Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
CaltechAUTHORS
Published November 22, 2018 | Supplemental Material + Submitted + Published
Journal Article Open

Improved reference genome of Aedes aegypti informs arbovirus vector control

Matthews, Benjamin J. ORCID icon
Antoshechkin, Igor ORCID icon

Abstract

Female Aedes aegypti mosquitoes infect more than 400 million people each year with dangerous viral pathogens including dengue, yellow fever, Zika and chikungunya. Progress in understanding the biology of mosquitoes and developing the tools to fight them has been slowed by the lack of a high-quality genome assembly. Here we combine diverse technologies to produce the markedly improved, fully re-annotated AaegL5 genome assembly, and demonstrate how it accelerates mosquito science. We anchored physical and cytogenetic maps, doubled the number of known chemosensory ionotropic receptors that guide mosquitoes to human hosts and egg-laying sites, provided further insight into the size and composition of the sex-determining M locus, and revealed copy-number variation among glutathione S-transferase genes that are important for insecticide resistance. Using high-resolution quantitative trait locus and population genomic analyses, we mapped new candidates for dengue vector competence and insecticide resistance. AaegL5 will catalyse new biological insights and intervention strategies to fight this deadly disease vector.

Additional Information

© 2018 Springer Nature Limited. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received 28 December 2017; Accepted 05 October 2018; Published 14 November 2018. Code availability: The overview of the Hi-C workflow, as well as modifications to 3D-DNA associated with AaegL5, is shared on GitHub at https://github.com/theaidenlab/AGWG-merge. The source code and executable version of Juicebox Assembly Tools are available at http://aidenlab.org/assembly. Data files and scripts used for the final polishing of scaffolded, gap-filled assembly are available at https://github.com/skingan/AaegL5_FinalPolish. Data availability: All raw data have been deposited at NCBI under the following BioProject accession numbers: PRJNA318737 (primary Pacific Biosciences data, Hi-C sequencing primary data and processed contact maps, whole-genome sequencing data from a single male (Fig. 4d) and pools of male and females (Fig. 3d), Bionano optical mapping data (Figs. 3c, 4c) and 10X linked-read sequences (Extended Data Fig. 8a and Supplementary Data 21)); PRJNA236239 (RNA-seq reads and de novo transcriptome assembly13 (Extended Data Fig. 2c and Supplementary Data 4, 5, 7, 9)); PRJNA209388 (RNA-seq reads for developmental time points57 (Fig. 1h and Supplementary Data 4–6, 9)); PRJNA419241 (RNA-seq reads from adult reproductive tissues and developmental time points, Verily Life Sciences (Fig. 1h and Supplementary Data 4, 5, 8, 9)); PRJNA393466 (full-length Pacific Biosciences Iso-Seq transcript sequencing); PRJNA418406 (ATAC-seq data from adult female brains at three points in the gonotrophic cycle (Extended Data Fig. 2c, d and data not shown)); PRJNA419379 (whole-genome sequencing data from four colonies (Fig. 4d and Extended Data Fig. 9a, b)); PRJNA399617 (restriction-site-associated DNA-sequencing data (Fig. 5a–d)); PRJNA393171 (exome-sequencing data (Fig. 5e-g)). Intermediate results related to the AaegL5 assembly are also available via GitHub (http://github.com/theaidenlab/AGWG-merge) and have been uploaded to GEO (GSE113256). The Hi-C maps are available via http://aidenlab.org/juicebox. The complete mitochondrial genome is available as Genbank accession MF194022.1, RefSeq accession NC_035159.1. The final genome assembly and annotation are available from the NCBI Assembly Resource under accession GCF_002204515.2. We thank R. Andino; S. Emrich and D. Lawson (Vectorbase); A. A. James, M. Kunitomi, C. Nusbaum, D. Severson, N. Whiteman; T. Dickinson, M. Hartley and B. Rice (Dovetail Genomics) for early participation in the AGWG; C. Bargmann, D. Botstein, E. Jarvis and E. Lander for encouragement and facilitation. N. Keivanfar, D. Jaffe and D. M. Church (10X Genomics) prepared DNA for structural-variant analysis. We thank A. Harmon of the New York Times and acknowledge generous pro bono data and analysis from our corporate collaborators. This research was supported in part by federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under grant number U19AI110818 to the Broad Institute (S.N.R. and D.E.N.); USDA 2017-05741 (E.L.A.); NSF PHY-1427654 Center for Theoretical Biological Physics (E.L.A.); NIH Intramural Research Program, National Library of Medicine and National Human Genome Research Institute (A.M.P. and S.K.) and the following extramural NIH grants: R01AI101112 (J.R.P.), R35GM118336 (R.S.M. and W.J.G.), R21AI121853 (M.V.S., I.V.S. and A.S.), R01AI123338 (Z.T.), T32GM007739 (M.H.), NIH/NCATS UL1TR000043 (Rockefeller University), DP2OD008540 (E.L.A.), U01AI088647, 1R01AI121211 (W.C.B. IV), Fogarty Training Grant D43TW001130-08, U01HL130010 (E.L.A.), UM1HG009375 (E.L.A), 5K22AI113060 (O.S.A.), 1R21AI123937 (O.S.A.), and R00DC012069 (C.S.M.); Defence Advanced Research Project Agency: HR0011-17-2- 0047 (O.S.A.). Other support was provided by Jane Coffin Childs Memorial Fund (B.J.M.), Center for Theoretical Biological Physics postdoctoral fellowship (O.D.), Robertson Foundation (L.Z.), and McNair & Welch (Q-1866) Foundations (E.L.A.), French Government's Investissement d'Avenir program, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases (grant ANR-10-LABX-62-IBEID to L.L.), Agence Nationale de la Recherche grant ANR-17-ERC2-0016-01 (L.L.), European Union's Horizon 2020 research and innovation program under ZikaPLAN grant agreement no. 734584 (L.L.), Pew and Searle Scholars Programs (C.S.M.), Klingenstein-Simons Fellowship in the Neurosciences (C.S.M.). A.M.W., B.J.W., J.E.C. and S.N.M. were supported by Verily Life Sciences. L.B.V. is an investigator of the Howard Hughes Medical Institute. Author Contributions: B.J.M. and L.B.V. conceived the study, coordinated data collection and analysis, designed the figures and wrote the paper with input from all authors. B.J.M. developed and distributed animals and/or DNA of the LVP_AGWG strain. P.P., M.L.S. and J.M. carried out Pacific Biosciences sample preparation and sequencing. S.B.K., R.H., J.K., S.K. and A.M.P. were involved in genome assembly. A.R.H., S.C., J.L. and H.C. carried out Bionano optical mapping. O.D., S.S.B., A.D.O., A.P.A. and E.L.A. carried out Hi-C sample preparation, scaffolding and deduplication. The following authors contributed analysis and data to the indicated figures: B.R.E., A.G.-S. and J.R.P. (Fig. 1c); J.S.J. (Fig. 1d); L.Z. (Fig. 1f); E.C., V.S.J., V.K.K., M.R.M., T.D.M. and B.J.M. (Fig. 1g); I.A., O.S.A., J.E.C., A.M.W., B.J.W., R.G.G.K., S.N.M. and B.J.M. (Fig. 1h); C.S.M., H.M.R., Z.Z., N.H.R. and B.J.M. (Fig. 2); Z.T., M.V.S., I.V.S., A.S., Y.W., J.T., A.C.D., A.R.H. and B.J.M. (Fig. 3); G.D.W., B.J.M., A.R.H., S.B.K., A.M.P. and S.K. (Fig. 4); A.F., I.F., T.F., G.R. and L.L. (Fig. 5a–d); C.L.C., K.S.-R., W.C.B. and B.J.M. (Fig. 5e–g); B.J.M. (Extended Data Fig. 1a); J.S.J. (Extended Data Fig. 1b); O.D., S.S.B., A.D.O., A.P.A. and E.L.A. (Extended Data Fig. 1c, d); S.B.K., J.K., O.D., E.L.A., S.K., A.M.P. and B.J.M. (Extended Data Fig. 1e); A.R.H. and B.J.M. (Extended Data Fig. 2a); E.C., V.S.J., V.K.K., M.R.M., T.D.M. and B.J.M. (Extended Data Fig. 2b); M.H. and B.J.M. (Extended Data Fig. 2c, d); A.S., I.V.S. and M.V.S. (Extended Data Fig. 2e); C.A.B.-S., S.S. and C.A.H. (Extended Data Fig. 2f); C.S.M., H.M.R., Z.Z., N.H.R. and B.J.M. (Extended Data Figs. 3–7); ; S.N.R. and D.E.N. (Extended Data Fig. 8a); W.J.G., R.S.M., O.D., E.L.A. and B.J.M. (Extended Data Fig. 8b, c); W.J.G. and R.S.M. (Extended Data Fig. 8d); J.E.C., A.M.W., B.J.W., R.G.G.K. and S.N.M. (Extended Data Fig. 9a, b); B.R.E., A.G.-S. and J.R.P. (Extended Data Fig 9c, d); A.F., I.F., T.F, G.R. and L.L. (Extended Data Fig. 10a, b); G.J.L., A.K.J., V.R., S.D.B., F.A.P. and D.B.S. (Extended Data Fig. 10c, d); A.R.H. (Supplementary Data 1); L.Z. (Supplementary Data 2, 3); I.A., O.S.A., J.E.C., A.M.W., B.J.W., R.G.G.K., S.N.M. and B.J.M. (Supplementary Data 4–9); E.C., V.S.J., V.K.K., M.R.M. and T.D.M. (Supplementary Data 10, 11); A.S., I.V.S. and M.V.S. (Supplementary Data 12); S.R. and A.S.R. (Supplementary Data 13); C.A.B.-S., S.S. and C.A.H. (Supplementary Data 14–16); C.S.M., H.M.R., Z.Z., N.H.R. and B.J.M. (Supplementary Data 17–20); S.N.R. and D.E.N. (Supplementary Data 21); W.J.G. and R.S.M. (Supplementary Data 22); G.D.W. and B.J.M. (Supplementary Data 23); G.J.L., A.K.J., V.R., S.D.B., F.A.P. and D.B.S. (Supplementary Data 24). Competing interests: P.P., M.L.S., J.M., S.B.K., R.H. and J.K. are employees of Pacific Biosciences, a company developing single-molecule sequencing technologies. J.L., S.C., H.C. and A.R.H. are employees of Bionano Genomics and own company stock options. O.D., S.S.B., A.D.O., A.P.A. and E.L.A. are inventors on a US provisional patent application 62/347,605, filed 8 June 2016, by the Baylor College of Medicine and the Broad Institute.

Attached Files

Published - s41586-018-0692-z.pdf

Submitted - 240747.full.pdf

Supplemental Material - 41586_2018_692_Fig10_ESM.jpg

Supplemental Material - 41586_2018_692_Fig11_ESM.jpg

Supplemental Material - 41586_2018_692_Fig12_ESM.jpg

Supplemental Material - 41586_2018_692_Fig13_ESM.jpg

Supplemental Material - 41586_2018_692_Fig14_ESM.jpg

Supplemental Material - 41586_2018_692_Fig15_ESM.jpg

Supplemental Material - 41586_2018_692_Fig6_ESM.jpg

Supplemental Material - 41586_2018_692_Fig7_ESM.jpg

Supplemental Material - 41586_2018_692_Fig8_ESM.jpg

Supplemental Material - 41586_2018_692_Fig9_ESM.jpg

Supplemental Material - 41586_2018_692_MOESM1_ESM.pdf

Supplemental Material - 41586_2018_692_MOESM2_ESM.pdf

Supplemental Material - 41586_2018_692_MOESM3_ESM.zip

Files

240747.full.pdf
Files (35.6 MB)
Name Size Download all
md5:f3b311ec98147c8b6172387f4df472c1
5.1 MB Preview Download
md5:d72a8ad9ccfee4a02d47a9e4ef41c96f
244.9 kB Preview Download
md5:a9fbec2ccb9b449497ed851fe7e7bbb3
145.4 kB Preview Download
md5:d1c6d88da6e249da3bffb694ea8a13b9
163.2 kB Preview Download
md5:248a8d20fb1edb7c17426f732838968c
208.2 kB Preview Download
md5:e98eceab9136e0fb1fb9cfa58d30f19a
139.3 kB Preview Download
md5:d49ed44f5733557505feabbbe7432ee6
93.6 kB Preview Download
md5:ea78ba3f491c5a4cece64fca93299ddd
6.9 MB Preview Download
md5:312943bdaf271f81ca306d418602ef77
220.8 kB Preview Download
md5:8253e8e0b6b99ac68255615e6bef1617
80.3 kB Preview Download
md5:323e1554d3bb6d8c2ec58973ddbe4261
114.0 kB Preview Download
md5:4c3cc1d78e7922a8cbb24e6e1a021a18
118.3 kB Preview Download
md5:a658df4ba70aa80bfa2fe4b16f16e6e2
123.6 kB Preview Download
md5:6836fe9026747c9b6002060a010d4584
21.7 MB Preview Download
md5:e3d87aee617d269816532ac01adef8d7
373.3 kB Preview Download

Additional details

Additional titles Identifiers Related works Funding Dates
Created:
August 19, 2023
Modified:
October 23, 2023