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The aye-aye (Daubentonia madagascariensis) is one of the 25 most endangered primate species in the world, maintaining amongst the lowest genetic diversity of any primate measured to date. Characterizing patterns of genetic variation within aye-aye populations, and the relative influences of neutral and selective processes in shaping that variation, is thus important for future conservation efforts. In this study, we performed the first whole-genome scans for recent positive and balancing selection in the species, utilizing high-coverage population genomic data from newly sequenced individuals. We generated null thresholds for our genomic scans by creating an evolutionarily appropriate baseline model that incorporates the demographic history of this aye-aye population, and identified a small number of candidate genes. Most notably, a suite of genes involved in olfaction — a key trait in these nocturnal primates — were identified as experiencing long-term balancing selection. We also conducted analyses to quantify the expected statistical power to detect positive and balancing selection in this population using site frequency spectrum-based inference methods, once accounting for the potentially confounding contributions of population history, recombination and mutation rate variation, and purifying and background selection. This work, presenting the first high-quality, genome-wide polymorphism data across the functional regions of the aye-aye genome, thus provides important insights into the landscape of episodic selective forces in this highly endangered species.
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Investigating the effects of chimerism on the inference of selection: quantifying genomic targets of purifying, positive, and balancing selection in common marmosets (Callithrix jacchus)
Abstract The common marmoset (Callithrix jacchus) is of considerable biomedical importance, yet there remains a need to characterize the evolutionary forces shaping empirically observed patterns of genomic variation in the species. However, two uncommon biological traits potentially prevent the use of standard population genetic approaches in this primate: a high frequency of twin births and the prevalence of hematopoietic chimerism. Here we characterize the impact of these biological features on the inference of natural selection, and directly model twinning and chimerism when performing inference of the distribution of fitness effects to characterize general selective dynamics as well as when scanning the genome for loci shaped by the action of episodic positive and balancing selection. Results suggest a generally increased degree of purifying selection relative to human populations, consistent with the larger estimated effective population size of common marmosets. Furthermore, genomic scans based on an appropriate evolutionary baseline model reveal a small number of genes related to immunity, sensory perception, and reproduction to be strong sweep candidates. Notably, two genes in the major histocompatibility complex were found to have strong evidence of being maintained by balancing selection, in agreement with observations in other primate species. Taken together, this work, presenting the first whole-genome characterization of selective dynamics in the common marmoset, thus provides important insights into the landscape of both persistent and episodic selective forces in this species.
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- Award ID(s):
- 2045343
- PAR ID:
- 10660982
- Publisher / Repository:
- Heredity
- Date Published:
- Journal Name:
- Heredity
- Volume:
- 134
- Issue:
- 10-11
- ISSN:
- 0018-067X
- Page Range / eLocation ID:
- 645 to 657
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Macdonald, S (Ed.)Abstract The aye-aye (Daubentonia madagascariensis) is one of the 25 most endangered primate species in the world, maintaining amongst the lowest genetic diversity of any primate measured to date. Characterizing patterns of genetic variation within aye-aye populations, and the relative influences of neutral and selective processes in shaping that variation, is thus important for future conservation efforts. In this study, we performed the first whole-genome scans for positive and balancing selection in the species, utilizing high-coverage population genomic data from newly sequenced individuals. We generated null thresholds for our genomic scans by creating an evolutionarily appropriate baseline model that incorporates the demographic history of this aye-aye population, and identified a small number of candidate genes. Most notably, a suite of genes involved in olfaction—a key trait in these nocturnal primates—were identified as experiencing long-term balancing selection. We also conducted analyses to quantify the expected statistical power to detect positive and balancing selection in this population using site frequency spectrum–based inference methods, once accounting for the potentially confounding contributions of population history, mutation and recombination rate variation, as well as purifying and background selection. This work, presenting the first high-quality, genome-wide polymorphism data across the functional regions of the aye-aye genome, thus provides important insights into the landscape of episodic selective forces in this highly endangered species.more » « less
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ABSTRACT The common marmoset (Callithrix jacchus) is an important model in biomedical and clinical research, particularly for the study of age-related, neurodegenerative, and neurodevelopmental disorders (due to their biological similarities with humans), infectious disease (due to their susceptibility to a variety of pathogens), as well as developmental biology (due to their short gestation period relative to many other primates). Yet, while being one of the most commonly used non-human primate models for research, the population genomics of the common marmoset remains relatively poorly characterized, despite the critical importance of this knowledge in many areas of research including genome-wide association studies, models of polygenic risk scores, and scans for the targets of selection. This neglect owes, at least in part, to two biological peculiarities related to the reproductive mode of the species — frequent twinning and sibling chimerism — which are likely to affect standard population genetic approaches relying on assumptions underlying the Wright-Fisher model. Using high-quality population genomic data, we here infer the rates and landscapes of mutation and recombination — two fundamental processes dictating the levels and patterns of genetic variability — in the presence of these biological features, and discuss our findings in light of recent work in primates. Our results suggest that, while the species exhibits relatively low neutral mutation rates, rates of recombination are in the range of those observed in other anthropoids. Moreover, the recombination landscape of common marmosets, like that of many vertebrates, is dominated by PRDM9-mediated hotspots, with artificial intelligence-based models predicting an intricate 3D-structure of the species-specific PRDM9-DNA binding complexin silico. Apart from providing novel insights into the population genetics of common marmosets, given the importance of the availability of fine-scale maps of mutation and recombination for evolutionary inference, this work will also serve as a valuable resource to aid future genomic research in this widely studied system.more » « less
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Harris, Kelley (Ed.)Abstract As a species of considerable biomedical importance, characterizing the evolutionary genomics of the common marmoset (Callithrix jacchus) is of significance across multiple fields of research. However, at least 2 peculiarities of this species potentially preclude commonly utilized population genetic modeling and inference approaches: a high frequency of twin births and hematopoietic chimerism. We here investigate these effects within the context of demographic inference, demonstrating via simulation that neglecting these biological features results in significant mis-inference of the underlying population history. Based upon this result, we develop a novel approximate Bayesian inference approach accounting for both common twin births and chimeric sampling. In addition, we newly present population genomic data from 15 individuals sequenced to high coverage and utilize gene-level annotations to identify neutrally evolving intergenic regions appropriate for demographic inference. Applying our developed methodology, we estimate a well-fitting population history for this species, which suggests robust ancestral and current population sizes, as well as a size reduction roughly 7,000 years ago likely associated with a shift from arboreal to savanna vegetation in north-eastern Brazil during this period.more » « less
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Guschanski, Katerina (Ed.)Abstract Gaining a better understanding of the rates and patterns of meiotic recombination is crucial for improving evolutionary genomic modeling, with applications ranging from demographic to selective inference. Although previous research has provided important insights into the landscape of crossovers in humans and other haplorrhines, our understanding of both the considerably more common outcome of recombination (i.e. noncrossovers) as well as the landscapes in more distantly related primates (i.e. strepsirrhines) remains limited owing to difficulties associated with both the identification of noncrossover tracts as well as species sampling. Thus, in order to elucidate recombination patterns in this understudied branch of the primate clade, we here characterize crossover and noncrossover landscapes in aye-ayes utilizing whole-genome sequencing data from six three-generation pedigrees and three two-generation multi-sibling families, and in so doing provide novel insights into this important evolutionary process shaping genomic diversity in one of the world's most critically endangered primate species.more » « less
- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1038/s41437-025-00804-7
