Single-cell strand sequencing of a macaque genome reveals multiple nested inversions and breakpoint reuse during primate evolution
- Flavia Angela Maria Maggiolini1,
- Ashley D. Sanders2,
- Colin James Shew3,
- Arvis Sulovari4,
- Yafei Mao4,
- Marta Puig5,
- Claudia Rita Catacchio1,
- Maria Dellino1,
- Donato Palmisano1,
- Ludovica Mercuri1,
- Miriana Bitonto1,
- David Porubský4,
- Mario Cáceres5,6,
- Evan E. Eichler4,7,
- Mario Ventura1,
- Megan Y. Dennis3,
- Jan O. Korbel2 and
- Francesca Antonacci1
- 1Dipartimento di Biologia, Università degli Studi di Bari “Aldo Moro,” Bari 70125, Italy;
- 2European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany;
- 3Genome Center, MIND Institute, and Department of Biochemistry & Molecular Medicine, University of California, Davis, California 95616, USA;
- 4Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington 98195, USA;
- 5Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona 08193, Spain;
- 6ICREA, Barcelona 08010, Spain;
- 7Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA
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.
Footnotes
-
[Supplemental material is available for this article.]
-
Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.265322.120.
- Received April 30, 2020.
- Accepted September 2, 2020.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.