Fine-Mapping Complex Inversion Breakpoints and Investigating Somatic Pairing in the Anopheles gambiae Species Complex Using Proximity-Ligation Sequencing.

Autor:	Corbett-Detig RB; Department of Biomolecular Engineering, University of California Santa Cruz, California 95064 rucorbet@ucsc.edu nbesansk@nd.edu.; Genomics Institute, University of California Santa Cruz, California 95064., Said I; Department of Biomolecular Engineering, University of California Santa Cruz, California 95064., Calzetta M; Dipartimento di Sanità Pubblica e Malattie Infettive and Istituto Pasteur Italia-Fondazione Cenci-Bolognetti, Università di Roma 'La Sapienza', 00185 Rome, Italy., Genetti M; Department of Biomolecular Engineering, University of California Santa Cruz, California 95064., McBroome J; Department of Biomolecular Engineering, University of California Santa Cruz, California 95064., Maurer NW; Department of Biomolecular Engineering, University of California Santa Cruz, California 95064., Petrarca V; Dipartimento di Sanità Pubblica e Malattie Infettive and Istituto Pasteur Italia-Fondazione Cenci-Bolognetti, Università di Roma 'La Sapienza', 00185 Rome, Italy., Della Torre A; Dipartimento di Sanità Pubblica e Malattie Infettive and Istituto Pasteur Italia-Fondazione Cenci-Bolognetti, Università di Roma 'La Sapienza', 00185 Rome, Italy., Besansky NJ; Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, Indiana 46556 rucorbet@ucsc.edu nbesansk@nd.edu.
Jazyk:	angličtina
Zdroj:	Genetics [Genetics] 2019 Dec; Vol. 213 (4), pp. 1495-1511. Date of Electronic Publication: 2019 Oct 30.
DOI:	10.1534/genetics.119.302385
Abstrakt:	Chromosomal inversions are fundamental drivers of genome evolution. In the main Afrotropical malaria vector species, belonging to the Anopheles gambiae species complex, inversions play an important role in local adaptation and have a rich history of cytological study. Despite the importance and ubiquity of some chromosomal inversions across the species complex, inversion breakpoints are often challenging to map molecularly due to the presence of large repetitive regions. Here, we develop an approach that uses Hi-C sequencing data to molecularly fine-map the breakpoints of inversions. We demonstrate that this approach is robust and likely to be widely applicable for both identification and fine-mapping inversion breakpoints in species whose inversions have heretofore been challenging to characterize. We apply our method to interrogate the previously unknown inversion breakpoints of 2Rbc and 2Rd in An. coluzzii We found that inversion breakpoints occur in large repetitive regions, and, strikingly, among three inversions analyzed, two breakpoints appear to be reused in two separate inversions. These breakpoint-adjacent regions are strongly enriched for the presence of a 30 bp satellite repeat sequence. Because low frequency inversion breakpoints are not correlated with genomic regions containing this satellite, we suggest that interrupting this particular repeat may result in arrangements with higher relative fitness. Additionally, we use heterozygous individuals to quantitatively investigate the impacts of somatic pairing in the regions immediately surrounding inversion breakpoints. Finally, we discuss important considerations for possible applications of this approach for inversion breakpoint identification in a range of organisms. (Copyright © 2019 by the Genetics Society of America.)
Databáze:	MEDLINE
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