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ABSTRACT The rate of input of new genetic mutations, and the rate at which that variation is reshuffled, are key evolutionary processes shaping genomic diversity. Importantly, these rates vary not just across populations and species but also across individual genomes. Despite previous studies having demonstrated that failing to account for rate heterogeneity across the genome can bias the inference of both selective and neutral population genetic processes, mutation and recombination rate maps have to date only been generated for a relatively small number of organisms. Here, we infer such fine‐scale maps for the aye‐aye (Daubentonia madagascariensis)—a highly endangered strepsirrhine that represents one of the earliest splits in the primate clade and thus stands as an important outgroup to the more commonly studied haplorrhines—utilizing a recently released fully annotated genome combined with high‐quality population sequencing data. We compare our indirectly inferred rates to previous pedigree‐based estimates, finding further evidence of relatively low mutation and recombination rates in aye‐ayes compared to other primates.
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Inferring the landscapes of mutation and recombination in the common marmoset (Callithrix jacchus) in the presence of twinning and hematopoietic chimerism
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.
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- Award ID(s):
- 2045343
- PAR ID:
- 10660986
- Publisher / Repository:
- bioRxiv
- Date Published:
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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ABSTRACT Along with germline mutations, meiotic recombination plays a fundamental role in shaping genetic diversity and thus directly influences a species’ potential adaptive response to environmental change, amongst other features. Despite the recombination landscape being of central importance for a variety of questions in molecular evolution, the genome-wide distribution and frequency of recombination remains to be elucidated in many non-human primate species. Utilizing novel high-coverage genomic data from three multi-sibling families, we here provide the first estimates of the rates and patterns of crossover and non-crossover recombination in coppery titi monkeys (Plecturocebus cupreus) — a socially monogamous, pair-bonded primate that serves as an important model in behavioral research. Consistent with haplorrhines, crossover and non-crossover recombination in this platyrrhine are frequently localized at PRDM9-mediated hotspots, characterized by a 15-mer binding motif with substantial similarities to the degenerate 13-mer motif found in humans. The sex-averaged crossover rate in coppery titi monkeys is comparable with those of other primates; however, no significant difference in recombination rates was observed between the sexes, despite a pronounced maternal age effect in the species. Similarities also exist with regards to the sex-specific genomic distribution of non-crossover events, though the minimal conversion tract lengths of extended events was observed to be considerably longer in maternally-inherited non-crossovers. Taken together, these similarities and differences in the recombination landscape relative to other primates highlight the importance of incorporating species-specific rates and patterns in evolutionary models, and the resources provided here will thus serve to aid future studies in this important primate model system.more » « less
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ABSTRACT Despite being a primate of considerable biomedical interest, particularly as a model for social behavior and neurobiology, the evolutionary processes shaping genetic variation in the coppery titi monkey (Plecturocebus cupreus) remain largely uncharacterized. Utilizing divergence and polymorphism data together with a recently published high-quality, annotated genome, we here infer the first fine-scale maps of mutation and recombination rates in this platyrrhine. We find a mean genome-wide mutation rate of between 0.93 × 10-8and 1.61 × 10-8per site per generation and a mean genome-wide recombination rate of 0.975 cM/Mb, in line with fine-scale rates estimated in other primates. In addition to providing novel biological insights into the mutation and recombination rates in this emerging model species for behavioral research, these fine-scale maps also improve our understanding of how the processes of mutation and recombination shape genetic variation in the coppery titi monkey genome, and their incorporation into evolutionary models will be a necessary aspect of future downstream inference of other evolutionary processes required to elucidate the genetic factors underlying the phenotypic traits studied in this species.more » « less
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Inferring fine-scale mutation and recombination rate maps in aye-ayes (Daubentonia madagascariensis)The rate of input of new genetic mutations, and the rate at which that variation is reshuffled, are key evolutionary processes shaping genomic diversity. Importantly, these rates vary not just across populations and species, but also across individual genomes. Despite previous studies having demonstrated that failing to account for rate heterogeneity across the genome can bias the inference of both selective and neutral population genetic processes, mutation and recombination rate maps have to date only been generated for a relatively small number of organisms. Here, we infer such fine-scale maps for the aye-aye (Daubentonia madagascariensis) – a highly endangered strepsirrhine that represents one of the earliest splits in the primate clade, and thus stands as an important outgroup to the more commonly-studied haplorrhines – utilizing a recently released fully-annotated genome combined with high-quality population sequencing data. We compare our indirectly inferred rates to previous pedigree-based estimates, finding further evidence of relatively low mutation and recombination rates in aye-ayes compared to other primates.more » « less
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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.more » « less
- Free Publicly Accessible Full Text
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Accepted Manuscript
- Posted Content:
- https://doi.org/10.1101/2025.07.01.662565
