Biology subjects

Havens, J. L.

Publications and source records attributed to Havens, J. L..

3 recordsLinked to original sources

bioRxiv2023

The recency and geographical origins of the bat viruses ancestral to SARS-CoV and SARS-CoV-2

The emergence of SARS-CoV in 2002 and SARS-CoV-2 in 2019 has led to increased sampling of related sarbecoviruses circulating primarily in horseshoe bats. These viruses undergo frequent recombination and exhibit spatial structuring across Asia. Employing recombination-aware phylogenetic inference on bat sarbecoviruses, we find that the closest-inferred bat virus ancestors of SARS-CoV and SARS-CoV-2 existed just [~]1-3 years prior to their emergence in humans. Phylogeographic analyses examining the movement of related sarbecoviruses demonstrate that they traveled at similar rates to their horseshoe bat hosts and have been circulating for thousands of years in Asia. The closest-inferred bat virus ancestor of SARS-CoV likely circulated in western China, and that of SARS-CoV-2 likely circulated in a region comprising southwest China and northern Laos, both a substantial distance from where they emerged. This distance and recency indicate that the direct ancestors of SARS-CoV and SARS-CoV-2 could not have reached their respective sites of emergence via the bat reservoir alone. Our recombination-aware dating and phylogeographic analyses reveal a more accurate inference of evolutionary history than performing only whole-genome or single gene analyses. These results can guide future sampling efforts and demonstrate that viral genomic fragments extremely closely related to SARS-CoV and SARS-CoV-2 were circulating in horseshoe bats, confirming their importance as the reservoir species for SARS viruses.

evolutionary biology↗

bioRxiv2023

Chemical inhibition of bromodomain proteins in insect stage African trypanosomes perturbs silencing of the Variant Surface Glycoprotein repertoire and results in widespread changes in the transcriptome

The eukaryotic protozoan parasite Trypanosoma brucei, spp. is transmitted by the tsetse fly to both humans and animals, where it causes a fatal disease called African trypanosomiasis. While the parasite lacks canonical DNA sequence specific transcription factors, it does possess histones, histone modifications, and proteins that write, erase, and read histone marks. Chemical inhibition of chromatin interacting bromodomain proteins has previously been shown to perturb bloodstream specific trypanosome processes, including silencing of the Variant Surface Glycoprotein genes (VSGs) and immune evasion. Transcriptomic changes that occur in bromodomain inhibited bloodstream parasites mirror many of the changes that occur as parasites developmentally progress from the bloodstream to the insect stage. We performed RNA-seq timecourses to determine the effects of chemical bromodomain inhibition in insect stage parasites using the compound I-BET151. We found that treatment with I-BET151 causes large changes in the transcriptome of insect stage parasites, and also perturbs silencing of VSG genes. The transcriptomes of bromodomain inhibited parasites share some features with early metacyclic stage parasites in the fly salivary gland, implicating bromodomain proteins as important for regulating transcript levels for developmentally relevant genes. However, the downregulation of surface procyclin protein that typically accompanies developmental progression is absent in bromodomain inhibited insect stage parasites. We conclude that chemical modulation of bromodomain proteins causes widespread transcriptomic changes in multiple trypanosome life cycle stages. Understanding the gene regulatory processes that facilitate transcriptome remodeling in this highly diverged eukaryote may shed light on how these mechanisms evolved.

molecular biology↗

bioRxiv2022

Phylogeographic analysis reveals an ancient East African origin of the human herpes simplexvirus 2 dispersal out-of-Africa.

Human herpes simplex virus 2 (HSV-2) is a globally ubiquitous, slow evolving DNA virus. HSV-2 genomic diversity can be divided into two main groups: an African lineage and worldwide lineage. Competing hypotheses have been put forth to explain the history of HSV-2. HSV-2 may have originated in Africa and then followed the first wave of human migration out of Africa between 50-100 kya. Alternatively, HSV-2 may have migrated out of Africa via the trans-Atlantic slave trade within the last 150-500 years. The lack of HSV-2 genomes from West and Central Africa, combined with a lack of molecular clock signal in HSV-2 has precluded robust testing of these competing hypotheses. Here, we expand the geographic sampling of HSV-2 genomes in order to resolve the geography and timing of divergence events within HSV-2. We analyze 65 newly sequenced HSV-2 genomes collected from primarily West and Central Africa along with 330 previously published genomes sampled over a 47-year period. Evolutionary simulations confirm that the molecular clock in HSV-2 is too slow to be detected using available data. However, phylogeographic analysis indicates that all biologically plausible evolutionary rates would place the ancestor of the worldwide lineage in East Africa, arguing against the trans-Atlantic slave trade as the source of worldwide diversity. The best supported evolutionary rates between 4.2x10-8 and 5.6x10-8 substitutions/site/year suggest a most recent common ancestor for HSV-2 around 90-120 kya and initial dispersal around 21.9-29.3 kya. These dates suggest HSV-2 left Africa during subsequent waves of human migration out of East Africa.

evolutionary biology↗