Biology subjects

White, P. A.

Publications and source records attributed to White, P. A..

3 recordsLinked to original sources

bioRxiv2024

Dose-related Mutagenic and Clastogenic Effects of Benzofluoranthene in Mouse Somatic Tissues Detected by Duplex Sequencing and the Micronucleus Assay

Polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants that originate from the incomplete combustion of organic materials. We investigated the clastogenicity and mutagenicity of benzo[b]fluoranthene (BbF), one of 16 priority PAHs, in MutaMouse males after a 28-day oral exposure. BbF causes robust dose-dependent increases in micronucleus frequency in peripheral blood, indicative of chromosome damage. Duplex Sequencing (DS), an error-corrected sequencing technology, reveals that BbF induces dose-dependent increases in mutation frequencies in bone marrow (BM) and liver. Mutagenicity is increased in intergenic relative to genic regions, suggesting a role for transcription-coupled repair of BbF-induced DNA damage. At higher doses, the maximum mutagenic response to BbF is higher in liver, which has a lower mitotic index but higher metabolic capacity than BM; however, mutagenic potency is comparable between the two tissues. BbF induces primarily C:G>A:T mutations, followed by C:G>T:A and C:G>G:C, indicating that BbF metabolites mainly target guanines and cytosines. The mutation spectrum of BbF correlates with cancer mutational signatures associated with tobacco exposure, supporting its contribution to the carcinogenicity of combustion-derived PAHs in humans. Overall, BbFs mutagenic effects are similar to benzo[a]pyrene, a well-studied mutagenic PAH. Our work showcases the utility of DS for effective mutagenicity assessment of environmental pollutants. SynopsisWe used Duplex Sequencing to study the mutagenicity of benzo[b]fluoranthene across the mouse genome. Dose-dependent changes in mutation frequency and spectrum quantify its role in PAH-induced carcinogenicity.

pharmacology and toxicology↗

bioRxiv2020

Spatiotemporal Genetic Diversity of Lions

The Scramble for Africa in the late 1800s marked the beginning of increased human population growth in Africa. Here, we determined the genetic architecture of both historical and modern lions to identify changes in genetic diversity that occurred during this period of landscape and anthropogenic change. We surveyed microsatellite and mitochondrial genetic variation from 143 high-quality museum specimens of known provenance and combined them with data from recently published nuclear and mitochondrial studies. Analysis of variation at 9 microsatellites and 280 polymorphic mitogenome SNPs indicate the presence of male-mediated gene flow and recent isolation of local subpopulations, likely due to habitat fragmentation. Nuclear markers showed a significant decrease in genetic diversity from the historical (HE=0.833) to the modern (HE=0.796) populations, while mitochondrial genetic diversity was maintained (Hd=0.98 for both). While the historical population appears to have been panmictic based on nDNA data, hierarchical structure analysis identified four tiers of fine structure in modern populations, able to detect most sampling locations. Mitochondrial analyses identified 4 clusters: Southern, Mixed, Eastern, and Western; and were consistent between modern and historically sampled haplotypes. Within the last century, habitat fragmentation caused lion subpopulations to become more isolated as human expansion changed the African landscape. This resulted in an increase in fine-scale nuclear genetic structure and loss of genetic diversity as subpopulations became more differentiated, while mitochondrial structure and diversity was maintained over time.

genetics↗

bioRxiv2019

Whole genome sequencing and the application of a SNP panel reveal primary evolutionary lineages and genomic diversity in the lion (Panthera leo)

BackgroundPrevious phylogeographic studies of the lion (Panthera leo) have improved our insight into the distribution of genetic variation, as well as a revised taxonomy which now recognizes a northern (Panthera leo leo) and a southern (Panthera leo melanochaita) subspecies. However, existing whole range phylogeographic studies on lions either consist of very limited numbers of samples, or are focused on mitochondrial DNA and/or a limited set of microsatellites. The geographic extent of genetic lineages and their phylogenetic relationships remain uncertain, clouded by massive sampling gaps, sex-biased dispersal and incomplete lineage sorting. ResultsIn this study we present results of low depth whole genome sequencing and subsequent variant calling in ten lions sampled throughout the geographic range, resulting in the discovery of >150,000 Single Nucleotide Polymorphisms (SNPs). Phylogenetic analyses revealed the same basal split between northern and southern populations as well as four population clusters on a more local scale. Further, we designed a SNP panel, including 125 autosomal and 14 mitochondrial SNPs, which was tested on >200 lions from across their range. Results allow us to assign individuals to one of these four major clades (West & Central Africa, India, East Africa, or Southern Africa) and delineate these clades in more detail. ConclusionsThe results presented here, particularly the validated SNP panel, have important applications, not only for studying populations on a local geographic scale, but also for tracing samples of unknown origin for forensic purposes, and for guiding conservation management of ex situ populations. Thus, these genomic resources not only contribute to our understanding of the evolutionary history of the lion, but may also play a crucial role in conservation efforts aimed at protecting the species in its full diversity.

evolutionary biology↗