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Gene losses in the common vampire bat illuminate molecular adaptations to blood feeding

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Blumer, Moritz, Brown, Tom, Freitas, Mariella Bontempo, Destro, Ana Luiza, Oliveira, Juraci A., Morales, Ariadna E., Schell, Tilman, Greve, Carola +9 more·2022·Science Advances
DOI 10.1126/sciadv.abm6494PMC PMC8956264

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Abstract

Vampire bats are the only mammals that feed exclusively on blood. To uncover genomic changes associated with this dietary adaptation, we generated a haplotype-resolved genome of the common vampire bat and screened 27 bat species for genes that were specifically lost in the vampire bat lineage. We found previously unknown gene losses that relate to reduced insulin secretion ( FFAR1 and SLC30A8 ), limited glycogen stores ( PPP1R3E ), and a unique gastric physiology ( CTSE ). Other gene losses likely reflect the biased nutrient composition ( ERN2 and CTRL ) and distinct pathogen diversity of blood ( RNASE7 ) and predict the complete lack of cone-based vision in these strictly nocturnal bats ( PDE6H and PDE6C ). Notably, REP15 loss likely helped vampire bats adapt to high dietary iron levels by enhancing iron excretion, and the loss of CYP39A1 could have contributed to their exceptional cognitive abilities. These findings enhance our understanding of vampire bat biology and the genomic underpinnings of adaptations to blood feeding.

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  • TOGA enables phylogenomic analyses as well as screens for selection patterns and gene losses that are linked to relevant phenotypes.

    “First, by detecting inactivated genes and providing orthologous sequences for codon alignments, TOGA enables phylogenomic analyses as well as screens for selection patterns and gene losses that are linked to relevant phenotypes (6, 35–38).”

    From Integrating gene annotation with orthology inference at scale (2023) · cites this paper as [37]

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  1. [1]R. J. Baker, O. R. P. Bininda-Emonds, H. Mantilla-Meluk, C. A. Porter, R. A. Van Den Bussche, Molecular time scale of diversification of feeding strategy and morphology in New World leaf-nosed bats (Phyllostomidae): A phylogenetic perspective, in Evolutionary History of Bats: Fossils, Molecules and Morphology, G. F. Gunnell, N. B. Simmons, Eds. (Cambridge University Press, 2012), pp. 385–409.
  2. [2]U. Schmidt, Orientation and sensory functions in Desmodus rotundus, in Natural History of Vampire Bats (CRC Press, 2018), pp. 24.
  3. [4]R. S. Heffner, G. Koay, H. E. Heffner, Hearing in American leaf-nosed bats. IV: The common vampire bat, Desmodus rotundus. Hear. Res. 296, 42– 50 (2013). 23194991 PMC3563265
  4. [5]E. O. Gracheva, J. F. Cordero-Morales, J. A. González-Carcacía, N. T. Ingolia, C. Manno, C. I. Aranguren, J. S. Weissman, D. Julius, Ganglion-specific splicing of TRPV1 underlies infrared sensation in vampire bats. Nature 476, 88– 91 (2011). 21814281 PMC3535012
  5. [6]D. K. Riskin, S. Parsons, W. A. Schutt Jr., G. G. Carter, J. W. Hermanson, Terrestrial locomotion of the New Zealand short-tailed bat Mystacina tuberculata and the common vampire bat Desmodus rotundus. J. Exp. Biol. 209, 1725– 1736 (2006). 16621953
  6. [7]J. S. Davis, C. W. Nicolay, S. H. Williams, A comparative study of incisor procumbency and mandibular morphology in vampire bats. J. Morphol. 271, 853– 862 (2010). 20544874
  7. [8]D. H. Low, K. Sunagar, E. A. B. Undheim, S. A. Ali, A. C. Alagon, T. Ruder, T. N. W. Jackson, S. P. Gonzalez, G. F. King, A. Jones, A. Antunes, B. G. Fry, Dracula’s children: Molecular evolution of vampire bat venom. J. Proteomics 89, 95– 111 (2013). 23748026
  8. [10]D. Morton, W. A. Wimsatt, Distribution of iron in the gastrointestinal tract of the common vampire bat: Evidence for macrophage-linked iron clearance. Anat. Rec. 198, 183– 192 (1980). 7212303
  9. [11]A. V. Graça-Souza, C. Maya-Monteiro, G. O. Paiva-Silva, G. R. C. Braz, M. C. Paes, M. H. F. Sorgine, M. F. Oliveira, P. L. Oliveira, Adaptations against heme toxicity in blood-feeding arthropods. Insect Biochem. Mol. Biol. 36, 322– 335 (2006). 16551546
  10. [13]M. B. Freitas, J. F. Queiroz, C. I. Dias Gomes, C. B. Collares-Buzato, H. C. Barbosa, A. C. Boschero, C. A. Gonçalves, E. C. Pinheiro, Reduced insulin secretion and glucose intolerance are involved in the fasting susceptibility of common vampire bats. Gen. Comp. Endocrinol. 183, 1– 6 (2013). 23262275
  11. [14]M. B. Freitas, A. F. Welker, S. F. Millan, E. C. Pinheiro, Metabolic responses induced by fasting in the common vampire bat Desmodus rotundus. J. Comp. Physiol. B 173, 703– 707 (2003). 13680131
  12. [15]M. B. Freitas, C. B. C. Passos, R. B. Vasconcelos, E. C. Pinheiro, Effects of short-term fasting on energy reserves of vampire bats (Desmodus rotundus). Comp. Biochem. Physiol. B Biochem. Mol. Biol. 140, 59– 62 (2005). 15621510
  13. [17]M. L. Zepeda Mendoza, Z. Xiong, M. Escalera-Zamudio, A. K. Runge, J. Thézé, D. Streicker, H. K. Frank, E. Loza-Rubio, S. Liu, O. A. Ryder, J. A. Samaniego Castruita, A. Katzourakis, G. Pacheco, B. Taboada, U. Löber, O. G. Pybus, Y. Li, E. Rojas-Anaya, K. Bohmann, A. Carmona Baez, C. F. Arias, S. Liu, A. D. Greenwood, M. F. Bertelsen, N. E. White, M. Bunce, G. Zhang, T. Sicheritz-Pontén, M. P. T. Gilbert, Hologenomic adaptations underlying the evolution of sanguivory in the common vampire bat. Nat. Ecol. Evol. 2, 659– 668 (2018). 29459707 PMC5868727
  14. [18]Y. T. Gutiérrez-Guerrero, E. Ibarra-Laclette, C. M. Del Río, J. Barrera-Redondo, E. A. Rebollar, J. Ortega, L. León-Paniagua, A. Urrutia, E. Aguirre-Planter, L. E. Eguiarte, Genomic consequences of dietary diversification and parallel evolution due to nectarivory in leaf-nosed bats. Gigascience 9, giaa059 (2020). 32510151 PMC7276932
  15. [19]K. Wang, S. Tian, J. Galindo-González, L. M. Dávalos, Y. Zhang, H. Zhao, Molecular adaptation and convergent evolution of frugivory in Old World and neotropical fruit bats. Mol. Ecol. 29, 4366– 4381 (2020). 32633855
  16. [20]W. Hong, H. Zhao, Vampire bats exhibit evolutionary reduction of bitter taste receptor genes common to other bats. Proc. Biol. Sci. 281, 20141079 (2014). 24966321 PMC4083806
  17. [21]R. Albalat, C. Canestro, Evolution by gene loss. Nat. Rev. Genet. 17, 379– 391 (2016). 27087500
  18. [23]N. Hecker, V. Sharma, M. Hiller, Convergent gene losses illuminate metabolic and physiological changes in herbivores and carnivores. Proc. Natl. Acad. Sci. U.S.A. 116, 3036– 3041 (2019). 30718421 PMC6386725
  19. [24]M. Huelsmann, N. Hecker, M. S. Springer, J. Gatesy, V. Sharma, M. Hiller, Genes lost during the transition from land to water in cetaceans highlight genomic changes associated with aquatic adaptations. Sci. Adv. 5, eaaw6671 (2019). 31579821 PMC6760925
  20. [25]D. Jebb, Z. Huang, M. Pippel, G. M. Hughes, K. Lavrichenko, P. Devanna, S. Winkler, L. S. Jermiin, E. C. Skirmuntt, A. Katzourakis, L. Burkitt-Gray, D. A. Ray, K. A. M. Sullivan, J. G. Roscito, B. M. Kirilenko, L. M. Dávalos, A. P. Corthals, M. L. Power, G. Jones, R. D. Ransome, D. K. N. Dechmann, A. G. Locatelli, S. J. Puechmaille, O. Fedrigo, E. D. Jarvis, M. Hiller, S. C. Vernes, E. W. Myers, E. C. Teeling, Six reference-quality genomes reveal evolution of bat adaptations. Nature 583, 578– 584 (2020). 32699395 PMC8075899
  21. [26]A. Scheben, O. M. Ramos, M. Kramer, S. Goodwin, S. Oppenheim, D. J. Becker, M. C. Schatz, N. B. Simmons, A. Siepel, W Richard Mc Combie, Long-read sequencing reveals rapid evolution of immunity- and cancer-related genes in bats. bioRxiv 10.1101/2020.09.09.290502 [Preprint]. 2021. PMC10510315 37728212 · DOI
  22. [27]D. J. Strick, L. A. Elferink, Rab15 effector protein: A novel protein for receptor recycling from the endocytic recycling compartment. Mol. Biol. Cell 16, 5699– 5709 (2005). 16195351 PMC1289414
  23. [28]I. M. Stasiak, D. A. Smith, T. Ganz, G. J. Crawshaw, J. D. Hammermueller, D. Bienzle, B. N. Lillie, Iron storage disease (hemochromatosis) and hepcidin response to iron load in two species of pteropodid fruit bats relative to the common vampire bat. J. Comp. Physiol. B 188, 683– 694 (2018). 29594459
  24. [29]J. M. Williams, C. A. Duckworth, M. D. Burkitt, A. J. M. Watson, B. J. Campbell, D. M. Pritchard, Epithelial cell shedding and barrier function: A matter of life and death at the small intestinal villus tip. Vet. Pathol. 52, 445– 455 (2015). 25428410 PMC4441880
  25. [30]M. Uhlen, P. Oksvold, L. Fagerberg, E. Lundberg, K. Jonasson, M. Forsberg, M. Zwahlen, C. Kampf, K. Wester, S. Hober, H. Wernerus, L. Björling, F. Ponten, Towards a knowledge-based Human Protein Atlas. Nat. Biotechnol. 28, 1248– 1250 (2010). 21139605
  26. [31]L. A. Elferink, D. J. Strick, Functional properties of rab15 effector protein in endocytic recycling. Methods Enzymol. 403, 732– 743 (2005). 16473635
  27. [32]E. Chen, F. Yang, H. He, Q. Li, W. Zhang, J. Xing, Z. Zhu, J. Jiang, H. Wang, X. Zhao, R. Liu, L. Lei, J. Dong, Y. Pei, Y. Yang, J. Pan, P. Zhang, S. Liu, L. du, Y. Zeng, J. Yang, Alteration of tumor suppressor BMP5 in sporadic colorectal cancer: A genomic and transcriptomic profiling based study. Mol. Cancer 17, 176 (2018). 30572883 PMC6302470
  28. [33]M. J. Brookes, S. Hughes, F. E. Turner, G. Reynolds, N. Sharma, T. Ismail, G. Berx, A. McKie, N. Hotchin, G. J. Anderson, T. Iqbal, C. Tselepis, Modulation of iron transport proteins in human colorectal carcinogenesis. Gut 55, 1449– 1460 (2006). 16641131 PMC1856421
  29. [34]B. A. Neely, M. G. Janech, M. B. Fenton, N. B. Simmons, A. M. Bland, D. J. Becker, Surveying the vampire bat (Desmodus rotundus) serum proteome: A resource for identifying immunological proteins and detecting pathogens. J. Proteome Res. 20, 2547– 2559 (2021). 33840197 PMC9812275
  30. [35]A. D. Mancini, V. Poitout, The fatty acid receptor FFA1/GPR40 a decade later: How much do we know? Trends Endocrinol. Metab. 24, 398– 407 (2013). 23631851
  31. [36]M. G. Latour, T. Alquier, E. Oseid, C. Tremblay, T. L. Jetton, J. Luo, D. C. H. Lin, V. Poitout, GPR40 is necessary but not sufficient for fatty acid stimulation of insulin secretion in vivo. Diabetes 56, 1087– 1094 (2007). 17395749 PMC1853382
  32. [37]M. G. Pedersen, A. Tagliavini, J. C. Henquin, Calcium signaling and secretory granule pool dynamics underlie biphasic insulin secretion and its amplification by glucose: Experiments and modeling. Am. J. Physiol. Endocrinol. Metab. 316, E475– E486 (2019). 30620637
  33. [38]H. Lan, L. M. Hoos, L. Liu, G. Tetzloff, W. Hu, S. J. Abbondanzo, G. Vassileva, E. L. Gustafson, J. A. Hedrick, H. R. Davis, Lack of FFAR1/GPR40 does not protect mice from high-fat diet-induced metabolic disease. Diabetes 57, 2999– 3006 (2008). 18678612 PMC2570396
  34. [39]T. Tomita, H. Masuzaki, H. Iwakura, J. Fujikura, M. Noguchi, T. Tanaka, K. Ebihara, J. Kawamura, I. Komoto, Y. Kawaguchi, K. Fujimoto, R. Doi, Y. Shimada, K. Hosoda, M. Imamura, K. Nakao, Expression of the gene for a membrane-bound fatty acid receptor in the pancreas and islet cell tumours in humans: Evidence for GPR40 expression in pancreatic beta cells and implications for insulin secretion. Diabetologia 49, 962– 968 (2006). 16525841
  35. [40]S. Del Guerra, M. Bugliani, V. D’Aleo, S. Del Prato, U. Boggi, F. Mosca, F. Filipponi, R. Lupi, G-protein-coupled receptor 40 (GPR40) expression and its regulation in human pancreatic islets: The role of type 2 diabetes and fatty acids. Nutr. Metab. Cardiovasc. Dis. 20, 22– 25 (2010). 19758793
  36. [41]S. Edfalk, P. Steneberg, H. Edlund, Gpr40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion. Diabetes 57, 2280– 2287 (2008). 18519800 PMC2518478
  37. [42]T. Yamashima, Dual effects of the non-esterified fatty acid receptor ‘GPR40’ for human health. Prog. Lipid Res. 58, 40– 50 (2015). 25615413
  38. [43]T. J. Nicolson, E. A. Bellomo, N. Wijesekara, M. K. Loder, J. M. Baldwin, A. V. Gyulkhandanyan, V. Koshkin, A. I. Tarasov, R. Carzaniga, K. Kronenberger, T. K. Taneja, G. da Silva Xavier, S. Libert, P. Froguel, R. Scharfmann, V. Stetsyuk, P. Ravassard, H. Parker, F. M. Gribble, F. Reimann, R. Sladek, S. J. Hughes, P. R. V. Johnson, M. Masseboeuf, R. Burcelin, S. A. Baldwin, M. Liu, R. Lara-Lemus, P. Arvan, F. C. Schuit, M. B. Wheeler, F. Chimienti, G. A. Rutter, Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetes-associated variants. Diabetes 58, 2070– 2083 (2009). 19542200 PMC2731533
  39. [44]L. D. Pound, S. A. Sarkar, A. Ustione, P. K. Dadi, M. K. Shadoan, C. E. Lee, J. A. Walters, M. Shiota, O. P. McGuinness, D. A. Jacobson, D. W. Piston, J. C. Hutton, D. R. Powell, R. M. O’Brien, The physiological effects of deleting the mouse SLC30A8 gene encoding zinc transporter-8 are influenced by gender and genetic background. PLOS ONE 7, e40972 (2012). 22829903 PMC3400647
  40. [45]F. Chimienti, S. Devergnas, A. Favier, M. Seve, Identification and cloning of a beta-cell-specific zinc transporter, ZnT-8, localized into insulin secretory granules. Diabetes 53, 2330– 2337 (2004). 15331542
  41. [46]M. F. Dunn, Zinc-ligand interactions modulate assembly and stability of the insulin hexamer – a review. Biometals 18, 295– 303 (2005). 16158220
  42. [48]J. M. Peres, S. Bouhallab, C. Petit, F. Bureau, J. L. Maubois, P. Arhan, D. Bouglé, Improvement of zinc intestinal absorption and reduction of zinc/iron interaction using metal bound to the caseinophosphopeptide 1-25 of β-casein. Reprod. Nutr. Dev. 38, 465– 472 (1998). 9795989
  43. [49]P. Kondaiah, P. A. Sharp, R. Pullakhandam, Zinc induces iron egress from intestinal Caco-2 cells via induction of Hephaestin: A role for PI3K in intestinal iron absorption. Biochem. Biophys. Res. Commun. 523, 987– 992 (2020). 31973819
  44. [50]L. D. Pound, S. A. Sarkar, R. K. P. Benninger, Y. Wang, A. Suwanichkul, M. K. Shadoan, R. L. Printz, J. K. Oeser, C. E. Lee, D. W. Piston, O. P. McGuinness, J. C. Hutton, D. R. Powell, R. M. O’Brien, Deletion of the mouse Slc30a8 gene encoding zinc transporter-8 results in impaired insulin secretion. Biochem. J. 421, 371– 376 (2009). 19450229 PMC2929527
  45. [51]K. J. Bosma, K. E. Syring, J. K. Oeser, J. D. Lee, R. K. P. Benninger, M. E. Pamenter, R. M. O’Brien, Evidence that evolution of the diabetes susceptibility gene SLC30A8 that encodes the zinc transporter ZnT8 drives variations in pancreatic islet zinc content in multiple species. J. Mol. Evol. 87, 147– 151 (2019). 31273433 PMC6699160
  46. [52]P. D. Zalewski, S. H. Millard, I. J. Forbes, O. Kapaniris, A. Slavotinek, W. H. Betts, A. D. Ward, S. F. Lincoln, I. Mahadevan, Video image analysis of labile zinc in viable pancreatic islet cells using a specific fluorescent probe for zinc. J. Histochem. Cytochem. 42, 877– 884 (1994). 8014471
  47. [53]J. R. Hunt, Bioavailability of iron, zinc, and other trace minerals from vegetarian diets. Am. J. Clin. Nutr. 78, 633S– 639S (2003). 12936958
  48. [54]C. E. Semrad, Zinc and intestinal function. Curr. Gastroenterol. Rep. 1, 398– 403 (1999). 10980978
  49. [55]S. Munro, H. Ceulemans, M. Bollen, J. Diplexcito, P. T. W. Cohen, A novel glycogen-targeting subunit of protein phosphatase 1 that is regulated by insulin and shows differential tissue distribution in humans and rodents. FEBS J. 272, 1478– 1489 (2005). 15752363
  50. [56]P. J. Roach, Glycogen and its metabolism. Curr. Mol. Med. 2, 101– 120 (2002). 11949930
  51. [57]M. C. Petersen, D. F. Vatner, G. I. Shulman, Regulation of hepatic glucose metabolism in health and disease. Nat. Rev. Endocrinol. 13, 572– 587 (2017). 28731034 PMC5777172
  52. [58]W. G. Aschenbach, Y. Suzuki, K. Breeden, C. Prats, M. F. Hirshman, S. D. Dufresne, K. Sakamoto, P. G. Vilardo, M. Steele, J. H. Kim, S. L. Jing, L. J. Goodyear, A. A. DePaoli-Roach, The muscle-specific protein phosphatase PP1G/RGL(GM)is essential for activation of glycogen synthase by exercise. J. Biol. Chem. 276, 39959– 39967 (2001). 11522787
  53. [59]M. B. Mehta, S. V. Shewale, R. N. Sequeira, J. S. Millar, N. J. Hand, D. J. Rader, Hepatic protein phosphatase 1 regulatory subunit 3B (Ppp1r3b) promotes hepatic glycogen synthesis and thereby regulates fasting energy homeostasis. J. Biol. Chem. 292, 10444– 10454 (2017). 28473467 PMC5481556
  54. [60]S. M. Crosson, A. Khan, J. Printen, J. E. Pessin, A. R. Saltiel, PTG gene deletion causes impaired glycogen synthesis and developmental insulin resistance. J. Clin. Invest. 111, 1423– 1432 (2003). 12727934 PMC154451
  55. [61]Y. Zhang, J. Gu, L. Wang, Z. Zhao, Y. Pan, Y. Chen, Ablation of PPP1R3G reduces glycogen deposition and mitigates high-fat diet induced obesity. Mol. Cell. Endocrinol. 439, 133– 140 (2017). 27815211
  56. [62]N. Zaidi, C. Hermann, T. Herrmann, H. Kalbacher, Emerging functional roles of cathepsin E. Biochem. Biophys. Res. Commun. 377, 327– 330 (2008). 18938134
  57. [63]T. Saku, H. Sakai, Y. Shibata, Y. Kato, K. Yamamoto, An immunocytochemical study on distinct intracellular localization of cathepsin E and cathepsin D in human gastric cells and various rat cells. J. Biochem. 110, 956– 964 (1991). 1794985
  58. [64]G. R. Ordoñez, L. W. Hillier, W. C. Warren, F. Grützner, C. López-Otín, X. S. Puente, Loss of genes implicated in gastric function during platypus evolution. Genome Biol. 9, R81 (2008). 18482448 PMC2441467
  59. [65]V. Sharma, M. Hiller, Losses of human disease-associated genes in placental mammals. NAR Genom Bioinform 2, lqz012 (2020). 33575564 PMC7671337
  60. [66]A. Bertolotti, X. Z. Wang, I. Novoa, R. Jungreis, K. Schlessinger, J. H. Cho, A. B. West, D. Ron, Increased sensitivity to dextran sodium sulfate colitis in IRE1beta-deficient mice. J. Clin. Invest. 107, 585– 593 (2001). 11238559 PMC199427
  61. [67]J. Iqbal, K. Dai, T. Seimon, R. Jungreis, M. Oyadomari, G. Kuriakose, D. Ron, I. Tabas, M. M. Hussain, IRE1beta inhibits chylomicron production by selectively degrading MTP mRNA. Cell Metab. 7, 445– 455 (2008). 18460335 PMC2435513
  62. [68]J. Iqbal, J. Queiroz, Y. Li, X. C. Jiang, D. Ron, M. M. Hussain, Increased intestinal lipid absorption caused by Ire1β deficiency contributes to hyperlipidemia and atherosclerosis in apolipoprotein E-deficient mice. Circ. Res. 110, 1575– 1584 (2012). 22556338 PMC3384494
  63. [69]D. C. Whitcomb, M. E. Lowe, Human pancreatic digestive enzymes. Dig. Dis. Sci. 52, 1– 17 (2007). 17205399
  64. [70]D. Sun, H. Jin, J. Zhang, X. Tan, Integrated whole genome microarray analysis and immunohistochemical assay identifies COL11A1, GJB2 and CTRL as predictive biomarkers for pancreatic cancer. Cancer Cell Int. 18, 174 (2018). 30410422 PMC6219000
  65. [71]D. Mosztbacher, Z. Jancso, M. Sahin-Toth, Loss of chymotrypsin-like protease (CTRL) alters intrapancreatic protease activation but not pancreatitis severity in mice. Sci. Rep. 10, 11731 (2020). 32678161 PMC7366634
  66. [72]T. L. Hostelley, J. E. Nesmith, E. Larkin, A. Jones, D. Boyes, C. C. Leitch, M. Fontaine, N. A. Zaghloul, Exocrine pancreas proteases regulate β-cell proliferation in zebrafish ciliopathy models and in murine systems. Biol Open 10, (2021). PMC8249909 34125181
  67. [74]I. Razik, B. K. G. Brown, R. A. Page, G. G. Carter, Non-kin adoption in the common vampire bat. R. Soc. Open Sci. 8, 201927 (2021). 33972872 PMC8074576
  68. [75]J. Li-Hawkins, E. G. Lund, A. D. Bronson, D. W. Russell, Expression cloning of an oxysterol 7alpha-hydroxylase selective for 24-hydroxycholesterol. J. Biol. Chem. 275, 16543– 16549 (2000). 10748047
  69. [76]I. P. Grabovec, S. V. Smolskaya, A. V. Baranovsky, V. N. Zhabinskii, Y. V. Dichenko, P. S. Shabunya, S. A. Usanov, N. V. Strushkevich, Ligand-binding properties and catalytic activity of the purified human 24-hydroxycholesterol 7α-hydroxylase, CYP39A1. J. Steroid Biochem. Mol. Biol. 193, 105416 (2019). 31247323
  70. [77]M. Norlin, A. Toll, I. Bjorkhem, K. Wikvall, 24-hydroxycholesterol is a substrate for hepatic cholesterol 7alpha-hydroxylase (CYP7A). J. Lipid Res. 41, 1629– 1639 (2000). 11013305
  71. [78]A. V. Yantsevich, Y. V. Dichenko, F. MacKenzie, D. V. Mukha, A. V. Baranovsky, A. A. Gilep, S. A. Usanov, N. V. Strushkevich, Human steroid and oxysterol 7α-hydroxylase CYP7B1: Substrate specificity, azole binding and misfolding of clinically relevant mutants. FEBS J. 281, 1700– 1713 (2014). 24491228
  72. [79]C. Knabe, T. Sudhop, K. von Bergmann, D. Lütjohann, Degradation of 24S-hydroxycholesterol in men is not regulated by CYP7A1. Int. J. Clin. Pharmacol. Ther. 45, 577– 582 (2007). 18077921
  73. [81]D. Lütjohann, O. Breuer, G. Ahlborg, I. Nennesmo, A. Sidén, U. Diczfalusy, I. Björkhem, Cholesterol homeostasis in human brain: Evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation. Proc. Natl. Acad. Sci. 93, 9799– 9804 (1996). 8790411 PMC38509
  74. [82]A. R. Stiles, J. Kozlitina, B. M. Thompson, J. G. McDonald, K. S. King, D. W. Russell, Genetic, anatomic, and clinical determinants of human serum sterol and vitamin D levels. Proc. Natl. Acad. Sci. U.S.A. 111, E4006– E4014 (2014). 25201972 PMC4183318
  75. [83]S. M. Paul, J. J. Doherty, A. J. Robichaud, G. M. Belfort, B. Y. Chow, R. S. Hammond, D. C. Crawford, A. J. Linsenbardt, H. J. Shu, Y. Izumi, S. J. Mennerick, C. F. Zorumski, The major brain cholesterol metabolite 24(S)-hydroxycholesterol is a potent allosteric modulator of N-methyl-D-aspartate receptors. J. Neurosci. 33, 17290– 17300 (2013). 24174662 PMC3812502
  76. [84]X. Wei, T. Nishi, S. Kondou, H. Kimura, I. Mody, Preferential enhancement of GluN2B-containing native NMDA receptors by the endogenous modulator 24S-hydroxycholesterol in hippocampal neurons. Neuropharmacology 148, 11– 20 (2019). 30594698 PMC6424632
  77. [85]S. Maioli, A. Båvner, Z. Ali, M. Heverin, M. A. M. Ismail, E. Puerta, M. Olin, A. Saeed, M. Shafaati, P. Parini, A. Cedazo-Minguez, I. Björkhem, Is it possible to improve memory function by upregulation of the cholesterol 24S-hydroxylase (CYP46A1) in the brain? PLOS ONE 8, e68534 (2013). 23874659 PMC3712995
  78. [86]T. J. Kotti, D. M. O. Ramirez, B. E. Pfeiffer, K. M. Huber, D. W. Russell, Brain cholesterol turnover required for geranylgeraniol production and learning in mice. Proc. Natl. Acad. Sci. U.S.A. 103, 3869– 3874 (2006). 16505352 PMC1450160
  79. [87]M. Radosevic, J. Planagumà, F. Mannara, A. Mellado, E. Aguilar, L. Sabater, J. Landa, A. García-Serra, E. Maudes, X. Gasull, M. Lewis, J. Dalmau, Allosteric modulation of NMDARs reverses patients’ autoantibody effects in mice. Neurol. Neuroimmunol. Neuroinflamm. 9, e1122 (2022). 34903638 PMC8669659
  80. [88]I. Zoicas, J. Kornhuber, The role of the N-methyl-D-aspartate receptors in social behavior in rodents. Int. J. Mol. Sci. 20, (2019). PMC6887971 31717513
  81. [89]S. P. Ripperger, G. G. Carter, N. Duda, A. Koelpin, B. Cassens, R. Kapitza, D. Josic, J. Berrío-Martínez, R. A. Page, F. Mayer, Vampire bats that cooperate in the lab maintain their social networks in the wild. Curr. Biol. 29, 4139– 4144.e4 (2019). 31679938
  82. [90]G. Baron, H. Stephan, H. D. Frahm, Comparative Neurobiology in Chiroptera: Brain Characteristics in Functional Systems, Ecoethological Adaptation, Adaptive Radiation, and Evolution (Springer, 1996).
  83. [91]H. Monyer, N. Burnashev, D. J. Laurie, B. Sakmann, P. H. Seeburg, Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12, 529– 540 (1994). 7512349
  84. [92]M. Cardoso-Moreira, J. Halbert, D. Valloton, B. Velten, C. Chen, Y. Shao, A. Liechti, K. Ascenção, C. Rummel, S. Ovchinnikova, P. V. Mazin, I. Xenarios, K. Harshman, M. Mort, D. N. Cooper, C. Sandi, M. J. Soares, P. G. Ferreira, S. Afonso, M. Carneiro, J. M. A. Turner, J. L. VandeBerg, A. Fallahshahroudi, P. Jensen, R. Behr, S. Lisgo, S. Lindsay, P. Khaitovich, W. Huber, J. Baker, S. Anders, Y. E. Zhang, H. Kaessmann, Gene expression across mammalian organ development. Nature 571, 505– 509 (2019). 31243369 PMC6658352
  85. [94]S. Kohl, F. Coppieters, F. Meire, S. Schaich, S. Roosing, C. Brennenstuhl, S. Bolz, M. van Genderen, F. C. Riemslag; European Retinal Disease Consortium, R. Lukowski, A. den Hollander, F. P. Cremers, E. de Baere, C. B. Hoyng, B. Wissinger, A nonsense mutation in PDE6H causes autosomal-recessive incomplete achromatopsia. Am. J. Hum. Genet. 91, 527– 532 (2012). 22901948 PMC3511981
  86. [95]C. Brennenstuhl, N. Tanimoto, M. Burkard, R. Wagner, S. Bolz, D. Trifunovic, C. Kabagema-Bilan, F. Paquet-Durand, S. C. Beck, G. Huber, M. W. Seeliger, P. Ruth, B. Wissinger, R. Lukowski, Targeted ablation of the Pde6h gene in mice reveals cross-species differences in cone and rod phototransduction protein isoform inventory. J. Biol. Chem. 290, 10242– 10255 (2015). 25739440 PMC4400339
  87. [96]B. Chang, T. Grau, S. Dangel, R. Hurd, B. Jurklies, E. C. Sener, S. Andreasson, H. Dollfus, B. Baumann, S. Bolz, N. Artemyev, S. Kohl, J. Heckenlively, B. Wissinger, A homologous genetic basis of the murine cpfl1 mutant and human achromatopsia linked to mutations in the PDE6C gene. Proc. Natl. Acad. Sci. U.S.A. 106, 19581– 19586 (2009). 19887631 PMC2780790
  88. [97]T. Grau, N. O. Artemyev, T. Rosenberg, H. Dollfus, O. H. Haugen, E. Cumhur Sener, B. Jurklies, S. Andreasson, C. Kernstock, M. Larsen, E. Zrenner, B. Wissinger, S. Kohl, Decreased catalytic activity and altered activation properties of PDE6C mutants associated with autosomal recessive achromatopsia. Hum. Mol. Genet. 20, 719– 730 (2011). 21127010 PMC3269206
  89. [98]C. A. Emerling, A. D. Widjaja, N. N. Nguyen, M. S. Springer, Their loss is our gain: Regressive evolution in vertebrates provides genomic models for uncovering human disease loci. J. Med. Genet. 54, 787– 794 (2017). 28814606
  90. [99]U. Gröger, L. Wiegrebe, Classification of human breathing sounds by the common vampire bat, Desmodus rotundus. BMC Biol 4, 18 (2006). 16780579 PMC1513255
  91. [100]M. Escalera-Zamudio, M. L. Zepeda-Mendoza, E. Loza-Rubio, E. Rojas-Anaya, M. L. Méndez-Ojeda, C. F. Arias, A. D. Greenwood, The evolution of bat nucleic acid-sensing Toll-like receptors. Mol. Ecol. 24, 5899– 5909 (2015). 26503258
  92. [101]D. J. Castillo, R. F. Rifkin, D. A. Cowan, M. Potgieter, The healthy human blood microbiome: Fact or fiction? Front. Cell. Infect. Microbiol. 9, 148 (2019). 31139578 PMC6519389
  93. [102]F. Rademacher, S. Dreyer, V. Kopfnagel, R. Gläser, T. Werfel, J. Harder, The antimicrobial and immunomodulatory function of RNase 7 in skin. Front. Immunol. 10, 2553 (2019). 31749808 PMC6848066
  94. [103]T. E. Eichler, B. Becknell, R. S. Easterling, S. E. Ingraham, D. M. Cohen, A. L. Schwaderer, D. S. Hains, B. Li, A. Cohen, J. Metheny, S. Tridandapani, J. D. Spencer, Insulin and the phosphatidylinositol 3-kinase signaling pathway regulate Ribonuclease 7 expression in the human urinary tract. Kidney Int. 90, 568– 579 (2016). 27401534 PMC5576060
  95. [104]A. Rodríguez-Carlos, V. Trujillo, I. Gonzalez-Curiel, S. Marin-Luevano, F. Torres-Juarez, A. Santos-Mena, C. Rivas-Santiago, J. A. Enciso-Moreno, V. Zaga-Clavellina, B. Rivas-Santiago, Host defense peptide RNase 7 is down-regulated in the skin of diabetic patients with or without chronic ulcers, and its expression is altered with metformin. Arch. Med. Res. 51, 327– 335 (2020). 32229156
  96. [105]L. M. Bergner, R. J. Orton, A. da Silva Filipe, A. E. Shaw, D. J. Becker, C. Tello, R. Biek, D. G. Streicker, Using noninvasive metagenomics to characterize viral communities from wildlife. Mol. Ecol. Resour. 19, 128– 143 (2019). 30240114 PMC6378809
  97. [106]N. Hecker, V. Sharma, M. Hiller, Transition to an aquatic habitat permitted the repeated loss of the pleiotropic KLK8 gene in mammals. Genome Biol. Evol. 9, 3179– 3188 (2017). 29145610 PMC5716171
  98. [107]V. Sharma, M. Hiller, Loss of enzymes in the bile acid synthesis pathway explains differences in bile composition among mammals. Genome Biol. Evol. 10, 3211– 3217 (2018). 30388264 PMC6296402
  99. [108]N. Mast, A. Saadane, A. Valencia-Olvera, J. Constans, E. Maxfield, H. Arakawa, Y. Li, G. Landreth, I. A. Pikuleva, Cholesterol-metabolizing enzyme cytochrome P450 46A1 as a pharmacologic target for Alzheimer’s disease. Neuropharmacology 123, 465– 476 (2017). 28655608 PMC5546235
  100. [109]V. Sharma, M. Hiller, Increased alignment sensitivity improves the usage of genome alignments for comparative gene annotation. Nucleic Acids Res. 45, 8369– 8377 (2017). 28645144 PMC5737078
  101. [110]V. Sharma, A. Elghafari, M. Hiller, Coding exon-structure aware realigner (CESAR) utilizes genome alignments for accurate comparative gene annotation. Nucleic Acids Res. 44, e103 (2016). 27016733 PMC4914097
  102. [111]H. Cheng, G. T. Concepcion, X. Feng, H. Zhang, H. Li, Haplotype-resolved de novo assembly using phased assembly graphs with hifiasm. Nat. Methods 18, 170– 175 (2021). 33526886 PMC7961889
  103. [112]J. Ghurye, A. Rhie, B. P. Walenz, A. Schmitt, S. Selvaraj, M. Pop, A. M. Phillippy, S. Koren, Integrating Hi-C links with assembly graphs for chromosome-scale assembly. PLoS Comput. Biol. 15, e1007273 (2019). 31433799 PMC6719893
  104. [113]H. Li, R. Durbin, Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 26, 589– 595 (2010). 20080505 PMC2828108
  105. [114]N. Abdennur, L. A. Mirny, Cooler: Scalable storage for Hi-C data and other genomically labeled arrays. Bioinformatics 36, 311– 316 (2020). 31290943 PMC8205516
  106. [115]P. Kerpedjiev, N. Abdennur, F. Lekschas, C. McCallum, K. Dinkla, H. Strobelt, J. M. Luber, S. B. Ouellette, A. Azhir, N. Kumar, J. Hwang, S. Lee, B. H. Alver, H. Pfister, L. A. Mirny, P. J. Park, N. Gehlenborg, HiGlass: Web-based visual exploration and analysis of genome interaction maps. Genome Biol. 19, 125 (2018). 30143029 PMC6109259
  107. [116]W. Shen, S. Le, Y. Li, F. Hu, SeqKit: A cross-platform and ultrafast toolkit for FASTA/Q file manipulation. PLOS ONE 11, e0163962 (2016). 27706213 PMC5051824
  108. [118]A. Rhie, B. P. Walenz, S. Koren, A. M. Phillippy, Merqury: Reference-free quality, completeness, and phasing assessment for genome assemblies. Genome Biol. 21, 245 (2020). 32928274 PMC7488777
  109. [119]P. Danecek, J. K. Bonfield, J. Liddle, J. Marshall, V. Ohan, M. O. Pollard, A. Whitwham, T. Keane, S. A. McCarthy, R. M. Davies, H. Li, Twelve years of SAMtools and BCFtools. Gigascience 10, (2021). PMC7931819 33590861
  110. [120]R. S. Harris, “Improved pairwise alignment of genomic DNA,” thesis, The Pennsylvania State University (2007).
  111. [121]W. J. Kent, R. Baertsch, A. Hinrichs, W. Miller, D. Haussler, Evolution’s cauldron: Duplication, deletion, and rearrangement in the mouse and human genomes. Proc. Natl. Acad. Sci. U.S.A. 100, 11484– 11489 (2003). 14500911 PMC208784
  112. [122]E. Osipova, N. Hecker, M. Hiller, RepeatFiller newly identifies megabases of aligning repetitive sequences and improves annotations of conserved non-exonic elements. Gigascience 8, (2019). PMC6862929 31742600
  113. [123]H. G. Suarez, B. E. Langer, P. Ladde, M. Hiller, chainCleaner improves genome alignment specificity and sensitivity. Bioinformatics 33, 1596– 1603 (2017). 28108446
  114. [124]V. Sharma, P. Schwede, M. Hiller, CESAR 2.0 substantially improves speed and accuracy of comparative gene annotation. Bioinformatics 33, 3985– 3987 (2017). 28961744
  115. [126]V. Ranwez, E. J. P. Douzery, C. Cambon, N. Chantret, F. Delsuc, MACSE v2: Toolkit for the alignment of coding sequences accounting for frameshifts and stop codons. Mol. Biol. Evol. 35, 2582– 2584 (2018). 30165589 PMC6188553
  116. [127]A. Di Franco, R. Poujol, D. Baurain, H. Philippe, Evaluating the usefulness of alignment filtering methods to reduce the impact of errors on evolutionary inferences. BMC Evol. Biol. 19, 21 (2019). 30634908 PMC6330419
  117. [129]A. Dobin, C. A. Davis, F. Schlesinger, J. Drenkow, C. Zaleski, S. Jha, P. Batut, M. Chaisson, T. R. Gingeras, STAR: Ultrafast universal RNA-seq aligner. Bioinformatics 29, 15– 21 (2013). 23104886 PMC3530905
  118. [130]J. T. Robinson, H. Thorvaldsdóttir, W. Winckler, M. Guttman, E. S. Lander, G. Getz, J. P. Mesirov, Integrative genomics viewer. Nat. Biotechnol. 29, 24– 26 (2011). 21221095 PMC3346182
  119. [131]P. Virtanen, R. Gommers, T. E. Oliphant, M. Haberland, T. Reddy, D. Cournapeau, E. Burovski, P. Peterson, W. Weckesser, J. Bright, S. J. van der Walt, M. Brett, J. Wilson, K. J. Millman, N. Mayorov, A. R. J. Nelson, E. Jones, R. Kern, E. Larson, C. J. Carey, İ. Polat, Y. Feng, E. W. Moore, J. V. Plas, D. Laxalde, J. Perktold, R. Cimrman, I. Henriksen, E. A. Quintero, C. R. Harris, A. M. Archibald, A. H. Ribeiro, F. Pedregosa, P. van Mulbregt; SciPy 1.0 Contributors, SciPy 1.0: Fundamental algorithms for scientific computing in Python. Nat. Methods 17, 261– 272 (2020). 32015543 PMC7056644
  120. [132]C. S. Rouk, B. P. Glass, Comparative gastric histology of five North and Central American bats. J. Mammal. 51, 455– 490 (1970). 5530005
  121. [133]H. Park, E. R. Hall, The gross anatomy of the tongues and stomachs of eight new world bats. Trans. Kans. Acad. Sci. 54, 64– 72 (1951).
  122. [135]D. W. Russell, The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72, 137– 174 (2003). 12543708
  123. [137]L. Li, H. Chi, H. Liu, Y. Xia, D. M. Irwin, S. Zhang, Y. Liu, Retention and losses of ultraviolet-sensitive visual pigments in bats. Sci. Rep. 8, 11933 (2018). 30093712 PMC6085362
  124. [138]K. Kries, M. A. S. Barros, G. Duytschaever, J. D. Orkin, M. C. Janiak, D. M. A. Pessoa, A. D. Melin, Colour vision variation in leaf-nosed bats (Phyllostomidae): Links to cave roosting and dietary specialization. Mol. Ecol. 27, 3627– 3640 (2018). 30059176
  125. [139]A. Sadier, K. T. J. Davies, L. R. Yohe, K. Yun, P. Donat, B. P. Hedrick, E. R. Dumont, L. M. Dávalos, S. J. Rossiter, K. E. Sears, Multifactorial processes underlie parallel opsin loss in neotropical bats. eLife 7, (2018). PMC6333445 30560780
  126. [140]B. F. Simoes, N. M. Foley, G. M. Hughes, H. Zhao, S. Zhang, S. J. Rossiter, E. C. Teeling, As blind as a bat? Opsin phylogenetics illuminates the evolution of color vision in bats. Mol. Biol. Evol. 36, 54– 68 (2019). 30476197 PMC6340466

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Authors
Blumer, M., Brown, T., Freitas, M. B., Destro, A. L., Oliveira, J. A., Morales, A. E., Schell, T., Greve, C., Pippel, M., Jebb, D., Hecker, N., Ahmed, A.-W., Kirilenko, B. M., Foote, M., Janke, A., Lim, B. K., & Hiller, M.
Affiliations
  • Goethe University Frankfurt (DE)
  • Max Planck Institute of Molecular Cell Biology and Genetics (DE)
  • Universidade Federal de Viçosa (BR)
  • Senckenberg Research Institute and Natural History Museum Frankfurt/M (DE)
  • Max Planck Institute for the Physics of Complex Systems (DE)
  • Toronto Zoo (CA)
  • Senckenberg Biodiversity and Climate Research Centre (DE)
  • Royal Ontario Museum (CA)
Corresponding author
Hiller, Michael
ORCID
Venue
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Published
2022-03-25
Volume
8
Issue
12
Pages
eabm6494-eabm6494
ISSN
2375-2548 (ISSN-L)
DOI
10.1126/sciadv.abm6494
PMC
PMC8956264
OpenAlex
W4221059947
Cited by
65
References
10
Citations by year
2026: 13 · 2025: 16 · 2024: 19 · 2023: 11 · 2022: 6
FWCI
11.65
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Science Advances (publishedVersion, cc-by-nc)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Lirias (submittedVersion, cc-by-nc)
  • Digital Commons - University of South Florida (University of South Florida) (submittedVersion)
  • Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by-nd)
  • Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by-nc)
Funders
  • Hessisches Ministerium für Wissenschaft und Kunst
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • Max-Planck-Gesellschaft
  • Radboud Universitair Medisch Centrum
  • Max-Planck-Institut für Physik Komplexer Systeme
  • Vlaamse regering
Topics
  • Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Bat Biology and Ecology Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Diptera species taxonomy and behavior
Keywords
Desmodus rotundus, gene loss, blood feeding, dietary adaptation, haplotype-resolved genome, insulin secretion, glycogen metabolism, gastric physiology, bloodborne pathogens, iron excretion, cognitive ability, bat genomics
MeSH terms
Acclimatization, Adaptation, Physiological, Animals, Chiroptera, Diet, Genome

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