No retraction, correction or concern found when last checked on Oct 31, 2026.
Six reference-quality genomes reveal evolution of bat adaptations
David Jebb, Zixia Huang, Martin Pippel and 26 more
Nature · 2020
Abstract
Bats possess extraordinary adaptations, including flight, echolocation, extreme longevity and unique immunity. High-quality genomes are crucial for understanding the molecular basis and evolution of these traits. Here we incorporated long-read sequencing and state-of-the-art scaffolding protocols 1 to generate, to our knowledge, the first reference-quality genomes of six bat species ( Rhinolophus ferrumequinum , Rousettus aegyptiacus , Phyllostomus discolor , Myotis myotis , Pipistrellus kuhlii and Molossus molossus ). We integrated gene projections from our ‘Tool to infer Orthologs from Genome Alignments’ (TOGA) software with de novo and homology gene predictions as well as short- and long-read transcriptomics to generate highly complete gene annotations. To resolve the phylogenetic position of bats within Laurasiatheria, we applied several phylogenetic methods to comprehensive sets of orthologous protein-coding and noncoding regions of the genome, and identified a basal origin for bats within Scrotifera. Our genome-wide screens revealed positive selection on hearing-related genes in the ancestral branch of bats, which is indicative of laryngeal echolocation being an ancestral trait in this clade. We found selection and loss of immunity-related genes (including pro-inflammatory NF-κB regulators) and expansions of anti-viral APOBEC3 genes, which highlights molecular mechanisms that may contribute to the exceptional immunity of bats. Genomic integrations of diverse viruses provide a genomic record of historical tolerance to viral infection in bats. Finally, we found and experimentally validated bat-specific variation in microRNAs, which may regulate bat-specific gene-expression programs. Our reference-quality bat genomes provide the resources required to uncover and validate the genomic basis of adaptations of bats, and stimulate new avenues of research that are directly relevant to human health and disease 1 .
Shown for reading. Its publisher allows quoting it, not republishing it.
References 97
- 1.
Teeling EC, et al. Bat biology, genomes, and the Bat1K project: to generate chromosome-level genomes for all living bat species. Annu. Rev. Anim. Biosci. 2018;6:23-46.
Not in our library10.1146/annurev-animal-022516-022811
- 2.
Simmons, N. B. & Cirranello, A. L. Bat Species of the World: A Taxonomic and Geographic Database, https://batnames.org/ (2020).
Not in our library
- 3.
- 4.
Huang Z, et al. Longitudinal comparative transcriptomics reveals unique mechanisms underlying extended healthspan in bats. Nat. Ecol. Evol. 2019;3:1110-1120.
Not in our library10.1038/s41559-019-0913-3
- 5.
Vernes SC, Wilkinson GS. Behaviour, biology and evolution of vocal learning in bats. Phil. Trans. R. Soc. Lond. B. 2020;375:20190061.
Not in our library10.1098/rstb.2019.0061
- 6.
Jones G, Teeling EC, Rossiter SJ. From the ultrasonic to the infrared: molecular evolution and the sensory biology of bats. Front. Physiol. 2013;4:117.
Not in our library10.3389/fphys.2013.00117
- 7.
Teeling EC, et al. A molecular phylogeny for bats illuminates biogeography and the fossil record. Science. 2005;307:580-584.
Not in our library10.1126/science.1105113
- 8.
- 9.
Nowoshilow S, et al. The axolotl genome and the evolution of key tissue formation regulators. Nature. 2018;554:50-55.
Not in our library10.1038/nature25458
- 10.
Tischler, G. in Computational Intelligence Methods for Bioinformatics and Biostatistics (CIBB 2017) (eds Bartoletti, M. et al.) 103–114 (Springer, 2019).
Not in our library
- 11.
Tischler, G. & Myers, E. W. Non hybrid long read consensus using local de Bruijn graph assembly. Preprint at https://www.biorxiv.org/content/10.1101/106252v1 (2017).
Not in our library
- 12.
Dong D, et al. The genomes of two bat species with long constant frequency echolocation calls. Mol. Biol. Evol. 2017;34:20-34.
Not in our library10.1093/molbev/msw231
- 13.
Eckalbar WL, et al. Transcriptomic and epigenomic characterization of the developing bat wing. Nat. Genet. 2016;48:528-536.
Not in our library10.1038/ng.3537
- 14.
Parker J, et al. Genome-wide signatures of convergent evolution in echolocating mammals. Nature. 2013;502:228-231.
Not in our library10.1038/nature12511
- 15.
Pavlovich SS, et al. The Egyptian Rousette genome reveals unexpected features of bat antiviral immunity. Cell. 2018;173:1098-1110.
Not in our library10.1016/j.cell.2018.03.070
- 16.
Seim I, et al. Genome analysis reveals insights into physiology and longevity of the Brandt’s bat Myotis brandtii. Nat. Commun. 2013;4:2212.
Not in our library10.1038/ncomms3212
- 17.
Wen M, et al. Exploring the genome and transcriptome of the cave nectar bat Eonycteris spelaea with PacBio long-read sequencing. Gigascience. 2018;7:giy116.
Not in our library10.1093/gigascience/giy116
- 18.
- 19.
Zhang G, et al. Comparative analysis of bat genomes provides insight into the evolution of flight and immunity. Science. 2013;339:456-460.
Not in our library10.1126/science.1230835
- 20.
Bejerano G, et al. Ultraconserved elements in the human genome. Science. 2004;304:1321-1325.
Not in our library10.1126/science.1098119
- 21.
Nature Biotechnology Editorial. A reference standard for genome biology. Nat. Biotechnol. 2018;36:1121.
Not in our library10.1038/nbt.4318
- 22.
- 23.
Pace JK, Feschotte C. The evolutionary history of human DNA transposons: evidence for intense activity in the primate lineage. Genome Res. 2007;17:422-432.
Not in our library10.1101/gr.5826307
- 24.
Foley NM, Springer MS, Teeling EC. Mammal madness: is the mammal tree of life not yet resolved? Phil. Trans. R. Soc. Lond. B. 2016;371:20150140.
Not in our library10.1098/rstb.2015.0140
- 25.
Doronina L, et al. Speciation network in Laurasiatheria: retrophylogenomic signals. Genome Res. 2017;27:997-1003.
Not in our library10.1101/gr.210948.116
- 26.
Springer, M. S. & Gatesy, J. An ABBA-BABA test for introgression using retroposon insertion data. Preprint at https://www.biorxiv.org/content/10.1101/709477v1 (2019).
Not in our library
- 27.
Kalyaanamoorthy S, Minh BQ, Wong TKF, von Haeseler A, Jermiin LS. ModelFinder: fast model selection for accurate phylogenetic estimates. Nat. Methods. 2017;14:587-589.
Not in our library10.1038/nmeth.4285
- 28.
Nguyen LT, Schmidt HA, von Haeseler A, Minh BQ. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol. Biol. Evol. 2015;32:268-274.
Not in our library10.1093/molbev/msu300
- 29.
- 30.
Springer MS, Gatesy J. On the importance of homology in the age of phylogenomics. Syst. Biodivers. 2018;16:210-228.
Not in our library10.1080/14772000.2017.1401016
- 31.
Nishihara H, Hasegawa M, Okada N. Pegasoferae, an unexpected mammalian clade revealed by tracking ancient retroposon insertions. Proc. Natl Acad. Sci. USA. 2006;103:9929-9934.
Not in our library10.1073/pnas.0603797103
- 32.
Tsagkogeorga G, Parker J, Stupka E, Cotton JA, Rossiter SJ. Phylogenomic analyses elucidate the evolutionary relationships of bats. Curr. Biol. 2013;23:2262-2267.
Not in our library10.1016/j.cub.2013.09.014
- 33.
Jermiin LS, Poladian L, Charleston MA. Is the “Big Bang” in animal evolution real? Science. 2005;310:1910-1911.
Not in our library10.1126/science.1122440
- 34.
- 35.
Ho SY, Jermiin L. Tracing the decay of the historical signal in biological sequence data. Syst. Biol. 2004;53:623-637.
Not in our library10.1080/10635150490503035
- 36.
Jermiin LS, Catullo RA, Holland BR. A new phylogenetic protocol: dealing with model misspecification and confirmation bias in molecular phylogenetics. NAR Genom. Bioinf. 2020;2:lqaa041.
Not in our library10.1093/nargab/lqaa041
- 37.
Chou J, et al. A comparative study of SVDquartets and other coalescent-based species tree estimation methods. BMC Genomics. 2015;16:S2.
Not in our library10.1186/1471-2164-16-s10-s2
- 38.
Smith MD, et al. Less is more: an adaptive branch-site random effects model for efficient detection of episodic diversifying selection. Mol. Biol. Evol. 2015;32:1342-1353.
Not in our library10.1093/molbev/msv022
- 39.
Pond SL, Frost SD, Muse SV. HyPhy: hypothesis testing using phylogenies. Bioinformatics. 2005;21:676-679.
Not in our library10.1093/bioinformatics/bti079
- 40.
Yang Z. PAML 4: phylogenetic analysis by maximum likelihood. Mol. Biol. Evol. 2007;24:1586-1591.
Not in our library10.1093/molbev/msm088
- 41.
Kantarci S, et al. Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai–Barrow and facio-oculo-acoustico-renal syndromes. Nat. Genet. 2007;39:957-959.
Not in our library10.1038/ng2063
- 42.
Tan J, Prakash MD, Kaiserman D, Bird PI. Absence of SERPINB6A causes sensorineural hearing loss with multiple histopathologies in the mouse inner ear. Am. J. Pathol. 2013;183:49-59.
Not in our library10.1016/j.ajpath.2013.03.009
- 43.
Walsh T, et al. Genomic duplication and overexpression of TJP2/ZO-2 leads to altered expression of apoptosis genes in progressive nonsyndromic hearing loss DFNA51. Am. J. Hum. Genet. 2010;87:101-109.
Not in our library10.1016/j.ajhg.2010.05.011
- 44.
Wang Z, et al. Prenatal development supports a single origin of laryngeal echolocation in bats. Nat. Ecol. Evol. 2017;1:0021.
Not in our library10.1038/s41559-016-0021
- 45.
Gunn MD, et al. A B-cell-homing chemokine made in lymphoid follicles activates Burkitt’s lymphoma receptor-1. Nature. 1998;391:799-803.
Not in our library10.1038/35876
- 46.
Vendelin J, et al. Downstream target genes of the neuropeptide S-NPSR1 pathway. Hum. Mol. Genet. 2006;15:2923-2935.
Not in our library10.1093/hmg/ddl234
- 47.
Luong P, et al. INAVA–ARNO complexes bridge mucosal barrier function with inflammatory signaling. eLife. 2018;7:e38539.
Not in our library10.7554/elife.38539
- 48.
Saddawi-Konefka R, et al. Nrf2 induces IL-17D to mediate tumor and virus surveillance. Cell Rep. 2016;16:2348-2358.
Not in our library10.1016/j.celrep.2016.07.075
- 49.
Barker BR, Taxman DJ, Ting JP. Cross-regulation between the IL-1β/IL-18 processing inflammasome and other inflammatory cytokines. Curr. Opin. Immunol. 2011;23:591-597.
Not in our library10.1016/j.coi.2011.07.005
- 50.
Flo TH, et al. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature. 2004;432:917-921.
Not in our library10.1038/nature03104
- 51.
Hase K, et al. Uptake through glycoprotein 2 of FimH+ bacteria by M cells initiates mucosal immune response. Nature. 2009;462:226-230.
Not in our library10.1038/nature08529
- 52.
Yang J, et al. The I-TASSER suite: protein structure and function prediction. Nat. Methods. 2015;12:7-8.
Not in our library10.1038/nmeth.3213
- 53.
- 54.
Wang W, Yang Y, Li L, Shi Y. Synleurin, a novel leucine-rich repeat protein that increases the intensity of pleiotropic cytokine responses. Biochem. Biophys. Res. Commun. 2003;305:981-988.
Not in our library10.1016/s0006-291x(03)00876-3
- 55.
Bridgewood C, et al. IL-36γ has proinflammatory effects on human endothelial cells. Exp. Dermatol. 2017;26:402-408.
Not in our library10.1111/exd.13228
- 56.
Johnston A, et al. IL-1F5, -F6, -F8, and -F9: a novel IL-1 family signaling system that is active in psoriasis and promotes keratinocyte antimicrobial peptide expression. J. Immunol. 2011;186:2613-2622.
Not in our library10.4049/jimmunol.1003162
- 57.
Nishida A, et al. Increased expression of interleukin-36, a member of the interleukin-1 cytokine family, in inflammatory bowel disease. Inflamm. Bowel Dis. 2016;22:303-314.
Not in our library10.1097/mib.0000000000000654
- 58.
Hayward JA, et al. Differential evolution of antiretroviral restriction factors in pteropid bats as revealed by APOBEC3 gene complexity. Mol. Biol. Evol. 2018;35:1626-1637.
Not in our library10.1093/molbev/msy048
- 59.
- 60.
Roper N, et al. APOBEC mutagenesis and copy-number alterations are drivers of proteogenomic tumor evolution and heterogeneity in metastatic thoracic tumors. Cell Rep. 2019;26:2651-2666.
Not in our library10.1016/j.celrep.2019.02.028
- 61.
Salter JD, Bennett RP, Smith HC. The APOBEC protein family: united by structure, divergent in function. Trends Biochem. Sci. 2016;41:578-594.
Not in our library10.1016/j.tibs.2016.05.001
- 62.
- 63.
- 64.
Hayward A, Grabherr M, Jern P. Broad-scale phylogenomics provides insights into retrovirus–host evolution. Proc. Natl Acad. Sci. USA. 2013;110:20146-20151.
Not in our library10.1073/pnas.1315419110
- 65.
Skirmuntt EC, Katzourakis A. The evolution of endogenous retroviral envelope genes in bats and their potential contribution to host biology. Virus Res. 2019;270:197645.
Not in our library10.1016/j.virusres.2019.197645
- 66.
Xu X, Zhao H, Gong Z, Han GZ. Endogenous retroviruses of non-avian/mammalian vertebrates illuminate diversity and deep history of retroviruses. PLoS Pathog. 2018;14:e1007072.
Not in our library10.1371/journal.ppat.1007072
- 67.
Katzourakis A, Tristem M, Pybus OG, Gifford RJ. Discovery and analysis of the first endogenous lentivirus. Proc. Natl Acad. Sci. USA. 2007;104:6261-6265.
Not in our library10.1073/pnas.0700471104
- 68.
Heimberg AM, Sempere LF, Moy VN, Donoghue PC, Peterson KJ. MicroRNAs and the advent of vertebrate morphological complexity. Proc. Natl Acad. Sci. USA. 2008;105:2946-2950.
Not in our library10.1073/pnas.0712259105
- 69.
Moran Y, Agron M, Praher D, Technau U. The evolutionary origin of plant and animal microRNAs. Nat. Ecol. Evol. 2017;1:0027.
Not in our library10.1038/s41559-016-0027
- 70.
- 71.
Kent WJ. BLAT—the BLAST-like alignment tool. Genome Res. 2002;12:656-664.
Not in our library10.1101/gr.229202
- 72.
Gremme G, Brendel V, Sparks ME, Kurtz S. Engineering a software tool for gene structure prediction in higher organisms. Inf. Softw. Technol. 2005;47:965-978.
Not in our library10.1016/j.infsof.2005.09.005
- 73.
- 74.
Sharma V, Hiller M. Increased alignment sensitivity improves the usage of genome alignments for comparative gene annotation. Nucleic Acids Res. 2017;45:8369-8377.
Not in our library10.1093/nar/gkx554
- 75.
Kent WJ, Baertsch R, Hinrichs A, Miller W, Haussler D. Evolution’s cauldron: duplication, deletion, and rearrangement in the mouse and human genomes. Proc. Natl Acad. Sci. USA. 2003;100:11484-11489.
Not in our library10.1073/pnas.1932072100
- 76.
Sharma V, Schwede P, Hiller M. CESAR 2.0 substantially improves speed and accuracy of comparative gene annotation. Bioinformatics. 2017;33:3985-3987.
Not in our library10.1093/bioinformatics/btx527
- 77.
Stanke M, Diekhans M, Baertsch R, Haussler D. Using native and syntenically mapped cDNA alignments to improve de novo gene finding. Bioinformatics. 2008;24:637-644.
Not in our library10.1093/bioinformatics/btn013
- 78.
Hoff KJ, Lange S, Lomsadze A, Borodovsky M, Stanke M. BRAKER1: unsupervised RNA-seq-based genome annotation with GeneMark-ET and AUGUSTUS. Bioinformatics. 2016;32:767-769.
Not in our library10.1093/bioinformatics/btv661
- 79.
Kim D, Paggi JM, Park C, Bennett C, Salzberg SL. Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat. Biotechnol. 2019;37:907-915.
Not in our library10.1038/s41587-019-0201-4
- 80.
- 81.
- 82.
Platt RN, Blanco-Berdugo L, Ray DA. Accurate transposable element annotation is vital when analyzing new genome assemblies. Genome Biol. Evol. 2016;8:403-410.
Not in our library10.1093/gbe/evw009
- 83.
Smit, A. F. A., Hubley, R. & Green, P. RepeatMasker Open-4.0, http://www.repeatmasker.org (2013–2015)
Not in our library
- 84.
Abrusán G, Grundmann N, DeMester L, Makalowski W. TEclass—a tool for automated classification of unknown eukaryotic transposable elements. Bioinformatics. 2009;25:1329-1330.
Not in our library10.1093/bioinformatics/btp084
- 85.
- 86.
Li W, Godzik A. Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics. 2006;22:1658-1659.
Not in our library10.1093/bioinformatics/btl158
- 87.
Wicker T, et al. A unified classification system for eukaryotic transposable elements. Nat. Rev. Genet. 2007;8:973-982.
Not in our library10.1038/nrg2165
- 88.
Hecker N, Hiller M. A genome alignment of 120 mammals highlights ultraconserved element variability and placenta-associated enhancers. Gigascience. 2020;9:giz159.
Not in our library10.1093/gigascience/giz159
- 89.
De Bie T, Cristianini N, Demuth JP, Hahn MW. CAFE: a computational tool for the study of gene family evolution. Bioinformatics. 2006;22:1269-1271.
Not in our library10.1093/bioinformatics/btl097
- 90.
Tabari E, Su Z. PorthoMCL: parallel orthology prediction using MCL for the realm of massive genome availability. Big Data Anal. 2017;2:4.
Not in our library10.1186/s41044-016-0019-8
- 91.
Mi H, et al. The PANTHER database of protein families, subfamilies, functions and pathways. Nucleic Acids Res. 2005;33:D284-D288.
Not in our library10.1093/nar/gki078
- 92.
Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J. Mol. Biol. 1990;215:403-410.
Not in our library10.1016/s0022-2836(05)80360-2
- 93.
Larsson A. AliView: a fast and lightweight alignment viewer and editor for large datasets. Bioinformatics. 2014;30:3276-3278.
Not in our library10.1093/bioinformatics/btu531
- 94.
Stamatakis A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics. 2014;30:1312-1313.
Not in our library10.1093/bioinformatics/btu033
- 95.
Nawrocki EP, Kolbe DL, Eddy SR. Infernal 1.0: inference of RNA alignments. Bioinformatics. 2009;25:1335-1337.
Not in our library10.1093/bioinformatics/btp157
- 96.
Devanna P, et al. Next-gen sequencing identifies non-coding variation disrupting miRNA-binding sites in neurological disorders. Mol. Psychiatry. 2018;23:1375-1384.
Not in our library10.1038/mp.2017.30
- 97.
Devanna P, van de Vorst M, Pfundt R, Gilissen C, Vernes SC. Genome-wide investigation of an ID cohort reveals de novo 3′ UTR variants affecting gene expression. Hum. Genet. 2018;137:717-721.
Not in our library10.1007/s00439-018-1925-9
Cited by papers we hold 6
- A beginner’s guide to manual curation of transposable elements · 2022Corrected
- Nipah virus W protein harnesses nuclear 14-3-3 to inhibit NF-κB-induced proinflammatory response · 2021Not checked
- DNA methylation predicts age and provides insight into exceptional longevity of bats · 2021Corrected
- Towards complete and error-free genome assemblies of all vertebrate species · 2021No notice
- Common ground: The foundation of interdisciplinary research on bat disease emergence. · 2020Not checked
- Novel Insights Into Immune Systems of Bats · 2020No notice
Reads
Read by people on this page
None yet.
Checked or read by AI through naulon
None yet.
A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.
Are you an author?
Is this your paper?
Claim it to add your note and be paid when agents cite it. Free.