Whole Genome Sequencing of the Dzo: Genetic Implications for High Altitude Adaptation, Sterility, and Milk and Meat Production

The Dzo, a hybrid between the domestic Yak and cattle found on the Qinghai-Tibetan plateau are commercially important owing to increased meat and milk production, as well as their adaptation to extremely high-altitude environments. To better understand the genomic architecture and adaptive capabilities of this unique domesticated hybrid, we performed whole genome resequencing and compared the genomic architecture and variation of the Dzo to its progenitors: the cattle and Yak. In total, 33.17 M single nucleotide variations (SNVs) were detected between the Dzo and cattle reference genomes. Even though the Dzo is known to be sterile, no genetic signatures associated with sterility were found on the Dzo Y chromosome. On the contrary, our results suggest that the autosomal DMC1 locus (Chromosome 5. 110729098. C>CT) plays a role in the sterility of Dzo, which warrants further exploration of its functions. We integrated the whole genome resequencing data of cattle and Yak to obtain candidate genes with a high degree of variation that might be associated with altitudinal adaptation. We found that the EPAS1 gene, which encodes hypoxia-inducible factor 2α, exhibited significant variation (Chromosome 11.28664187 C>T) between Yak and cattle, and may play a key role in the genetic basis of altitudinal adaptation. In addition, in analyzing differences between the Dzo, Yak, and cattle genomes, we uncovered several additional genomic signatures relevant to high altitude adaptation and meat and milk production. These findings underscore the need for further studies to improve ruminant stock for sustainable agriculture on the Qinghai-Tibet plateau..

Dzo Sığırlarında Tüm Genom Sekanslaması: Yüksek Rakıma Adaptasyon, Sterilite İle Süt ve Et Verimine Etkisi

Evcil Yak ile Qinghai-Tibet platosunda bulunan sığırın bir hibriti olan Dzo artmış et ve süt üretimi ile birlikte aynı zamanda oldukça yüksek rakımlı bölgelere adaptasyonu nedeni ile ticari olarak önem arz etmektedir. Bu özgün evcil hibritin genomik yapısını ve uyum kapasitelerini daha iyi anlamak amacıyla tüm genom sekanslaması yapılarak genomik yapısı ve varyasyonlar Dzonun progenitörleri olan sığır ve Yak ile karşılaştırıldı. Dzo ile sığır referans genomları arasında toplam 33.17 M tek nükleotid varyasyonu belirlendi. Dzo steril olarak bilinmesine rağmen Dzo Y kromozomunda sterilite ile ilgili hiç bir genetik işarete rastlanmadı. Aksine, elde edilen bulgular otozomal DMC1 lokusunun (Kromozom 5. 110729098. C>CT) Dzonun sterilitesinde rol oynadığına işaret etmekte ve bu nedenle de daha ileri araştırılmaların yapılması gerekmektedir. Yüksek rakıma adaptasyon ile ilişkili yüksek oranda varyasyona sahip genlerin araştırılması amacıyla sığır ve Yakın tüm genom sekanslama verilerinin entegrasyonu gerçekleştirildi. Hipoksi ile indüklenebilir faktör 2α’yı kodlayan EPAS1 geni Yak ve sığır arasında yüksek varyasyon (Kromozom 11.28664187 C>T) göstermekteydi ve bu nedenle yüksek rakıma adaptasyonun genetik temelinde rol oynayabileceği düşünüldü. Ayrıca, Dzo, Yak ve sığır genomları arasındaki farklılıklar analiz edildiğinde, yüksek rakıma adaptasyon ile birlikte et ve süt üretimine etki eden bazı ilave genomik işaretlere rastlandı. Bu bulgular Qinghai-Tibet platosunda daha ileri ve devam ettirilebilir ruminant yetiştiriciliği için daha fazla çalışmalara ihtiyaç olduğunu göstermektedir

___

Axelsson E, Ratnakumar A, Arendt ML, Maqbool K, Webster MT, Perloski M, Liberg O, Arnemo JM, Hedhammar A, Lindblad-Toh K: The genomic signature of dog domestication reveals adaptation to a starch-rich diet. Nature, 495 (7441): 360-364, 2013. DOI: 10.1038/nature11837

Rubin CJ, Zody MC,  Eriksson J,  Meadows JR,  Sherwood E, Webster MT, Jiang L, Ingman M, Sharpe T, Ka S, Hallböök F, Besnier F, Carlborg O, Bed’hom B, Tixier-Boichard M, Jensen P, Siegel P, Lindblad-Toh K, Andersson L: Whole-genome resequencing reveals loci under selection during chicken domestication. Nature, 464 (7288): 587-591, 2010. DOI: 10.1038/nature08832

Decker JE, Mckay SD,  Rolf MM, Kim J, MolinaAA, Sonstegard TS, Hanotte O, Götherström A, Seabury CM, Praharani L, Babar ME, Correia de Almeida Regitano L, Yildiz MA, Heaton MP, Liu WS, Lei CZ, Reecy JM, Saif-Ur-Rehman M, Schnabel RD, Taylor JF: Worldwide patterns of ancestry, divergence, and admixture in domesticated cattle. PLOS Genet, 10:e1004254, 2014. DOI: 10.1371/ journal.pgen.1004254

Hou JX, An XP, Song YX, Wang JG, Ma T, Han P, Fang F, Cao BY: Combined effects of four SNPs within goat PRLR gene on milk production traits. Gene, 529, 276-281 2013. DOI: 10.1016/j.gene.2013.07.057

Wilkanowska A, Mazurowski A, Mroczkowski S, Kokoszynski D: Prolactin (PRL) and prolactin receptor (PRLR) genes and their role in poultry production traits. Folia Biol, 62, 1-8, 2014. DOI: 10.3409/fb62_1.1

Sanchez JE, Perera E, Baumbach L, Cleveland WW: Growth hormone receptor mutations in children with idiopathic short stature. J Clin Endocrinol Metab, 83, 4079-4083, 1998. DOI: 10.1210/jcem.83.11.5238

Sandor C, Li W, Coppieters W, Druet T, Charlier C, Georges M: Genetic variants in REC8, RNF212, and PRDM9 influence male recombination in cattle. PLOS Genet, 8:e1002854, 2012. DOI: 10.1371/journal.pgen.1002854

Binz SK, Sheehan AM, Wold MS: Replication protein A phosphorylation and the cellular response to DNA damage. DNA Repair, 3, 1015-1024, 2004. DOI: 10.1016/j.dnarep.2004.03.028

Bachtrog D: Signs of genomic battles in mouse sex chromosomes. Cell. 159, 716-718, 2014. DOI: 10.1016/j.cell.2014.10.036

Chang TC, Yang Y, Retzel EF, Liu WS: Male-specific region of the bovine Y chromosome is gene rich with a high transcriptomic activity in testis development. Proc Nat Acad Sci USA, 110, 12373-12378, 2013. DOI: 10.1073/ pnas.1221104110

Cortez D, Marin R, Toledoflores D, Froidevaux L, Liechti A, Waters PD, Grützner F, Kaessmann H: Origins and functional evolution of Y chromosomes across mammals. Nature, 508, 488-493, 2014. DOI: 10.1038/nature13151

Qi X, Han J, Wang G, Rege JE, Hanotte O: Assessment of cattle genetic introgression into domestic Yak populations using mitochondrial and microsatellite DNA markers. Anim Genet, 41, 242-252, 2010. DOI: 10.1111/j.1365-2052.2009.01989.x

Soulé ME: Heterozygosity and developmental stability: another look. Evolution, 33, 396-401, 1979. DOI: 10.1111/j.1558-5646.1979.tb04693.x

Xiao Z, Wang K, Wang L, Yang Y, Ni Z, Xie X, Shao X, Han J, Wan D, Qiu Q: Genome-wide patterns of copy number variation in the Chinese Yak genome. BMC Genom, 17: 379, 2016. DOI: 10.1186/s12864-016-2702-6

Qiu Q, Wang L, Wang K, Yang Y, Ma T, Zhang X, Ni Z, Hou F, Long R, Abbott R, Lenstra J, Liu J: Yak whole-genome resequencing reveals domestication signatures and prehistoric population expansions. Nat Commun, 6: 10283, 2015. DOI: 10.1038/ncomms10283

Smathers RL, Petersen DR: The human fatty acid-binding protein family: Evolutionary divergences and functions. Human Genom, 5, 170-191, 2011. DOI: 10.1186/1479-7364-5-3-170

Chmurzynska A: The multigene family of fatty acid-binding proteins (FABPs): Function, structure and polymorphism. J Appl Genet, 47, 39-48, 2006. DOI: 10.1007/BF03194597

Zechner R, Kienesberger PC, Haemmerle G, Zimmermann R, Lass A: Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores. Jf Lipid Res, 50, 3-21, 2009. DOI: 10.1194/jlr.R800031-JLR200

Newman JH, Holt TN, Cogan JD, Womack B, Phillips JA 3rd, Li C, Kendall Z,  Stenmark KR,  Thomas MG,  Brown RD,  Riddle SR,  West JD,  Hamid R: Increased prevalence of EPAS1 variant in cattle with high-altitude pulmonary hypertension. Nat Commun, 6: 6863, 2015. DOI: 10.1038/ncomms7863

Ikeda J, Kaneda S, Kuwabara K, Ogawa S, Kobayashi T, Matsumoto M, Yura T, Yanagi H: Cloning and expression of cDNA encoding the human 150 kDa oxygen-regulated protein, ORP150. Biochem Biophysic Res Commun, 230, 94- 99, 1997. DOI: 10.1006/bbrc.1996.5890

Lorenzo FR, Huff  C, Myllymäki M, Olenchock B, Swierczek S, Gordeuk V, Wuren T, Ri-Li G, McClain DA, Khan TM, Koul PA, Guchhait P, Salama ME, Xing J, Semenza GL, Liberzon E, Wilson A, Simonson TS, Jorde LB, Kaelin WG Jr, Koivunen P, Prchal JT: A genetic mechanism for Tibetan high-altitude adaptation. Nat Genet, 46, 951-956, 2014. DOI: 10.1038/ng.3067

Berra E, Benizri E, Ginouvès A, Volmat V, Roux D, Pouysségur J: HIF prolylhydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. EMBO J, 22, 4082-4090, 2003. DOI: 10.1093/emboj/ cdg392

Yi X, Liang Y, Huerta-Sanchez E, Jin X, Cuo ZXP, Pool JE,  Xu X,  Jiang H,  Vinckenbosch N,  Korneliussen TS,  Zheng H,  Liu T,  He W,  Li K,  Luo R, Nie X, Wu H, Zhao M, Cao H, Zou J, Shan Y, Li S, Yang Q, Asan, Ni P, Tian G,  Xu J,  Liu X,  Jiang T,  Wu R,  Zhou G,  Tang M,  Qin J,  Wang T,  Feng S,  Li G,  Huasang,  Luosang J,  Wang W,  Chen F,  Wang Y,  Zheng X,  Li Z,  Bianba Z, Yang G, Wang X, Tang S, Gao G, Chen Y, Luo Z, Gusang L, Cao Z, Zhang Q, Ouyang W, Ren X, Liang H, Zheng H, Huang Y, Li J, Bolund L, Kristiansen K,  Li Y,  Zhang Y,  Zhang X,  Li R,  Li S,  Yang H,  Nielsen R,  Wang J,  Wang J: Sequencing of 50 human exomes reveals adaptation to high altitude. Science, 329, 75-78, 2010. DOI: 10.1126/science.1190371

Huerta-Sanchez E, Jin X, Bianba Z, Peter BM, Vinckenbosch N, Liang Y, Yi X, He M, Somel M, Ni P, Wang B, Ou X, Huasang, Luosang J, Cuo ZX, Li K, Gao G, Yin Y, Wang W, Zhang X, Xu X, Yang H, Li Y, Wang J, Wang J, Nielsen R: Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA. Nature, 512, 194-197, 2014. DOI: 10.1038/nature13408

Berg IL, Rita N,  Lam KG,  Shriparna  S, Linda OH, May CA,  Jeffreys AJ: PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans. Nat Genet, 42, 859-863, 2010. DOI: 10.1038/ng.658

Baudat F, Buard J, Grey C, Fledel-Alon A, Ober C, Przeworski M, Coop G, de Massy B: PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice. Science, 327, 836-840, 2010. DOI: 10.1126/science.1183439

Soh YQ, Alföldi J, Pyntikova T,    Brown LG,   Graves T, Minx PJ,  Fulton RS,  Kremitzki C,  Koutseva N,  Mueller JL,  Rozen S,  Hughes JF,  Owens E,  Womack JE,  Murphy WJ,  Cao Q,  de Jong P,  Warren WC,  Wilson RK,  Skaletsky H,  Page DC: Sequencing the mouse Y chromosome reveals convergent gene acquisition and amplification on both sex chromosomes. Cell, 159, 800-813, 2014. DOI: 10.1016/j.cell.2014.09.052

Tang H, Peng J, Wang P, Risch NJ: Estimation of individual admixture: analytical and study design considerations. Genet Epidemiol, 28, 289-301, 2005. DOI: 10.1002/gepi.20064 20. Bellott DW, Hughes JF, Skaletsky H,  Brown LG,  Pyntikova T, Cho TJ, Koutseva N, Zaghlul S, Graves T, Rock S, Kremitzki C, Fulton RS, Dugan S, Ding Y, Morton D, Khan Z, Lewis L, Buhay C, Wang Q, Watt J, Holder M, Lee S, Nazareth L, Alföldi J, Rozen S, Muzny DM, Warren WC, Gibbs RA, Wilson RK,  Page DC:  Mammalian Y chromosomes retain widely expressed dosagesensitive regulators. Nature, 508, 494-499, 2014. DOI: 10.1038/nature13206

Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S: MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol, 28, 2731-2739, 2011. DOI: 10.1093/molbev/msr121

Kumar P, Henikoff S, Ng PC: Predicting the effects of coding nonsynonymous variants on protein function using the SIFT algorithm. Nat Protoc, 4, 1073-1081, 2009. DOI: 10.1038/nprot.2009.86

Chen K, Wallis JW, Mclellan MD, Larson DE, Kalicki JM, Pohl CS, McGrath SD, Wendl MC, Zhang Q, Locke DP, Shi X, Fulton RS, Ley TJ, Wilson RK, Ding L, Mardis ER: BreakDancer: An algorithm for high-resolution mapping of genomic structural variation. Nat Methods, 6, 677-681, 2009. DOI: 10.1038/nmeth.1363

Van der Auwera GA, Carneiro MO, Hartl C, Poplin R, Del Angel G, LevyMoonshine A, Jordan T, Shakir K, Roazen D, Thibault J, Banks E, Garimella KV, Altshuler D, Gabriel S, DePristo MA: From fastQ data to high confidence variant calls: The genome analysis toolkit best practices pipeline. Curr Protoc Bioinformatics, 43 (11): 11.1-33, 2013. DOI: 10.1002/0471250953.bi1110s43

DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, Philippakis AA, del Angel G, Rivas MA, Hanna M, McKenna A, Fennell TJ, Kernytsky AM, Sivachenko AY, Cibulskis K, Gabriel SB, Altshuler D, Daly MJ: A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet, 43, 491-498, 2011. DOI: 10.1038/ng.806

Li H1, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R; 1000 Genome Project Data Processing Subgroup: The genome analysis toolkit: A mapreduce framework for analyzing next-generation DNA sequencing data. Genom Res, 20, 1297-1303, 2010. DOI: 10.1101/gr.107524.110

Li H, Handsaker B, Wysoker A, Fennell T, Ruan J: The sequence alignment/map format and SAMtools. Bioinformatics, 25, 2078-2079, 2009. DOI: 10.1093/bioinformatics/btp352

Li H, Durbin R: Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics, 25, 1754-1760, 2009. DOI: 10.1093/bioinformatics/ btp324

Zimin AV, Delcher AL, Florea L, Kelley DR, Schatz MC, Puiu D, Hanrahan F, Pertea G, Van Tassell CP, Sonstegard TS, Marçais G, Roberts M, Subramanian P, Yorke JA, Salzberg SL: A whole-genome assembly of the domestic cow, Bos taurus. Genom Biol, 10:R42, 2009. DOI: 10.1186/gb-2009-10-4-r42

Bolger AM, Lohse M, Usadel B: Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics, 30, 2114-2120, 2014. DOI: 10.1093/bioinformatics/ btu170

Wang K, Hu Q, Ma H, Wang L, Yang Y, Luo W, Qiu Q: Genome-wide variation within and between wild and domestic Yak. Mol Ecol Resour, 14, 794-801, 2014. DOI: 10.1111/1755-0998.12226

Daetwyler HD, Capitan A, Pausch H, Stothard P, van Binsbergen R, Brøndum RF, Liao X, Djari A, Rodriguez SC, Grohs C, Esquerré D, Bouchez O, Rossignol MN, Klopp C, Rocha D, Fritz S, Eggen A, Bowman PJ, Coote D, Chamberlain AJ, Anderson C, VanTassell CP, Hulsegge I, Goddard ME, Guldbrandtsen B, Lund MS, Veerkamp RF, Boichard DA, Fries R, Hayes BJ:: Whole-genome sequencing of 234 bulls facilitates mapping of monogenic and complex traits in cattle. Nat Genet, 46, 858-865, 2014. DOI: 10.1038/ng.3034

Qiu Q, Zhang G, Ma T, Qian W, Wang J, Ye Z, Cao C, Hu Q, Kim J, Larkin DM, Auvil L, Capitanu B, Ma J, Lewin HA, Qian X, Lang Y, Zhou R, Wang L, Wang K, Xia J, Liao S, Pan S, Lu X, Hou H, Wang Y, Zang X, Yin Y, Ma H, Zhang J, Wang Z, Zhang Y, Zhang D, Yonezawa T, Hasegawa M, Zhong Y, Liu W, Zhang Y, Huang Z, Zhang S, Long R, Yang H, Wang J, Lenstra JA, Cooper DN, Wu Y, Wang J, Shi P, Wang J, Liu J: The Yak genome and adaptation to life at high altitude. Nat Genet, 44, 946-949, 2012. DOI: 10.1038/ng.2343

Cheviron ZA, Brumfield RT: Genomic insights into adaptation to highaltitude environments. Heredity. 108, 354-361, 2012. DOI: 10.1038/hdy.2011.85

Luo XL, Song HF, Guan JQ: Investigation on mechanism of sterility of male hybrids between Yak and cattle. J Appl Anim Res, 42 (4): 395-399, 2014. DOI: 10.1080/09712119.2013.875907

Tumennasan K, Tuya T, Hotta Y, Takase H, Speed RM, Chandley AC: Fertility investigations in the F1 hybrid and backcross progeny of cattle (Bos taurus) and yak (B. grunniens) in Mongolia. Niigata J Healt Welfare, 78 (1): 69-73, 1997. DOI: 10.1159/000134633

Anand IS, Harris E, Ferrari R, Pearce P, Harris P: Pulmonary haemo-dynamics of the Yak, cattle, and cross breeds at high altitude. Thorax, 41 (9): 696-700, 1986. DOI: 10.1136/thx.41.9.696

Medugorac I, Graf A, Grohs C, Rothammer S, Zagdsuren Y, Gladyr E, Zinovieva N, Barbieri J, Seichter D, Russ I, Eggen A, Hellenthal G Brem G, Blum H, Krebs S, Capitan A:  Whole-genome analysis of introgressive hybridization and characterization of the bovine legacy of Mongolian Yaks. Nat Genet, 49 (3): 470-475. 2017. DOI: 10.1038/ng.3775
Kafkas Üniversitesi Veteriner Fakültesi Dergisi-Cover
  • ISSN: 1300-6045
  • Yayın Aralığı: Yılda 6 Sayı
  • Başlangıç: 1995
  • Yayıncı: Kafkas Üniv. Veteriner Fak.
Sayıdaki Diğer Makaleler

Bir Kedide Lipid-Laden Humor Aquosus

Elgin Orçum UZUNLU, Mustafa ARICA, Kurtuluş PARLAK

Bir Buzağıda Clostridium perfringens Tip E Nedenli Enterotoksemi Olgusu

Mehmet ÇALICIOĞLU, Burak KARABULUT, Hasan ABAYLI, Hatice EROKSUZ, Yesari EROKSUZ, Canan AKDENİZ İNCİLİ, Baris OTLU

Whole Genome Sequencing of the Dzo: Genetic Implications for High Altitude Adaptation, Sterility, and Milk and Meat Production

Jingcheng ZHONG, Zhijie MA, Zhixin CHAI, Hui WANG, Chengfu ZHANG, Qiumei JI, Jinwei XIN

Kolombiya, Cordoba’daki Köpeklerde Babesia spp.

Jorge MIRANDA, Salim MATTAR, Carmen GALVÁN, Juan BALLUT

Türkiye’den 12 Yerli, Karagül, Karacabey Merinosu ve Anadolu Yaban Koyununda (Ovis gmelinii anatolica) Y-Kromozom Polimorfizmleri

Evren KOBAN BAŞTANLAR, Arif PARMAKSIZ, Emel ÖZKAN ÜNAL, Ahmet OYMAK, Füsun ÖZER, İnci TOGAN, Sevgin DEMİRCİ, Eren YÜNCÜ

Laktasyon Döneminde Karbofurana Maruz Kalan Yavru Farelerde (Mus musculus) Beyin Hücreleri Ölümü

Muhammad Luqman Ali BAHOO, Lita Rakhma YUSTINASARI, Widjiati WIDJIATI

Evaluation of Genotoxic Effects of C60 Fullerene-γ-Fe2O3 and MultiWall Carbon Nanotubes-γ-Fe2O3 Nanoparticles

ÖZLEM DEMİRCİ TURGUNBAYER, NESRİN HAŞİMİ, ERSİN KILINÇ, VEYSEL TOLAN

Türkiye’de Atlarda anti-Anaplasma phagocytophilum Antikorlarının İlk Tespiti

Tülin GÜVEN GÖKMEN, Armağan Erdem ÜTÜK, Melis ZEYBEK, Elçin GÜNAYDIN, Selçuk PEKKAYA, Fatih KUZUGÜDEN

Acute Erosive Gastritis Due to Pine Processionary Caterpillar Setae Ingestion in a Dog (Bir Köpekte Çam Kese Böceği Setalarının Yenilmesine Bağlı Akut Eroziv Gastritis)

DİDEM PEKMEZCİ, Zeynep Nurselin KOT, ÜMİT ÖZCAN

Brain Cells Death on Infant Mice (Mus musculus) Caused by Carbofuran Exposure During the Lactation Period

Muhammad Luqman Ali BAHOO, Widjiati WIDJIATI, Lita Rakhma YUSTINASARI