A genome-wide survey of segmental duplications that mediate common human genetic variation of chromosomal architecture.

Recent studies have identified a small number of genomic rearrangements that occur frequently in the general population. Bioinformatics tools are now available for systematic genome-wide surveys of higher-order structures predisposing to such common variations in genomic architecture. Segmental duplications (SDs) constitute up to 5 per cent of the genome and play an important role in generating additional rearrangements and in disease aetiology. We conducted a genome-wide database search for a form of SD, palindromic segmental duplications (PSDs), which consist of paired, inverted duplications, and which predispose to inversions, duplications and deletions. The survey was complemented by a search for SDs in tandem orientation (TSDs) that can mediate duplications and deletions but not inversions. We found more than 230 distinct loci with higher-order genomic structure that can mediate genomic variation, of these about 180 contained a PSD. A number of these sites were previously identified as harbouring common inversions or as being associated with specific genomic diseases characterised by duplication, deletions or inversions. Most of the regions, however, were previously unidentified; their characterisation should identify further common rearrangements and may indicate localisations for additional genomic disorders. The widespread distribution of complex chromosomal architecture suggests a potentially high degree of plasticity of the human genome and could uncover another level of genetic variation within human populations

The complex genetic basis of simple behavior

Genetic approaches to dissecting complex traits in animal models increasingly use transcript levels as a molecular phenotype and as validation for predictions of gene function. A recent study in BMC Biology using these approaches shows the complexity of the genetic contribution to aggressive behavior in Drosophila

Comparative growth and static allometry in the genus Chlorocebus

Characterizing variation in growth across populations is critical to understanding multiple aspects of development in primates, including within-taxon developmental plasticity and the evolution of life history patterns. Growth in wild primates has often been reported and directly compared across larger taxonomic groups and within social groups, but comparisons are rarely investigated across widely dispersed populations of a single taxon. With the Vervet Phenome-Genome Project and the International Vervet Research Consortium, we trapped 936 vervet monkeys of all ages representing three populations (Kenyan pygerythrus, South African pygerythrus, and sabaeus from St. Kitts & Nevis). We gathered 10 different body measurements from each including mass, body breadth and length, segmental limb lengths, and chest circumference. To gain a better understanding of how ontogenetic patterns vary in these populations, we calculated bivariate allometry coefficients, derived using PCA on log-transformed and z-standardized trait values, and compared them to isometric vector coefficients. Within all population samples, around weaning age most traits showed a negative allometric relationship to body length. As each population ages, however, distinct patterns emerge, showing population differences in onset and intensity of growth among traits. In concordance with other analyses on growth in these populations, our results suggest that there exist relative differences in patterns of growth between Chlorocebus populations, further suggesting selection for unique developmental pathways in each

The genome of the vervet (Chlorocebus aethiops sabaeus)

Warren, Wesley C. et al.We describe a genome reference of the African green monkey or vervet (Chlorocebus aethiops). This member of the Old World monkey (OWM) superfamily is uniquely valuable for genetic investigations of simian immunodeficiency virus (SIV), for which it is the most abundant natural host species, and of a wide range of health-related phenotypes assessed in Caribbean vervets (C. a. sabaeus), whose numbers have expanded dramatically since Europeans introduced small numbers of their ancestors from West Africa during the colonial era. We use the reference to characterize the genomic relationship between vervets and other primates, the intra-generic phylogeny of vervet subspecies, and genome-wide structural variations of a pedigreed C. a. sabaeus population. Through comparative analyses with human and rhesus macaque, we characterize at high resolution the unique chromosomal fission events that differentiate the vervets and their close relatives from most other catarrhine primates, in whom karyotype is highly conserved. We also provide a summary of transposable elements and contrast these with the rhesus macaque and human. Analysis of sequenced genomes representing each of the main vervet subspecies supports previously hypothesized relationships between these populations, which range across most of sub-Saharan Africa, while uncovering high levels of genetic diversity within each. Sequence-based analyses of major histocompatibility complex (MHC) polymorphisms reveal extremely low diversity in Caribbean C. a. sabaeus vervets, compared to vervets from putatively ancestral West African regions. In the C. a. sabaeus research population, we discover the first structural variations that are, in some cases, predicted to have a deleterious effect; future studies will determine the phenotypic impact of these variations.Funding to R.K.W. was provided by NIH-NHGRI grant 5U54HG00307907. Support for the Vervet Research Colony was provided by NIH grant RR019963/OD010965 to J.R.K. Funding to N.B.F. was provided by NIH grants R01RR016300 and R01OD010980. The French National Agency for Research on AIDS and Viral Hepatitis (ANRS) provided funding to M.C.M.-T. Funding to M.R. and R.S. was provided by the Ministero della Universita’ e della Ricerca. Funding to K.D. was provided by Genome Canada and Genome Quebec. B.A. and R.N. acknowledge support from the Wellcome Trust (grant number WT095908) and the European Molecular Biology Laboratory.Peer reviewe

The static allometry of sexual and non-sexual traits in vervet monkeys

Sexual traits vary tremendously in static allometry. This variation may be explained in part by body size-related differences in the strength of selection. We tested this hypothesis in two populations of vervet monkeys, using estimates of the level of condition dependence for different morphological traits as a proxy for body size-related variation in the strength of selection. In support of the hypothesis, we found that the steepness of allometric slopes increased with the level of condition dependence. One trait of particular interest, the penis, had shallow allometric slopes and low levels of condition dependence, in agreement with one of the most consistent patterns yet detected in the study of allometry, namely that of genitalia exhibiting shallow allometries.This research was supported by NIH grant R01RR0163009

Anatomic brain asymmetry in vervet monkeys.

Asymmetry is a prominent feature of human brains with important functional consequences. Many asymmetric traits show population bias, but little is known about the genetic and environmental sources contributing to inter-individual variance. Anatomic asymmetry has been observed in Old World monkeys, but the evidence for the direction and extent of asymmetry is equivocal and only one study has estimated the genetic contributions to inter-individual variance. In this study we characterize a range of qualitative and quantitative asymmetry measures in structural brain MRIs acquired from an extended pedigree of Old World vervet monkeys (n = 357), and implement variance component methods to estimate the proportion of trait variance attributable to genetic and environmental sources. Four of six asymmetry measures show pedigree-level bias and one of the traits has a significant heritability estimate of about 30%. We also found that environmental variables more significantly influence the width of the right compared to the left prefrontal lobe

Morphological variation in the genus Chlorocebus: Ecogeographic and anthropogenically mediated variation in body mass, postcranial morphology, and growth

Objectives Direct comparative work in morphology and growth on widely dispersed wild primate taxa is rarely accomplished, yet critical to understanding ecogeographic variation, plastic local variation in response to human impacts, and variation in patterns of growth and sexual dimorphism. We investigated population variation in morphology and growth in response to geographic variables (i.e., latitude, altitude), climatic variables (i.e., temperature and rainfall), and human impacts in the vervet monkey (Chlorocebus spp.). Methods We trapped over 1,600 wild vervets from across Sub‐Saharan Africa and the Caribbean, and compared measurements of body mass, body length, and relative thigh, leg, and foot length in four well‐represented geographic samples: Ethiopia, Kenya, South Africa, and St. Kitts & Nevis. Results We found significant variation in body mass and length consistent with Bergmann\u27s Rule in adult females, and in adult males when excluding the St. Kitts & Nevis population, which was more sexually dimorphic. Contrary to Rensch\u27s Rule, although the South African population had the largest average body size, it was the least dimorphic. There was significant, although very small, variation in all limb segments in support for Allen\u27s Rule. Females in high human impact areas were heavier than those with moderate exposures, while those in low human impact areas were lighter; human impacts had no effect on males. Conclusions Vervet monkeys appear to have adapted to local climate as predicted by Bergmann\u27s and, less consistently, Allen\u27s Rule, while also responding in predicted ways to human impacts. To better understand deviations from predicted patterns will require further comparative work in vervets

Seroprevalence of Zika virus in wild African green monkeys and baboons

ABSTRACT Zika virus (ZIKV) has recently spread through the Americas and has been associated with a range of health effects, including birth defects in children born to women infected during pregnancy. Although the natural reservoir of ZIKV remains poorly defined, the virus was first identified in a captive “sentinel” macaque monkey in Africa in 1947. However, the virus has not been reported in humans or nonhuman primates (NHPs) in Africa outside Gabon in over a decade. Here, we examine ZIKV infection in 239 wild baboons and African green monkeys from South Africa, the Gambia, Tanzania, and Zambia using combinations of unbiased deep sequencing, quantitative reverse transcription-PCR (qRT-PCR), and an antibody capture assay that we optimized using serum collected from captive macaque monkeys exposed to ZIKV, dengue virus, and yellow fever virus. While we did not find evidence of active ZIKV infection in wild NHPs in Africa, we found variable ZIKV seropositivity of up to 16% in some of the NHP populations sampled. We anticipate that these results and the methodology described within will help in continued efforts to determine the prevalence, natural reservoir, and transmission dynamics of ZIKV in Africa and elsewhere. IMPORTANCE Zika virus (ZIKV) is a mosquito-borne virus originally discovered in a captive monkey living in the Zika Forest of Uganda, Africa, in 1947. Recently, an outbreak in South America has shown that ZIKV infection can cause myriad health effects, including birth defects in the children of women infected during pregnancy. Here, we sought to investigate ZIKV infection in wild African primates to better understand its emergence and spread, looking for evidence of active or prior infection. Our results suggest that up to 16% of some populations of nonhuman primate were, at some point, exposed to ZIKV. We anticipate that this study will be useful for future studies that examine the spread of infections from wild animals to humans in general and those studying ZIKV in primates in particular. Podcast: A podcast concerning this article is available