Biology subjects

Foley, N. M.

Publications and source records attributed to Foley, N. M..

6 recordsLinked to original sources

bioRxiv2026

Comparative Genomics Reveals the Ancestral Recombination Landscape of Placental Mammals

Meiotic recombination is a crucial biological process that ensures proper chromosomal pairing and promotes adaptation. In placental mammals, recombination rates vary widely across species, populations, sexes, individuals, and chromosomes. While the placental X chromosome shows remarkable conservation of both gene order and the recombination landscape across deep evolutionary history, it is unknown whether similar levels of autosomal conservation persist despite extensive chromosomal evolution. Here, we reconstructed an ancestral placental mammal karyotype from chromosome-level assemblies, using slow rates of karyotypic evolution, and inferred an ancestral autosomal recombination map. Analysis of phylogenetic branch lengths and PhyloP-based scores of evolutionary constraint reveals that conserved autosomal regions with low recombination rates have evolved under stronger purifying selection, whereas regions with conserved high recombination rates are less constrained and freer to evolve. Ancestral autosomal regions with low recombination rates were enriched for pathways and GO terms related to cellular function, whereas ancestral regions with high recombination rates were enriched for regulation and some immune-related systems. Tracking the fate of these conserved ancestral recombination hotspots and coldspots across 13 mammal lineages with variable rates of karyotype evolution revealed the retention of autosomal AHRs, but the absence of autosomal ALR conservation. Collectively, our findings reveal variable levels of evolutionary constraint at meiotic recombination in relation to karyotypic evolution, providing new insights into how natural selection influences the evolution of chromosomal organization.

genomics↗

bioRxiv2025

Mutation rate estimate and population genomic analysis reveals decline of koalas prior to human arrival

The koala (Phascolarctos cinereus), an iconic Australian marsupial, has experienced substantial historical and contemporary population declines. Identifying the drivers of these declines has been hindered by limited genomic data and by uncertainty regarding the koala mutation rate. Here, we provide the first direct estimate of the koala mutation rate, based on four parent-offspring trios, yielding a mean of 6.12x10{square}{square} mutations per base pair per generation (95% confidence interval: 5.03-7.45x10{square}{square}). Using this estimate of the rate, we reconstructed the demographic history of koalas using 458 whole-genome sequences sampled across their entire range. Our results refine the estimated timing of past changes in population size, suggesting a large decline beginning [~]100 kya, before the arrival of modern humans in Australia. The koala population then split into five genetic populations 6-30 kya, which are now spread across >3500 km on the east coast of Australia. We also use the koala mutation rate to infer recombination maps for each population, confirming lower recombination rates in marsupials than in eutherian mammals. These findings provide critical insights into the evolutionary history of koalas, while highlighting the impact of using species-specific evolutionary rates in the inference of demographic histories and recombination landscapes. Our estimates of the genome-wide mutation rate and population-specific recombination maps for koalas provide valuable resources for future evolutionary and conservation analyses of marsupials.

evolutionary biology↗

bioRxiv2023

Evolutionary constraint and innovation across hundreds of placental mammals

Evolutionary constraint and acceleration are powerful, cell-type agnostic measures of functional importance. Previous studies in mammals were limited by species number and reliance on human-referenced alignments. We explore the evolution of placental mammals, including humans, through reference-free whole-genome alignment of 240 species and protein-coding alignments for 428 species. We estimate 10.7% of the human genome is evolutionarily constrained. We resolve constraint to single nucleotides, pinpointing functional positions, and refine and expand by over seven-fold the catalog of ultraconserved elements. Overall, 48.5% of constrained bases are as yet unannotated, suggesting yet-to-be-discovered functional importance. Using species-level phenotypes and an updated phylogeny, we associate coding and regulatory variation with olfaction and hibernation. Focusing on biodiversity conservation, we identify genomic metrics that predict species at risk of extinction.

genomics↗

bioRxiv2022

A genomic timescale for placental mammal evolution

The precise pattern and timing of speciation events that gave rise to all living placental mammals remain controversial. We provide a comprehensive phylogenetic analysis of genetic variation across an alignment of 241 placental mammal genome assemblies, addressing prior concerns regarding limited genomic sampling across species. We compared neutral genome-wide phylogenomic signal using concatenation and coalescent-based approaches, interrogated phylogenetic variation across chromosomes and analyzed extensive catalogs of structural variants. Interordinal relationships exhibit relatively low rates of phylogenomic conflict across diverse datasets and analytical methods. Conversely, X-chromosome versus autosome conflicts characterize multiple independent clades that radiated during the Cenozoic. Genomic timetrees reveal an accumulation of cladogenic events before and immediately following the KPg boundary implying important roles for Cretaceous continental vicariance and the KPg extinction in the placental radiation. One-Sentence SummaryA comprehensive whole genome phylogeny of extant placental mammals reveals timing and patterns of ordinal diversification.

evolutionary biology↗

bioRxiv2022

Tree House Explorer: A Novel Genome Browser for Phylogenomics

Tree House Explorer (THEx) is a genome browser that integrates phylogenomic data and genomic annotations into a single interactive platform for combined analysis. THEx allows users to visualize genome-wide variation in evolutionary histories and genetic divergence on a chromosome-by-chromosome basis, with continuous sliding window comparisons to gene annotations, recombination rates, and other user-specified, highly customizable feature annotations. THEx provides a new platform for interactive phylogenomic data visualization to analyze and interpret the diverse evolutionary histories woven throughout genomes. Hosted on Conda, THEx integrates seamlessly into new or pre-existing workflows.

bioinformatics↗

bioRxiv2017

Population level mitogenomics of the long-lived Greater Mouse-eared bat, Myotis myotis, reveals dynamic heteroplasmy and challenges the Free Radical Theory of Ageing

BackgroundBats are the only mammals capable of true, powered flight, which drives an extremely high metabolic rate. The \"Free Radical Theory of Ageing\" (FTRA) posits that a high metabolic rate leads to mitochondrial heteroplasmy and the progressive ageing phenotype. Contrary to this, bats are the longest lived order of mammals despite their small size and high metabolic rate. To investigate if bats exhibit increased mitochondrial heteroplasmy with age as predicted by the FRTA, we performed targeted, deep sequencing of mitogenomes and measured point heteroplasmy in wild, long lived Myotis myotis as they age.\n\nResultsIn total, blood was sampled from 195 individuals, aged between <1 and at 6+ years old, and whole mitochondria were sequenced, with a subset sampled over multiple years. The majority of heteroplasmies, 77.6%, were at a frequency below 5%. Oxidative mutations were not the primary source of heteroplasmies and present in only a small number of individuals, likely representing local oxidative stress events. There was a significant positive correlation between age and heteroplasmy, with a rate of increase of 0.13 sites per year. Longitudinal data from recaptured individuals show heteroplasmy is dynamic, and does not increase uniformly over time.\n\nConclusionsWe show that bats do not suffer from the predicted, inevitable increase in heteroplasmy which underscores the FRTA. Most heteroplasmies were at low frequency and are primarily transitions. Heteroplasmy increased with age, however how this contributes to ageing is unclear, as heteroplasmy was dynamic, questioning its presumed role as a primary driver of ageing.

genomics↗