Evolutionary insights from wild vervet genomes

A new study reports genome-wide variation in 163 vervet monkeys from across their taxonomic and geographic ranges. The analysis suggests a complex history of admixture and identifies signals of repeated evolutionary selection, some of which may be linked to response to simian immunodeficiency virus.

As our closest genetic relatives, nonhuman primates (NHPs) have a critical role in comparative evolutionary studies and as models for human disease. Over the past decade, a range of NHP reference genomes have been assembled, vastly increasing understanding of primate genome dynamics and human-specific genomic features1. The availability of reference genomes also creates the possibility for population resequencing studies, but, so far, few such studies of wild NHP populations have been conducted, especially outside the great apes. In this issue, Magnus Nordborg and colleagues greatly expand the breadth of sequence data available for vervets2, a diverse genus of Old World monkeys that are important biomedical research models. They analyze the genomes of 163 individuals sampled from 11 countries across the native range of vervets in Africa as well as the Caribbean, where vervets were introduced in the seventeenth and eighteenth centuries. This represents all vervet taxa and is one of the largest genomic samples of wild NHPs thus far (Fig. 1).

Figure 1: Phylogeny and approximate numbers (orders of magnitude) of published genome sequences for apes and common NHP biomedical research models.
figure1

All taxa listed have at least a draft reference assembly. The vervet genomes, in red, are described in Svardal et al.2. The left side of the figure is adapted from ref. 1.

Resolving relationships

Vervets are generally divided into five or six taxa, but how these are related to each other and whether they should be considered as species or subspecies has been a matter of debate. Assessments of relationships by morphology, mitochondrial DNA and a small set of nuclear loci have come to different conclusions3,4. On the basis of genotypes at 61 million SNPs, Svardal et al.2 use pairwise genetic distances and principal-components analysis to offer the most thorough assessment of taxonomic relationships yet. On some aspects of the phylogeny, they find clarity: populations from the northern part of the vervet range in Africa cluster into three groups corresponding to the morphologically distinct sabaeus, aethiops and tantalus. Strong support places the West African sabaeus as an outgroup to the other taxa, in contrast to some previous findings4,5. They also find that the Caribbean populations are most closely related to the sabaeus group, corroborating historical records on their origin. Interestingly, genetic evidence suggests independent founder events in the Caribbean countries of Barbados and St. Kitts and Nevis.

In other ways, however, the taxonomic picture remains complicated. The taxa from the southern parts of the vervet range in Africa (cynosuros, hilgerti and pygerythrus) show high levels of shared variation with correlated allele frequencies, and genetic distances do not always reflect morphological classification. More generally, multiple methods for detecting historical hybridization find evidence for gene flow. The average pairwise divergence between taxa is 0.4%, which is higher than the divergence across most taxa designated as subspecies but lower than that for species-level comparisons. Although there is no evidence of recent interbreeding, all the vervet taxa show genomic signatures of historical admixture. This finding adds to a growing number of observations of gene flow between closely related primates6.

Living with SIV

Vervets are natural hosts of simian immunodeficiency viruses (SIVs), which are closely related to HIV. Like other natural SIV hosts, vervets do not develop AIDS, and it has been hypothesized that host and virus are in a coevolutionary arms race that has led to tolerance to infection. How might genes that have been under selection due to SIV be identified? Reasoning that the arms race scenario would lead to different variants favored in different populations, Svardal et al.2 chose to look for selection using XP-CLR, a test that compares populations to identify loci with unusually large allele frequency differences across linked variants, indicative of population-specific selection. They then combined XP-CLR results from pairwise taxon comparisons into a single score that is a measure of evidence for repeated population-specific selection. Indeed, the Gene Ontology (GO) categories enriched for high selection scores included several related to viral response.

To connect the selection scores more directly with response to SIV, Svardal et al.2 turned to a published data set of gene expression measured throughout experimental SIV infection of vervets and rhesus macaques7. Rhesus macaques belong to another Old World monkey genus and are not natural SIV hosts; they do develop AIDS-like symptoms upon infection. Intriguingly, Svardal et al.2 found an enrichment of high selection scores in genes that change expression in vervets but not macaques upon infection. This suggests that selection has acted on genes that are involved in responding to SIV infection specifically in vervets. The selection scores are particularly enriched for genes whose expression changes at 6 or 115 days after infection, pointing to particular time points that might be important in vervet-specific tolerance to SIV. This kind of integration between patterns of genomic variation in wild populations and laboratory-based phenotyping is a promising strategy for deciphering the phenotypes associated with selection signals. Specific candidate genes and pathways can then be followed up back in the laboratory.

Both field and laboratory

The study by Svardal et al.2 greatly expands the genomic data available for wild vervets and provides new insights into their evolutionary histories. Another exciting development in vervet genomics is the application of high-throughput sequencing to research animals, which will allow for a range of genotype-informed phenotypic studies under controlled conditions. In 2015, sequence data for 721 individuals from the Vervet Research Colony in the United States were reported8, and, on page 1714 of this issue, Nelson Freimer and colleagues present a multitissue expression quantitative trait locus (eQTL) study in a subset of these sequenced vervets9. Although eQTL studies are now commonplace in humans, they have only recently begun to be applied to NHPs. As illustrated by the two studies in this issue, genomic analysis of NHPs offers a complementary approach to the work being carried out in humans to understand the evolution and genetic architecture of complex phenotypes. As the accessibility of sequencing continues to increase, genotype–phenotype analyses in NHPs are likely to bring even more insights.

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Correspondence to Ellen M Leffler.

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Leffler, E. Evolutionary insights from wild vervet genomes. Nat Genet 49, 1671–1672 (2017). https://doi.org/10.1038/ng.3992

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