PT  - JOURNAL ARTICLE
AU  - Gregg W.C Thomas
AU  - Richard J. Wang
AU  - Jelena Nguyen
AU  - R. Alan Harris
AU  - Muthuswamy Raveendran
AU  - Jeffrey Rogers
AU  - Matthew W. Hahn
TI  - Origins and long-term patterns of copy-number variation in rhesus macaques
AID  - 10.1101/749416
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 749416
4099  - http://biorxiv.org/content/early/2019/08/28/749416.short
4100  - http://biorxiv.org/content/early/2019/08/28/749416.full
AB  - Mutations play a key role in the development of disease in an individual and the evolution of traits within species. Recent work in humans and other primates has clarified the origins and patterns of single nucleotide variants, showing that most arise in the father’s germline during spermatogenesis. It remains unknown whether larger mutations, such as deletions and duplications of hundreds or thousands of nucleotides, follow similar patterns. Such mutations lead to copy-number variation (CNV) within and between species, and can have profound effects by deleting or duplicating genes. Here we analyze patterns of CNV mutations in 32 rhesus macaque individuals from 14 parent-offspring trios. We find the rate of CNV mutations per generation is low (less than one per genome) and we observe no correlation between parental age and the number of CNVs that are passed on to offspring. We also examine segregating CNVs within the rhesus macaque sample and compare them to a similar dataset from humans, finding that both species have far more segregating deletions than duplications. We contrast this with long-term patterns of gene copy-number evolution between 17 mammals, where the proportion of deletions that become fixed along the macaque lineage is much smaller than the proportion of segregating deletions. These results suggest purifying selection acting on deletions, such that the majority of them are removed from the population over time. Rhesus macaques are an important biomedical model organism, so these results will aid in our understanding of this species and the disease models it supports.