Jasinska, A. | Search bioRxiv

bioRxiv2019

The burden of deleterious variants in a non-human primate biomedical model

Genome sequencing studies of nonhuman primate (NHP) pedigree and population samples are discovering variants on a large and rapidly growing scale. These studies are increasing the utility of several NHP species as model systems for human disease. In particular, by identifying homozygous protein truncating variants (hPTVs) in genes hypothesized to play a role in causing human diseases, it may be possible to elucidate mechanisms for the phenotypic impact of such variants through investigations that are infeasible in humans. The Caribbean vervet (Chlorocebus aethiops sabaeus) is uniquely valuable for this purpose, as the dramatic expansion of its population following severe bottlenecks has enabled PTVs that passed through the bottleneck to attain a relatively high frequency. Using whole genome sequence (WGS) data from 719 monkeys of the Vervet Research Colony (VRC) extended pedigree, we found 2,802 protein-truncating alleles in 1,747 protein-coding genes present in homozygous state in at least one monkey. Polymorphic sites for 923 SNV hPTVs were also observed in natural Caribbean populations from which the VRC descends. The vervet genome browser (VGB) includes information on these PTVs, together with a catalog of phenotypes and biological samples available for monkeys who carry them. We describe initial explorations of the possible impact of vervet PTVs on early infant mortality.

genetics↗

bioRxiv2016

Ancient hybridization and strong adaptation to viruses across African vervet monkey populations

Vervet monkeys (genus Chlorocebus, also known as African green monkeys), are highly abundant in savannahs and riverine forests throughout sub-Saharan Africa. They are amongst the most widely distributed nonhuman primates, show considerable phenotypic diversity, and have long been an important biomedical model for a variety of human diseases1 and in vaccine research2-4. They are particularly interesting for HIV/AIDS research as they are the most abundant natural hosts of simian immunodeficiency virus (SIV), a close relative of HIV. Here we present the first genome-wide survey of polymorphism in vervets, using sequencing data from 163 individuals sampled from across Africa and the Caribbean islands where vervets were introduced during the colonial era. We find high diversity, within and between taxa, and clear evidence that taxonomic divergence was reticulate rather than following a simple branching pattern. A scan for diversifying selection across vervet taxa yields gene enrichments much stronger than in similar studies on humans5. In particular, we report strong and highly polygenic selection signals affecting viral processes -- in line with recent evidence that proposes a driving role for viruses in protein evolution in mammals6. Furthermore, selection scores are highly elevated in genes whose human orthologs interact with HIV, and in genes that show a response to experimental SIV infection in vervet monkeys but not in rhesus macaques, suggesting that part of the signal reflects taxon-specific adaptation to SIV. Intriguingly, rather than affecting genes with antiviral and inflammatory-related functions7, selection in vervets appears to have primarily targeted genes involved in the transcriptional regulation of viruses, and in particular those that are harmful only under immunodeficiency, suggesting adaptation to living with SIV rather than defense against infection.

evolutionary biology↗