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Bergey, C. M.

Publications and source records attributed to Bergey, C. M..

15 recordsLinked to original sources

Genetically-based sperm discrimination in the vaginal tract of a primate species

Females influence offspring paternity through diverse pre- and post-copulatory mechanisms. Sperm discrimination--the differential physiological response to ejaculates based on male or sperm characteristics--can bias fertilization outcomes, but in vivo evidence of this process in large-bodied mammals is lacking. Here, we tested whether two aspects of female physiology that affect sperm survival-vaginal immune response and pH-are modulated by male genetic makeup in a nonhuman primate. We observed post-copulatory differences in vaginal gene expression and pH, with the strongest immune responses and largest pH decreases, harmful to sperm, exhibited by females mating with genetically similar males. These findings support genetically based post-copulatory mate discrimination in primates, shedding light on the interaction between male gametes and the female reproductive tract and potentially explaining variation in conception probability.

evolutionary biology↗

De novo genome assembly for an endangered lemur using portable nanopore sequencing in rural Madagascar

As one of the most threatened mammalian taxa, lemurs of Madagascar are facing unprecedented anthropogenic pressures. To address conservation imperatives such as this, researchers have increasingly relied on conservation genomics to identify populations of particular concern. However, many of these genomic approaches necessitate high-quality genomes. While the advent of next generation sequencing technologies and the resulting reduction of associated costs have led to the proliferation of genomic data and high-quality reference genomes, global discrepancies in genomic sequencing capabilities often result in biological samples from biodiverse host countries being exported to facilities in the Global North, creating inequalities in access and training within genomic research. Here, we present the first reference genome for the endangered red-fronted brown lemur (Eulemur rufifrons) from sequencing efforts conducted entirely within the host country using portable Oxford Nanopore sequencing. Using an archived E. rufifrons specimen, we conducted long-read, nanopore sequencing at the Centre ValBio Research Station near Ranomafana National Park, in rural Madagascar, generating over 750 Gb of sequencing data from 10 MinION flow cells. Exclusively using this long-read data, we assembled 2.21 gigabase, 20,330-contig nuclear assembly with an N50 of 98.9 Mb and a 17,108 bp mitogenome. The nuclear assembly had 31x average coverage and was comparable in completeness to other primate reference genomes, with a 95.47% BUSCO completeness score for primate-specific genes. As the first reference genome for E. rufifrons and the only annotated genome available for the speciose Eulemur genus, this resource will prove vital for conservation genomic studies while our efforts exhibit the potential of this protocol to address research inequalities and build genomic capacity.

genomics↗

Hyper-specialized bamboo lemurs possess a reduced suite of xenobiotic-metabolizing cytochrome P450 genes.

Subfamilies of cytochrome P450 proteins have been strongly linked to the metabolism of physiologically disruptive compounds such as alkaloids, terpenoids, and other xenobiotics. Consistent with this function, these genes have adaptively evolved in response to environmental pressures exerted on animals, such as herbivores, that consume elevated amounts of toxic xenobiotics or plant secondary metabolites (PSMs). Theory on evolutionary tradeoffs predicts that highly specialized herbivores should exhibit a relatively narrow toolkit of adaptations to accommodate the concomitantly narrow arrays of PSMs in their diets. The bamboo lemurs of Madagascar (genera Prolemur and Hapalemur) represent an interesting test case for this theory because of their dietary hyper-specialization, as these lemurs consume bamboo and grasses at rates otherwise unseen in the order Primates. To test whether the hyper-specialized folivory of these primates is reflected in a similarly specialized and narrow P450 gene suite, we assembled a dataset of confidently assembled CYP1-3 genes for two species of bamboo lemur as well as additional lemur species. We tested the predictions that bamboo lemurs would exhibit, first, greater rates of gene loss for xenobiotic-metabolizing P450s and, second, relaxed selection on xenobiotic-metabolizing P450 subfamilies relative to lemurs without such dietary hyper-specialization. We found support for the first prediction, related to gene loss, in the CYP2B, CYP2C, CYP2D, CYP2J, and CYP3A subfamilies, all of which encode xenobiotic metabolizers. We additionally inferred relaxation of selection for the CYP2F and CYP2J subfamilies. The evolution of the P450 genes in bamboo lemurs provides support for the evolutionary tradeoff hypothesis, and we further hypothesize that, rather than adapting to a general array of PSMs, bamboo lemurs have instead adapted to the primary toxin in their diet, the highly potent poison cyanide. HighlightsO_LISome of the most specialized diets among primates are those of bamboo lemurs. C_LIO_LIBamboo lemurs have fewer xenobiotic-metabolizing P450 genes than other lemurs. C_LIO_LINatural selection has relaxed on the CYP2F and CYP2J subfamilies in bamboo lemurs. C_LI

evolutionary biology↗

Genomic signatures of adaptation in native lizards exposed to human-introduced fire ants

Understanding the process of genetic adaptation in response to human-mediated ecological change will help elucidate the eco-evolutionary impacts of human activity. Red fire ants (Solenopsis invicta) spread across Southeastern USA since their accidental introduction via Port Mobile, Alabama in the 1930s, serving today as both novel venomous predator and novel toxic prey to native eastern fence lizards (Sceloporus undulatus). To identify potential signatures of genetic adaptation in lizards to invasive fire ants, we generated whole genome sequencing data from 420 native fence lizards sampled across three populations, two of which had not been invaded by fire ants (in Tennessee and Arkansas) and one which had been invaded for [~]70 years (Alabama). We detected signatures of positive selection exclusive to the exposed Alabama population for genetic variants overlapping genes related to the membrane attack complex of the complement immune system, growth factor pathways, and morphological development. Prior work identified a relationship between increased lizard survival of fire ant attack and longer hind limbs, which lizards use to remove ants from their bodies. Furthermore, we conducted a genome-wide association study with 381 Alabama lizards to identify 24 hind limb length-associated genetic loci. For two loci, positive-effect alleles occur in high frequency and overlap genomic regions that are highly differentiated from the populations naive to fire ants. Collectively, these findings represent plausible genetic adaptations in response to fire ant invasion, whereby morphological differentiation may increase survival against swarming ants and altered immune responses may allow the exploitation of a novel, toxic food resource. Significance statementHuman activity can force interactions between species from distinct ecological backgrounds. These interactions can consequently impose novel selective pressures on endemic populations via predation or disruption of ecological niches through community-wide effects. While some endemic taxa have been able to adapt biologically to these disruptions, we do not have a full understanding of the underlying genetic processes that may allow it. Here we identify genomic signatures of recent adaptation nearby genes involved in morphological and immunological processes in native fence lizards that are consistent with pressures imposed by the venomous, predatory fire ants introduced by humans. These signatures are largely absent from lizard populations that are naive to fire ants.

evolutionary biology↗

Genome-wide coancestry reveals details of ancient and recent male-driven reticulation in baboons

Baboons (genus Papio) are a morphologically and behaviorally diverse clade of catarrhine monkeys that have experienced hybridization between phenotypically and genetically distinct phylogenetic species. We used high coverage whole genome sequences from 225 wild baboons representing 19 geographic localities to investigate population genomics and inter-species gene flow. Our analyses provide an expanded picture of evolutionary reticulation among species and reveal novel patterns of population structure within and among species, including differential admixture among conspecific populations. We describe the first example of a baboon population with a genetic composition that is derived from three distinct lineages. The results reveal processes, both ancient and recent, that produced the observed mismatch between phylogenetic relationships based on matrilineal, patrilineal, and biparental inheritance. We also identified several candidate genes that may contribute to species-specific phenotypes. One-Sentence SummaryGenomic data for 225 baboons reveal novel sites of inter-species gene flow and local effects due to differences in admixture.

evolutionary biology↗

Gene expression of macaques infected with malaria species of zoonotic concern

A multitude of malaria species (genus Plasmodium) infects primates. Due to their public health importance, the human-infective species have garnered the most focus, but increased knowledge of non-human primate malaria species is warranted to improve our evolutionary understanding of host-parasite interactions. Additionally, the broad host tropism of some primate malaria parasites and their realized or theorized zoonotic potential add urgency to understanding of primate-parasite interactions. Here, we use comparative transcriptomics to understand the rhesus macaque (Macaca mulatta) response to two malaria parasites used as analogues to human-infective species of differing severity and which may represent emerging zoonotic threats: P. coatneyi, comparable to human-infective P. falciparum, and P. cynomolgi, comparable to human-infective P. vivax. We first validate our transcriptomics-based proxy of parasite load through comparison to gold-standard microscopy-based measures. We then find that malaria-associated host genes have functional links to immune system regulation and blood cells. Host genes with differing expression by malaria species were more likely to be involved in brain-linked functions, perhaps due to the differential central nervous system involvement of the two parasite species. Such comparative work on primate malaria species may help elucidate the essential and species-specific molecular mechanisms that underlie differing clinical presentations and zoonotic risk.

systems biology↗

High-altitude adaptation and incipient speciation in geladas

Survival at high altitude requires adapting to extreme conditions such as environmental hypoxia. To understand high-altitude adaptations in a primate, we assembled the genome of the gelada (Theropithecus gelada), an endemic Ethiopian monkey, and complemented it with population resequencing, hematological, and morphometric data. Unexpectedly, we identified a novel karyotype that may contribute to reproductive isolation between gelada populations. We also identified genomic elements including protein-coding sequences and gene families that exhibit accelerated changes in geladas and may contribute to high-altitude adaptation. Our findings lend insight into mechanisms of speciation and adaptation while providing promising avenues for functional hypoxia research.

genomics↗

Novel genome assemblies and Evolutionary Dynamics of North American Anopheles mosquitoes

Anopheles mosquitoes are the principal vectors for malaria and lymphatic filariasis, and evidence for arboviral transmission under laboratory and natural contexts has been demonstrated. Vector management approaches require an understanding of the ecological, epidemiological, and biological context of the species in question, and increased interest in gene drive systems for vector control applications has resulted in an increased need for genome assemblies from understudied mosquito species. While the genomes for many Anopheles species have been sequenced, North American Anopheles taxa have been neglected. In this study we present novel genome assemblies for the North American species An. crucians, An. freeborni, An. albimanus, and An. quadrimaculatus, and examine the evolutionary relationship between these species. We identified 790 shared single copy orthologs between the newly sequenced genomes and created a phylogeny using 673 of the orthologs, identifying 525 orthologs with evidence for positive selection on at least one branch of the phylogeny. Gene ontology terms such as calcium ion signaling, histone binding, and protein acetylation were identified as being biased in the set of selected genes. These novel genome sequences will be useful in developing our understanding of the diverse biological traits that drive vectorial capacity in anophelines.

genomics↗

Immunogenetic response to a malaria-like parasite in a wild primate

Malaria is infamous for the massive toll it exacts on human life and health. In the face of this intense selection, many human populations have evolved mechanisms that confer some resistance to the disease, such as sickle-cell hemoglobin or the Duffy null blood group. Less understood are adaptations in other vertebrate hosts, many of which have a longer history of co-evolution with malaria parasites. By comparing malaria resistance adaptations across host species, we can gain fundamental insight into host-parasite co-evolution. In particular, understanding the mechanisms by which non-human primate immune systems combat malaria may be fruitful in uncovering transferable therapeutic targets for humans. However, most research on primate response to malaria has focused on a single or few loci, typically in experimentally-infected captive primates. Here, we report the first transcriptomic study of a wild primate response to a malaria-like parasite, investigating gene expression response of red colobus monkeys (Piliocolobus tephrosceles) to natural infection with the malaria-like parasite, Hepatocystis. We identified colobus genes with expression strongly correlated with parasitemia, including many implicated in human malaria and suggestive of common genetic architecture of disease response. For instance, the expression of ACKR1 (alias DARC) gene, previously linked to resistance in humans, was found to be positively correlated with parasitemia. Other similarities to human parasite response include induction of changes in immune cell type composition and, potentially, increased extramedullary hematopoiesis and altered biosynthesis of neutral lipids. Our results illustrate the utility of comparative immunogenetic investigation of malaria response in primates. Such inter-specific comparisons of transcriptional response to pathogens afford a unique opportunity to compare and contrast the adaptive genetic architecture of disease resistance, which may lead to the identification of novel intervention targets to improve human health. Author SummaryThe co-evolutionary arms race between humans and malaria parasites has been ongoing for millennia. Fully understanding the evolved human response to malaria is impossible without comparative study of parasites in our non-human primate relatives. Though laboratory primates are fruitful models, the complexity of wild primates infected in a natural transmission system may be a more suitable comparison for contextualizing malaria infections in human patients. Here, we investigate the genetic mechanisms underlying the immune response to Hepatocystis, a close relative of human-infective malaria, in a population of wild Ugandan red colobus monkeys. We find that the genes involved have considerable overlap with those active in human malaria patients. Like Plasmodium, Hepatocystis induces changes in blood cell type and may cause the host to produce blood components outside of the bone marrow or alter metabolism related to the production of lipids. Our work helps to identify the genetic mechanisms underlying the arms race between primates and malaria parasites, providing fundamental evolutionary insight. Such comparative work on the interaction between wild non-human primates and malaria parasites can identify ways in which primates have evolved resistance to malaria parasites, and further investigation of such implicated genes may lead to novel potential therapeutic and vaccine targets.

evolutionary biology↗

Evolutionary and phylogenetic insights from a nuclear genome sequence of the extinct, giant subfossil koala lemur Megaladapis edwardsi

No endemic Madagascar animal with body mass >10 kg survived a relatively recent wave of extinction on the island. From morphological and isotopic analyses of skeletal subfossil remains we can reconstruct some of the biology and behavioral ecology of giant lemurs (primates; up to ~160 kg), elephant birds (up to ~860 kg), and other extraordinary Malagasy megafauna that survived well into the past millennium. Yet much about the evolutionary biology of these now extinct species remains unknown, along with persistent phylogenetic uncertainty in some cases. Thankfully, despite the challenges of DNA preservation in tropical and sub-tropical environments, technical advances have enabled the recovery of ancient DNA from some Malagasy subfossil specimens. Here we present a nuclear genome sequence (~2X coverage) for one of the largest extinct lemurs, the koala lemur Megaladapis edwardsi (~85kg). To support the testing of key phylogenetic and evolutionary hypotheses we also generated new high-coverage complete nuclear genomes for two extant lemur species, Eulemur rufifrons and Lepilemur mustelinus, and we aligned these sequences with previously published genomes for three other extant lemur species and 47 non-lemur vertebrates. Our phylogenetic results confirm that Megaladapis is most closely related to the extant Lemuridae (typified in our analysis by E. rufifrons) to the exclusion of L. mustelinus, which contradicts morphology-based phylogenies. Our evolutionary analyses identified significant convergent evolution between M. edwardsi and extant folivorous primates (colobine monkeys) and ungulate herbivores (horses) in genes encoding protein products that function in the biodegradation of plant toxins and nutrient absorption. These results suggest that koala lemurs were highly adapted to a leaf-based diet, which may also explain their convergent craniodental morphology with the small-bodied folivore Lepilemur.

genomics↗

Genomic signatures of extreme body size divergence in baboons

Kinda and gray-footed chacma baboons occupy opposite extremes of the body size distribution in extant baboons (genus Papio). In order to detect signatures of natural selection in these two species, we genotyped 24,790 genome-wide autosomal SNPs from populations of Zambian baboons using double digest RADseq. We scanned the genome for evidence of selection by identifying regions with extreme differentiation between populations. We find evidence of selection on body size influencing multiple genes in one or both species, including FGF1, ATXN2, and PRKCE. We also find an enriched signal of selection associated with biological processes involved in multicellular organism growth and development, cell proliferation and cell growth, nutrient metabolism, and chondrocyte differentiation. Finally, we find that selection has impacted components of the CCKR signaling pathway, which regulates food intake and metabolism, and the JAK/STAT signaling pathway, which mediates the effect of cytokine signals on processes including epiphyseal chondrocyte proliferation essential for longitudinal bone growth. Our findings highlight promising avenues for future studies disentangling the genetic architecture of body size in primates including humans.

evolutionary biology↗

Genome-wide ancestry and introgression in a Zambian baboon hybrid zone

Hybridization in nature offers unique insights into the process of natural selection in incipient species and their hybrids. In order to evaluate the patterns and targets of selection, we examine a recently discovered ba-boon hybrid zone in the Kafue River valley of Zambia, where Kinda baboons (Papio kindae) and gray-footed chacma baboons (P. ursinus griseipes) coexist with hybridization. We genotyped baboons at 14,962 variable genome-wide autosomal markers using double-digest RADseq. We compare ancestry patterns from this genome-wide dataset to previously reported ancestry from mitochondrial-DNA and Y-chromosome sources. We also fit a Bayesian genomic cline model to scan for genes with extreme patterns of introgression. We show that the Kinda baboon Y chromosome has penetrated the species boundary to a greater extent than either mitochondrial DNA or the autosomal chromosomes. We also find evidence for overall restricted introgression in the JAK/STAT signaling pathway. Echoing results in other species including humans, we find evidence for enhanced and/or directional introgression of immune-related genes or pathways including the toll-like receptor pathway, the blood coagulation pathway, and the LY96 gene. Finally we show enhanced introgression and excess chacma baboon ancestry in the sperm tail gene ODF2. Together, our results eluci-date the dynamics of introgressive hybridization in a primate system while highlighting genes and pathways under selection.

evolutionary biology↗

Natural selection contributed to immunological differences between human hunter-gatherers and agriculturalists

The shift from a hunter-gatherer (HG) to an agricultural (AG) mode of subsistence is believed to have been associated with profound changes in the burden and diversity of pathogens across human populations. Yet, the extent to which the advent of agriculture may have impacted the evolution of the human immune system remains unknown. Here we present a comparative study of variation in the transcriptional responses of peripheral blood mononuclear cells to bacterial and viral stimuli between Batwa rainforest hunter-gatherers and Bakiga agriculturalists from Uganda. We observed increased divergence between hunter-gatherers and agriculturalists in the transcriptional response to viruses compared to that for bacterial stimuli. We demonstrate that a significant fraction of these transcriptional differences are under genetic control, and we show that positive natural selection has helped to shape population differences in immune regulation. Across the set of genetic variants underlying inter-population immune response differences, however, the signatures of positive selection were disproportionately observed in the rainforest hunter-gatherers. This result is counter to expectations based on the popularized notion that shifts in pathogen exposure due to the advent of agriculture imposed radically heightened selective pressures in agriculturalist populations.

evolutionary biology↗

Assessing connectivity despite high diversity in island populations of the malaria mosquito Anopheles gambiae

Documenting isolation is notoriously difficult for species with vast polymorphic populations. High proportions of shared variation impede estimation of connectivity, even despite leveraging information from many genetic markers. We overcome these impediments by combining classical analysis of neutral variation with assays of the structure of selected variation, demonstrated using populations of the principal African malaria vector Anopheles gambiae. Accurate estimation of mosquito migration is crucial for efforts to combat malaria. Modeling and cage experiments suggest that mosquito gene drive systems will enable malaria eradication, but establishing safety and efficacy requires identification of isolated populations in which to conduct field-testing. We assess Lake Victoria islands as candidate sites, finding one island 30 kilometers offshore is as differentiated from mainland samples as populations from across the continent. Collectively, our results suggest sufficient contemporary isolation of these islands to warrant consideration as field-testing locations and illustrate shared adaptive variation as a useful proxy for connectivity in highly polymorphic species.

evolutionary biology↗

Polygenic adaptation and convergent evolution across both growth and cardiac genetic pathways in African and Asian rainforest hunter-gatherers

Different human populations facing similar environmental challenges have sometimes evolved convergent biological adaptations, for example hypoxia resistance at high altitudes and depigmented skin in northern latitudes on separate continents. The pygmy phenotype (small adult body size), a characteristic of hunter-gatherer populations inhabiting both African and Asian tropical rainforests, is often highlighted as another case of convergent adaptation in humans. However, the degree to which phenotypic convergence in this polygenic trait is due to convergent vs. population-specific genetic changes is unknown. To address this question, we analyzed high-coverage sequence data from the protein-coding portion of the genomes (exomes) of two pairs of populations, Batwa rainforest hunter-gatherers and neighboring Bakiga agriculturalists from Uganda, and Andamanese rainforest hunter-gatherers (Jarawa and Onge) and Brahmin agriculturalists from India. We observed signatures of convergent positive selection between the Batwa and Andamanese rainforest hunter-gatherers across the set of genes with annotated growth factor binding functions (p < 0.001). Unexpectedly, for the rainforest groups we also observed convergent and population-specific signatures of positive selection in pathways related to cardiac development (e.g. cardiac muscle tissue development; p = 0.001). We hypothesize that the growth hormone sub-responsiveness likely underlying the pygmy phenotype may have led to compensatory changes in cardiac pathways, in which this hormone also plays an essential role. Importantly, in the agriculturalist populations we did not observe similar patterns of positive selection on sets of genes associated with either growth or cardiac development, indicating that our results most likely reflect a history of convergent adaptation to the similar ecology of rainforest hunter-gatherers rather than a more common or general evolutionary pattern for human populations.

genomics↗