TY - JOUR
T1 - Single-cell strand sequencing of a macaque genome reveals multiple nested inversions and breakpoint reuse during primate evolution
AU - Maria Maggiolini, Flavia Angela
AU - Sanders, Ashley D.
AU - Shew, Colin James
AU - Sulovari, Arvis
AU - Mao, Yafei
AU - Puig, Marta
AU - Catacchio, Claudia Rita
AU - Dellino, Maria
AU - Palmisano, Donato
AU - Mercuri, Ludovica
AU - Bitonto, Miriana
AU - Porubský, David
AU - Cáceres, Mario
AU - Eichler, Evan E.
AU - Ventura, Mario
AU - Dennis, Megan Y.
AU - Korbel, Jan O.
AU - Antonacci, Francesca
N1 - Funding Information:
We thank T. Brown for critical review of the manuscript, Alejandra Delprat for help with the PCR validations, and Mira Mastoras and Pietro D’Addabbo for bioinformatics support. This work was supported by “Fondi di Ateneo, University of Bari” grant (grant number CUP H92F17000190005) to F.A., by the Agencia Estatal de Investigación (AEI, Spain) and the European Regional Development Fund (FEDER, EU; grant number BFU2016-77244-R) grant to M.C., by European Research Council Consolidator Grant MOSAIC grant (grant number 773026) to J.O.K., by the National Institutes of Health, National Institute of Neurological Disorders and Stroke (R00NS083627) grant to M.Y.D., and by U.S. National Institutes of Health (NIH) Clinical Center grants (grant numbers HG002385 and HG010169) to E.E.E. E.E.E. is an investigator of the Howard Hughes Medical Institute, and M.Y.D. is a Sloan fellow (FG-2016-6814).
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
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U2 - 10.1101/gr.265322.120
DO - 10.1101/gr.265322.120
M3 - Article
C2 - 33093070
AN - SCOPUS:85095461665
VL - 30
SP - 1680
EP - 1693
JO - Genome Research
JF - Genome Research
SN - 1088-9051
IS - 11
ER -