Biology subjects

Wright, P. C.

Publications and source records attributed to Wright, P. C..

5 recordsLinked to original sources

bioRxiv2025

Genomic and microbiome data support a hypothesis of hybrid speciation in endangered brown lemurs

The gut microbiome is shaped by host ecology and evolution, but the relative influences of each remain unresolved in natural hybrid zones where species boundaries are permeable. We investigated these dynamics using a hybrid zone formed between two species of brown lemur in southeastern Madagascar, Eulemur rufifrons and E. cinereiceps. These hybrids occupy a novel ecological niche and were previously proposed as a hybrid species, though this had never been tested with genome-wide data. Here, we combined low-coverage host genomes derived from fecal DNA with 16S rRNA gut microbiome profiles across a 180-kilometer transect. Population genomic analyses recovered two population clusters connected by a hybrid zone biased towards E. rufifrons ancestry. Though our data did not support a hypothesis of hybrid speciation, the hybrid zone was dominated by later-generation crosses. Hybrid microbiomes were compositionally intermediate between parental species, but more closely resembled E. rufifrons, mirroring patterns of genomic ancestry. Microbiome beta diversity was significantly correlated with host genomic distance after accounting for geography and ecology. In contrast, predicted microbial functional profiles were broadly conserved across host taxa. Together, these findings demonstrate that phylosymbiosis can emerge in the face of interspecific gene flow, providing new insight into host-microbiome dynamics during the early stages of speciation.

evolutionary biology↗

bioRxiv2025

A primate model organism for cardiac arrhythmias identifies a magnesium transporter in pacemaker function

Cardiac arrhythmias afflict tens of millions of people, causing one-fifth of all deaths1. Although mouse models have aided understanding of some pacemaker genes and arrhythmias2,3, mice are not known to naturally acquire arrhythmias, and the substantial differences between mouse and human cardiac anatomy and physiology have limited their utility in preclinical studies and pharmacological testing2,4. To establish a primate genetic model organism for arrhythmias, we carried out an electrocardiographic (ECG) screen of over 350 lab and wild mouse lemurs (Microcebus spp.), an emerging model organism that is among the smallest, fastest-reproducing, and most abundant primates5. Twenty-two lemurs (6.2%) were identified with eight different naturally-occurring arrhythmias resembling human ECG pathologies (SSS, PACs, Afib, PVCs, NSVT, STD, iTWs, STE). Pedigree construction showed two were familial, premature atrial contractions (PACs)/atrial fibrillation (Afib) and sick sinus syndrome (SSS), an episodic bradycardia. Genome sequencing of the SSS pedigree mapped the disease locus to a 1.4 Mb interval on chromosome 7 and supported autosomal recessive Mendelian inheritance. The most appealing candidate gene in the interval was SLC41A2, a little studied magnesium transporter6,7. SLC41A2 is expressed in human iPSC-derived sinoatrial node cells (iSANC) and localizes to the sarcoplasmic reticulum. Although mouse SLC41A2 knockouts do not show a cardiac pacemaker phenotype8, CRISPR-mediated SLC41A2 knockout altered human iSANC magnesium dynamics and slowed their calcium transient firing rate. The results suggest SLC41A2 functions cell autonomously and primate-specifically in cardiac pacemaker cells, and that intracellular magnesium dynamics have a crucial but previously unappreciated role in setting pacemaker rate. Thus, mouse lemur is a valuable model for discovering new genes, molecules, and mechanisms of the primate pacemaker, and for identifying novel candidate genes and therapeutic targets for human arrhythmias. The approach can be used to elucidate other primate diseases and traits.

genetics↗

bioRxiv2024

De novo genome assembly for an endangered lemur using portable nanopore sequencing in rural Madagascar

As one of the most threatened mammalian taxa, lemurs of Madagascar are facing unprecedented anthropogenic pressures. To address conservation imperatives such as this, researchers have increasingly relied on conservation genomics to identify populations of particular concern. However, many of these genomic approaches necessitate high-quality genomes. While the advent of next generation sequencing technologies and the resulting reduction of associated costs have led to the proliferation of genomic data and high-quality reference genomes, global discrepancies in genomic sequencing capabilities often result in biological samples from biodiverse host countries being exported to facilities in the Global North, creating inequalities in access and training within genomic research. Here, we present the first reference genome for the endangered red-fronted brown lemur (Eulemur rufifrons) from sequencing efforts conducted entirely within the host country using portable Oxford Nanopore sequencing. Using an archived E. rufifrons specimen, we conducted long-read, nanopore sequencing at the Centre ValBio Research Station near Ranomafana National Park, in rural Madagascar, generating over 750 Gb of sequencing data from 10 MinION flow cells. Exclusively using this long-read data, we assembled 2.21 gigabase, 20,330-contig nuclear assembly with an N50 of 98.9 Mb and a 17,108 bp mitogenome. The nuclear assembly had 31x average coverage and was comparable in completeness to other primate reference genomes, with a 95.47% BUSCO completeness score for primate-specific genes. As the first reference genome for E. rufifrons and the only annotated genome available for the speciose Eulemur genus, this resource will prove vital for conservation genomic studies while our efforts exhibit the potential of this protocol to address research inequalities and build genomic capacity.

genomics↗

bioRxiv2023

Lemur gut microeukaryotic community variation is not associated with host phylogeny, diet, or habitat

Gut prokaryotic (GP) community variation is often associated with host evolutionary and ecological variables; whether these factors drive variation in other gut taxa remains largely untested. We present a one-to-one comparison of GP (16S rRNA metabarcoding) and microeukaryotic (GME) (18S rRNA metabarcoding) community patterning among 12 species of lemurs. Lemurs were sampled from dry forests and rainforests of southeastern Madagascar and display a range of phylogenetic and ecological diversity. We found that while lemur GPs vary with host taxonomy, diet, and habitat, GMEs have no association with these factors. As a mechanism, we suggest purifying selection purges microbes with negative and commensal associations, while positive selection promotes the persistence of beneficial microbes. It is therefore likely that a greater proportion of GMEs comprise taxa with commensal, transient, and parasitic symbioses compared with GPs, many of which are mutualists. Our study reveals different microbial taxa are shaped by unique selective pressures.

evolutionary biology↗

bioRxiv2017

Advancing A Science For Sustaining Health: Establishing A Model Health District in Madagascar

ObjectiveWe demonstrate a replicable model health district for Madagascar. The governments of many low-income countries have adopted health policies that follow international standards, and yet there are four hundred million people without basic access to primary care. Closing this global health delivery gap is typically framed as an issue of scale-up, accomplished primarily through integrating international donor funds with broad-based health system strengthening (HSS) efforts. However, there is no established process by which healthcare systems measure improvements at the point of service and how those, in turn, impact population health. There is no gold standard, equivalent to randomized trials of individual-level interventions, for health systems research. Here, we present a framework for a model district in Madagascar where national policies are implemented along with additional health system interventions to allow for bottom-up adaptation.\n\nSettingThe intervention takes place in a government district in Madagascar, which includes 1 district hospital, 20 primary care health centers, and a network of community health workers.\n\nInterventionThe program simultaneously strengthens the WHOs six building blocks of HSS at all levels of the health system within a government district and pioneers a data platform that includes 1) strengthening the districts health management information systems; 2) monitoring and evaluation dashboards; and 3) a longitudinal cohort demographic and health study of over 1,500 households, with a true baseline in intervention and comparison groups.\n\nConclusionThe integrated intervention and data platform allows for the evaluation of system output indicators as well as population-level impact indicators, such as mortality rates. It thus supports field-based implementation and policy research to fill the know-do gap, while providing the foundation for a new science of sustaining health.\n\nData Sharing StatementData can be made available upon request by emailing research@pivotworks.org.

epidemiology↗