Title: Novel Insights into the Landscape of Crossover and Noncrossover Events in Rhesus Macaques ( Macaca mulatta )
Abstract Meiotic recombination landscapes differ greatly between distantly and closely related taxa, populations, individuals, sexes, and even within genomes; however, the factors driving this variation are yet to be well elucidated. Here, we directly estimate contemporary crossover rates and, for the first time, noncrossover rates in rhesus macaques (Macaca mulatta) from four three-generation pedigrees comprising 32 individuals. We further compare these results with historical, demography-aware, linkage disequilibrium–based recombination rate estimates. From paternal meioses in the pedigrees, 165 crossover events with a median resolution of 22.3 kb were observed, corresponding to a male autosomal map length of 2,357 cM—approximately 15% longer than an existing linkage map based on human microsatellite loci. In addition, 85 noncrossover events with a mean tract length of 155 bp were identified—similar to the tract lengths observed in the only other two primates in which noncrossovers have been studied to date, humans and baboons. Consistent with observations in other placental mammals with PRDM9-directed recombination, crossover (and to a lesser extent noncrossover) events in rhesus macaques clustered in intergenic regions and toward the chromosomal ends in males—a pattern in broad agreement with the historical, sex-averaged recombination rate estimates—and evidence of GC-biased gene conversion was observed at noncrossover sites.  more » « less
Award ID(s):
2045343 2126303
PAR ID:
10487523
Author(s) / Creator(s):
; ; ; ; ;
Editor(s):
Kosiol, Carolin
Publisher / Repository:
Oxford University Press on behalf of Society for Molecular Biology and Evolution
Date Published:
Journal Name:
Genome Biology and Evolution
Volume:
16
Issue:
1
ISSN:
1759-6653
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ABSTRACT As a major model for biomedical research, the rhesus macaque (Macaca mulatta) is one of the most important and heavily studied nonhuman primates. Despite this importance, the level of population structure and subspecific division in this species remains relatively unclear; for example, the number of proposed subspecies in the literature ranges from one to six within China, with additional populations found across India. Motivated by an interest in comparing recombination rate landscapes between rhesus macaque subspecies, we re‐evaluated the demographic history of this group using a previously published data set from 79 wild‐born individuals sampled across 17 regions in China. In so doing, we found that previously published demographic models utilizing five subspecies did not well reproduce empirical levels or patterns of genomic variation. Thus, we re‐performed demographic inference, finding instead multiple lines of support for a single, interbreeding population (i.e., an absence of population structuring), as well as a population size‐change history linking periods of population growth and contraction to historical patterns of glaciation. Finally, utilizing this well‐fitting population history, we inferred a genome‐wide, fine‐scale recombination rate map for this population, finding mean rates consistent with those estimated in other closely related populations and species. However, we also observed notable difference in the fine‐scale landscape between rhesus macaques of Chinese and Indian origin – two populations widely used as models in biomedical research – highlighting the importance of accounting for population‐specific demographic history and recombination rate variation in future population genomic studies of this species. 
    more » « less
  2. 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
  3. In the past decade, several studies have estimated the human per-generation germline mutation rate using large pedigrees. More recently, estimates for various nonhuman species have been published. However, methodological differences among studies in detecting germline mutations and estimating mutation rates make direct comparisons difficult. Here, we describe the many different steps involved in estimating pedigree-based mutation rates, including sampling, sequencing, mapping, variant calling, filtering, and appropriately accounting for false-positive and false-negative rates. For each step, we review the different methods and parameter choices that have been used in the recent literature. Additionally, we present the results from a ‘Mutationathon,’ a competition organized among five research labs to compare germline mutation rate estimates for a single pedigree of rhesus macaques. We report almost a twofold variation in the final estimated rate among groups using different post-alignment processing, calling, and filtering criteria, and provide details into the sources of variation across studies. Though the difference among estimates is not statistically significant, this discrepancy emphasizes the need for standardized methods in mutation rate estimations and the difficulty in comparing rates from different studies. Finally, this work aims to provide guidelines for computational and statistical benchmarks for future studies interested in identifying germline mutations from pedigrees. 
    more » « less
  4. Gaining a better understanding of rates and patterns of meiotic recombination is crucial for improving evolutionary genomic modelling, 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., non-crossovers) as well as the landscapes in more distantly-related primates (i.e., strepsirrhines) remains limited owing to difficulties associated with both the identification of non-crossover tracts as well as species sampling. Thus, in order to elucidate recombination patterns in this under-studied branch of the primate clade, we here characterize crossover and non-crossover landscapes in aye-ayes utilizing whole-genome sequencing data from six three-generation pedigrees as well as 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
  5. 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