mating in admixed human populations

Population genetic theory, and the empirical methods built upon it, often assume that individuals pair randomly for reproduction. However, natural populations frequently violate this assumption, which may potentially confound genome-wide association studies, selection scans, and demographic inference. Within several recently admixed human populations, empirical genetic studies have reported a correlation in global ancestry proportion between spouses, referred to as ancestry-assortative mating. Here, we use forward genomic simulations to link correlations in global ancestry proportion between mates to the underlying mechanistic mate-choice process. We consider the impacts of two types of mate-choice model, using either ancestry-based preferences or social groups as the basis for mate pairing. We find that multiple mate-choice models can produce the same correlations in global ancestry proportion between spouses; however, we also highlight alternative analytic approaches and circumstances in which these models may be distinguished. With this work, we seek to highlight potential pitfalls when interpreting correlations in empirical data as evidence for a particular model of human mating practices, as well as to offer suggestions toward development of new best practices for analysis of human ancestry-assortative mating.

genetics↗

bioRxiv2024

Genotypic and phenotypic consequences of domestication in dogs

Runs of homozygosity (ROH) are genomic regions that arise when two copies of identical haplotypes are inherited from a shared common ancestor. In this study, we leverage ROH to identify associations between genetic diversity and non-disease phenotypes in Canis lupus familiaris (dogs). We find significant association between the ROH inbreeding coefficient (FROH) and several phenotypic traits. These traits include height, weight, lifespan, muscled, white coloring of the head and chest, furnishings, and fur length. After correcting for population structure, we identified more than 45 genes across the examined quantitative traits that exceed the threshold for suggestive significance. We observe distinct distributions of inbreeding and elevated levels of long ROH in modern breed dogs compared to more ancient breeds, which aligns with breeding practices during Victorian era breed establishment. Our results highlight the impact of non-additive variation and of polygenicity on complex quantitative phenotypes in dogs due to domestication and the breed formation bottleneck.

evolutionary biology↗

bioRxiv2023

The Maintenance of Deleterious Variation in Wild Chinese Rhesus Macaques

Understanding how deleterious variation is shaped and maintained in natural populations is important in conservation and evolutionary biology, as decreased fitness caused by these deleterious mutations can potentially lead to an increase in extinction risk. It is known that demographic processes can influence these patterns. For example, population bottlenecks and inbreeding increase the probability of inheriting identical-by-descent haplotypes from a recent common ancestor, creating long tracts of homozygous genotypes called runs of homozygosity (ROH), which have been associated with an accumulation of mildly deleterious homozygotes. Counter intuitively, positive selection can also maintain deleterious variants in a population through genetic hitchhiking. Here we analyze the whole genomes of 79 wild Chinese rhesus macaques across five sub-species and characterize patterns of deleterious variation with respect to ROH and signals of recent positive selection. We show that the fraction of homozygotes occurring in long ROH is significantly higher for deleterious homozygotes than tolerated ones, whereas this trend is not observed for short and medium ROH. This confirms that inbreeding, by generating these long tracts of homozygosity, is the main driver of the high burden of homozygous deleterious alleles in wild macaque populations. Furthermore, we show evidence that homozygous LOF variants are being purged. Next, we identify 7 deleterious variants at high frequency in regions putatively under selection near genes involved with olfaction and other processes. Our results shed light on how evolutionary processes can shape the distribution of deleterious variation in wild non-human primates. SignificanceOur results offer insights into the relationship between demographic and evolutionary processes and the maintenance of deleterious alleles in wild rhesus macaques. We demonstrate how inbreeding and recent positive selection can contribute to the maintenance of deleterious variants in wild non-human primate populations. Given that deleterious variation can reduce individuals reproductive fitness and contribute to extinction risks, this study is particularly relevant in the context of conservation of wild endangered species.

evolutionary biology↗

bioRxiv2023

Genomic signatures of adaptation in native lizards exposed to human-introduced fire ants

Understanding the process of genetic adaptation in response to human-mediated ecological change will help elucidate the eco-evolutionary impacts of human activity. Red fire ants (Solenopsis invicta) spread across Southeastern USA since their accidental introduction via Port Mobile, Alabama in the 1930s, serving today as both novel venomous predator and novel toxic prey to native eastern fence lizards (Sceloporus undulatus). To identify potential signatures of genetic adaptation in lizards to invasive fire ants, we generated whole genome sequencing data from 420 native fence lizards sampled across three populations, two of which had not been invaded by fire ants (in Tennessee and Arkansas) and one which had been invaded for [~]70 years (Alabama). We detected signatures of positive selection exclusive to the exposed Alabama population for genetic variants overlapping genes related to the membrane attack complex of the complement immune system, growth factor pathways, and morphological development. Prior work identified a relationship between increased lizard survival of fire ant attack and longer hind limbs, which lizards use to remove ants from their bodies. Furthermore, we conducted a genome-wide association study with 381 Alabama lizards to identify 24 hind limb length-associated genetic loci. For two loci, positive-effect alleles occur in high frequency and overlap genomic regions that are highly differentiated from the populations naive to fire ants. Collectively, these findings represent plausible genetic adaptations in response to fire ant invasion, whereby morphological differentiation may increase survival against swarming ants and altered immune responses may allow the exploitation of a novel, toxic food resource. Significance statementHuman activity can force interactions between species from distinct ecological backgrounds. These interactions can consequently impose novel selective pressures on endemic populations via predation or disruption of ecological niches through community-wide effects. While some endemic taxa have been able to adapt biologically to these disruptions, we do not have a full understanding of the underlying genetic processes that may allow it. Here we identify genomic signatures of recent adaptation nearby genes involved in morphological and immunological processes in native fence lizards that are consistent with pressures imposed by the venomous, predatory fire ants introduced by humans. These signatures are largely absent from lizard populations that are naive to fire ants.

evolutionary biology↗

bioRxiv2023

Genomic consequences of isolation and inbreeding in an island dingo population

Dingoes come from an ancient canid lineage that originated in East Asia around 8000-11,000 years BP. As Australias largest terrestrial predator, dingoes play an important ecological role. A small, protected population exists on a world heritage listed offshore island, Kgari (formerly Fraser Island). Concern regarding the persistence of dingoes on Kgari has risen due to their low genetic diversity and elevated inbreeding levels. However, whole-genome sequencing data is lacking from this population. Here, we include five new whole-genome sequences of Kgari dingoes. We analyze a total of 18 whole genome sequences of dingoes sampled from mainland Australia and Kgari to assess the genomic consequences of their demographic histories. Long (>1 Mb) runs of homozygosity (ROH) -- indicators of inbreeding -- are elevated in all sampled dingoes. However, Kgari dingoes showed significantly higher levels of very long ROH (>5 Mb), providing genomic evidence for small population size, isolation, inbreeding, and a strong founder effect. Our results suggest that, despite current levels of inbreeding, the Kgari population is purging strongly deleterious mutations, which, in the absence of further reductions in population size, may facilitate the persistence of small populations despite low genetic diversity and isolation. However, there may be little to no purging of mildly deleterious alleles, which may have important long-term consequences, and should be considered by conservation and management programs. SIGNIFICANCEA long-standing question in conservation genetics is whether long-term isolation and elevated levels of inbreeding always leads to inevitable population extinction. Here we conduct the first-ever whole-genome analysis of a population of dingoes living in long-term isolation on an island off the coast of Australia (Kgari). We show that these animals are beset by very low genetic diversity, likely the result of extensive inbreeding, and an elevated number of deleterious homozygotes. However, our results suggest that these dingoes are likely purging highly deleterious alleles, which may have allowed them to persist long term despite their extremely small population (<200 individuals).

evolutionary biology↗

bioRxiv2022

The admixture histories of Cabo Verde

From the 15th to the 19th century, the Trans-Atlantic Slave-Trade (TAST) influenced the genetic and cultural diversity of numerous populations. We explore genomic and linguistic data from the nine islands of Cabo Verde, the earliest European colony of the era in Africa, a major Slave-Trade platform between the 16th and 19th centuries, and a previously uninhabited location ideal for investigating early admixture events between Europeans and Africans. Using local-ancestry inference approaches, we find that genetic admixture in Cabo Verde occurred primarily between Iberian and certain Senegambian populations, although forced and voluntary migrations to the archipelago involved numerous other populations. Inter-individual genetic and linguistic variation recapitulates the geographic distribution of individuals birth-places across Cabo Verdean islands, following an isolation-by-distance model with reduced genetic and linguistic effective dispersals within the archipelago, and suggesting that Kriolu language variants have developed together with genetic divergences at very reduced geographical scales. Furthermore, based on approximate bayesian computation inferences of highly complex admixture histories, we find that admixture occurred early on each island, long before the 18th-century massive TAST deportations triggered by the expansion of the plantation economy in Africa and the Americas, and after this era mostly during the abolition of the TAST and of slavery in European colonial empires. Our results illustrate how shifting socio-cultural relationships between enslaved and non-enslaved communities during and after the TAST, shaped enslaved-African descendants genomic diversity and structure on both sides of the Atlantic.

genetics↗

bioRxiv2021

selscan 2.0: scanning for sweeps in unphased data

SummarySeveral popular haplotype-based statistics for identifying recent or ongoing positive selection in genomes require knowledge of haplotype phase. Here we provide an update to selscan which implements a re-definition of these statistics for use in unphased data. Availability and ImplementationSource code and binaries freely available at https://github.com/szpiech/selscan, implemented in C/C++ and supported on Linux, Windows, and MacOS. Contactszpiech@psu.edu Supplemental InformationOnline supplemental information available

evolutionary biology↗

bioRxiv2021

A spatially aware likelihood test to detect sweeps from haplotype distributions

The inference of positive selection in genomes is a problem of great interest in evolutionary genomics. By identifying putative regions of the genome that contain adaptive mutations, we are able to learn about the biology of organisms and their evolutionary history. Here we introduce a composite likelihood method that identifies recently completed or ongoing positive selection by searching for extreme distortions in the spatial distribution of the haplotype frequency spectrum along the genome relative to the genome-wide expectation taken as neutrality. Furthermore, the method simultaneously infers two parameters of the sweep: the number of sweeping haplotypes and the "width" of the sweep, which is related to the strength and timing of selection. We demonstrate that this method outperforms the leading haplotype-based selection statistics. As a positive control, we apply it to two well-studied human populations from the 1000 Genomes Project and examine haplotype frequency spectrum patterns at the LCT and MHC loci. We also apply it to a data set of brown rats sampled in NYC and identify genes related to olfactory perception. To facilitate use of this method, we have implemented it in user-friendly open source software.

evolutionary biology↗