Biology subjects

Bailey, N. P.

Publications and source records attributed to Bailey, N. P..

5 recordsLinked to original sources

bioRxiv2026

Expanded unbiased population-genomic summary statistics in pixy

Estimates of population-genetic summary statistics are often computed from variant-only VCFs, which commonly omit invariant sites (i.e. sites with only homozygous reference genotypes across all samples). However, these sites are critical for correctly estimating per site statistics such as nucleotide diversity ({pi}) and between population divergence (dxy). Our software pixy addressed this issue by providing support for computing statistics directly from "all-sites" VCFs that encode invariant positions explicitly (Korunes and Samuk 2021). pixy has since been widely adopted and used in a large variety of population genetic studies. Here we present a major update to pixy, which expands the original tool in four major areas. First, we provide implementations of new estimators of Wattersons {theta} and Tajimas D that are unbiased with respect to missing data. Secondly, we provide support for arbitrary ploidy and multiallelic sites. Third, we introduce a variety of optimizations, including multicore execution and a roughly order-of-magnitude reduction in per-worker memory footprint. Finally, we have broadly modernized our code base, test suite, and community contribution pathway. We validate these new features on simulated polyploid and multiallelic datasets, as well as two empirical datasets (one diploid and one autotetraploid), and benchmark the new multicore scaling. We position pixy relative to contemporary tools and discuss shared limitations of VCF-based estimators. By integrating support for diverse ploidies, allelic complexity, and genome-wide scale in one workflow, pixy provides the population genetics community with a straightforward tool for estimates of key summary statistics that are unbiased with respect to missing data. pixy remains completely open-source (MIT-licensed) and easily installable with the conda package management system.

bioinformatics↗

bioRxiv2025

An evolutionarily conserved laterally acquired toolkit enables microbiota targeting by Trichomonas

Trichomonas species are a diverse group of obligate extracellular symbionts associated with or attributed to various inflammatory diseases. They colonise mucosal surfaces across a wide range of hosts, all of which harbour a resident microbiota. Their evolutionary history likely involved multiple host transfers, including zoonotic events from columbiform birds to mammals. Using comparative transcriptomics, this study examines Trichomonas gallinae co-cultured with Escherichia coli, identifying a molecular toolkit that Trichomonas species may use to interact with bacterial members of the microbiota. Integrating transcriptomic data with comparative genomics and phylogenetics revealed a conserved repertoire of protein-coding genes likely acquired through multiple lateral gene transfers (LGT) in a columbiform-infecting ancestor. These LGT-derived genes encode muramidases, glucosaminidases, and antimicrobial peptides--enzymes and effectors capable of targeting bacterial cell walls, potentially affecting the bacterial microbiota composition across both avian and mammalian hosts. This molecular toolkit suggests that Trichomonas species can actively compete with and exploit their surrounding microbiota for nutrients, potentially contributing to the dysbiosis associated with Trichomonas infections. Their ability to target bacterial populations at mucosal surfaces provides insight into how Trichomonas species may have adapted to diverse hosts and how they could influence inflammatory mucosal diseases in birds and mammals.

molecular biology↗

bioRxiv2022

Mining the human gut microbiome identifies mycobacterial D-arabinan degrading enzymes

Division and degradation of bacterial cell walls requires coordinated action of a myriad of enzymes. This particularly applies to the elaborate cell walls of acid-fast organisms such as Mycobacterium tuberculosis, which consist of a multi-layered cell wall that contains an unusual glycan called arabinogalactan. Enzymes that cleave the O_SCPLOWDC_SCPLOW-arabinan core of this structure have not previously been identified in any organism. We have interrogated the diverse carbohydrate degrading enzymes expressed by the human gut microbiota and uncovered four families of glycoside hydrolases with the capability to degrade the O_SCPLOWDC_SCPLOW-arabinan or O_SCPLOWDC_SCPLOW-galactan components of arabinogalactan. Using novel exo-O_SCPLOWDC_SCPLOW-galactofuranosidases from gut bacteria we generated enriched O_SCPLOWDC_SCPLOW-arabinan and used it to identify D. gadei as a D-arabinan degrader. This enabled the discovery of endo- and exo-acting enzymes that cleave D-arabinan. We have identified new members of the DUF2961 family (GH172), and a novel family of glycoside hydrolases (DUF4185) that display endo-O_SCPLOWDC_SCPLOW-arabinofuranase activity. The DUF4185 enzymes are conserved in mycobacteria and found in many microbes, suggesting that the ability to degrade mycobacterial glycans plays an important role in the biology of diverse organisms. All mycobacteria encode two conserved endo-O_SCPLOWDC_SCPLOW-arabinanases that display different preferences for the O_SCPLOWDC_SCPLOW-arabinan-containing cell wall components arabinogalactan and lipoarabinomannan, suggesting they are important for cell wall modification and/or degradation. The discovery of these enzymes will support future studies into the structure and function of the mycobacterial cell wall.

biochemistry↗

bioRxiv2020

High-altitude adaptation in rhesus macaques

When natural populations split and migrate to different environments, they may experience different selection pressures that can lead to local adaptation. To capture the genomic patterns of a local selective sweep, we develop XP-nSL, a genomic scan for local adaptation that compares haplotype patterns between two populations. We show that XP-nSL has power to detect ongoing and recently completed hard and soft sweeps, and we then apply this statistic to search for evidence of adaptation to high altitude in rhesus macaques. We analyze the whole genomes of 23 wild rhesus macaques captured at high altitude (mean altitude > 4000m above sea level) to 22 wild rhesus macaques captured at low altitude (mean altitude < 500m above sea level) and find evidence of local adaptation in the high-altitude population at or near 303 known genes and several unannotated regions. We find the strongest signal for adaptation at EGLN1, a classic target for convergent evolution in several species living in low oxygen environments. Furthermore, many of the 303 genes are involved in processes related to hypoxia, regulation of ROS, DNA damage repair, synaptic signaling, and metabolism. These results suggest that, beyond adapting via a beneficial mutation in one single gene, adaptation to high altitude in rhesus macaques is polygenic and spread across numerous important biological systems. Impact SummaryWhen positive selection is ongoing or a beneficial mutation has recently fixed in a population, genetic diversity is reduced in the vicinity of the adaptive allele, and we expect to observe long homozygous haplotypes at high frequency. Here we develop a statistic that summarizes these expected patterns and compares between two populations in order to search for evidence of adaptation that may have occurred in one but not the other. We implement this statistic in a popular and easy-to-use software package, and then apply it to study adaptation to high altitude in rhesus macaques. Extreme environments pose a challenge to life on multiple fronts. Very high-altitude environments are one such example, with low atmospheric oxygen, increased ultraviolet light exposure, harsh temperatures, and reduced nutrition availability. In spite of these challenges, many plants and animals, including humans, have genetically adapted to cope with these hardships. Here we study two populations of rhesus macaques, one living at high altitude and one living close to sea level. We apply our novel statistic to compare their haplotype patterns between them to search for evidence of genetic changes that are indicative of adaptation to their environment. We find evidence for adaptation at a critical gene that helps control physiological response to low-oxygen, one that has been the target of repeated convergent evolution across many species. We also find evidence for positive selection across a range of traits, including metabolic and neurological. This work helps to explain the evolutionary history of the rhesus macaque and furthers our understanding about the ways organisms genetically adapt to high-altitude environments.

evolutionary biology↗

bioRxiv2020

The bear bones: mosaic ancestry of Macaca arctoides explains divergent baculum morphology

Genital divergence is thought to contribute to reproductive barriers by establishing a "lock- and-key" mechanism for reproductive compatibility. One such example, Macaca arctoides, the bear macaque, has compensatory changes in both male and female genital morphology as compared to close relatives. Macaca arctoides also has a complex evolutionary history, having extensive introgression between the fascicularis and sinica macaque species groups. Here, phylogenetic relationships were analyzed via whole genome sequences from five species, including M. arctoides, and two species each from the putative parental species groups. This analysis revealed [~]3x more genomic regions supported placement in the sinica species group as compared to the fascicularis species group. Additionally, introgression analysis of the M. arctoides genome revealed it is a mosaic of recent polymorphisms shared with both species groups. To examine the evolution of their unique genital morphology further, the prevalence of candidate genes involved in genital morphology were compared against genome-wide outliers in various population genetic metrics, while accounting for background variation in recombination rate. This analysis identified 66 outlier genes, including several genes that influence baculum morphology in mice, which were of interest since the bear macaque has the longest primate baculum. The mean of several metrics was statistically different in the candidate genes as compared to the rest of the genome, suggesting that genes involved in genital morphology have increased divergence and decreased diversity beyond expectations. These results highlight how extensive introgression may have contributed to reproductive isolation and shaped the unique genital morphology in the bear macaque.

evolutionary biology↗