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Single-cell strand sequencing of a macaque genome reveals multiple nested inversions and breakpoint reuse during primate evolution

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Item Type:Article
Title:Single-cell strand sequencing of a macaque genome reveals multiple nested inversions and breakpoint reuse during primate evolution
Creators Name:Maggiolini, F.A.M. and Sanders, A.D. and Shew, C.J. and Sulovari, A. and Mao, Y. and Puig, M. and Catacchio, C.R. and Dellino, M. and Palmisano, D. and Mercuri, L. and Bitonto, M. and Porubský, D. and Cáceres, M. and Eichler, E.E. and Ventura, M. and Dennis, M.Y. and Korbel, J.O. and Antonacci, F.
Abstract:Rhesus macaque is an Old World monkey that shared a common ancestor with human ∼25 Myr ago and is an important animal model for human disease studies. A deep understanding of its genetics is therefore required for both biomedical and evolutionary studies. Among structural variants, inversions represent a driving force in speciation and play an important role in disease predisposition. Here we generated a genome-wide map of inversions between human and macaque, combining single-cell strand sequencing with cytogenetics. We identified 375 total inversions between 859 bp and 92 Mbp, increasing by eightfold the number of previously reported inversions. Among these, 19 inversions flanked by segmental duplications overlap with recurrent copy number variants associated with neurocognitive disorders. Evolutionary analyses show that in 17 out of 19 cases, the Hominidae orientation of these disease-associated regions is always derived. This suggests that duplicated sequences likely played a fundamental role in generating inversions in humans and great apes, creating architectures that nowadays predispose these regions to disease-associated genetic instability. Finally, we identified 861 genes mapping at 156 inversions breakpoints, with some showing evidence of differential expression in human and macaque cell lines, thus highlighting candidates that might have contributed to the evolution of species-specific features. This study depicts the most accurate fine-scale map of inversions between human and macaque using a two-pronged integrative approach, such as single-cell strand sequencing and cytogenetics, and represents a valuable resource toward understanding of the biology and evolution of primate species.
Keywords:Chromosome Breakpoints, Chromosome Inversion, Disease, Molecular Evolution, Gene Expression Regulation, Genome, Genomics, Heterozygote, Fluorescence In Situ Hybridization, Genetic Recombination, DNA Sequence Analysis, Single-Cell Analysis, Animals, Macaca mulatta
Source:Genome Research
Publisher:Cold Spring Harbor Laboratory Press
Page Range:1680-1693
Date:November 2020
Official Publication:https://doi.org/10.1101/gr.265322.120
PubMed:View item in PubMed

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