Genetic Variation And Environmental Adaptation Of Indicine Cattle Genome

The domestication of aurochs has resulted in two distinct but interbreeding subspecies of cattle: humpless taurine cattle(Bos taurus taurus)and humped indicine cattle(Bos taurus indicus).Taurine cattle were estimated to be domesticated ～10,000 years before present(BP)in Southwest Asia and ～8,000 years BP in South Asia.Indicine cattle are mainly distributed in semi-arid,subtropical and tropical humid areas such as South Asia,Southeast Asia,East Asia,Africa and America.Indicine cattle were crucial to the development of local agricultural lifestyles and economies,shaping modern civilizations in subtropical and tropical regions.Research on the origin and domestication of indicine cattle has made some progress.However,little is known about the genetic relationships among Asian indicine populations,especially the indicine genetic resources along the migration route of Southern China,Southeast Asia,and South Asia.In particular,the genetic relationships between East Asian indicine and South Asian indicine cattle remain unclear.By analyzing 354 indicine samples from 57 breeds around the world,this study revealed the unique genetic characteristics and phylogeographical patterns of the autosomal,Y chromosome and mitochondrial genomes of indicine cattle from the whole genome level,explored the discontinuous pattern of indicine genome diversity,and identified potential candidate genes for indicine adaptation to the local extreme environment.The contribution of gene introgression of wild Bos species to genetic diversity and environmental adaptation of East Asian indicine was further revealed.The main results obtained in this study are as follows:1.By comparing the genome-wide variation,the worldwide indicine cattle fell into three geographic subgroups:(1)South Asian indicine;(2)African indicine cattle mixed with African taurine cattle;(3)East Asian indicine that may have undergone several interbreeding events with other wild and/or domesticated cattle breeds.Based on Y chromosome SNP,two indicine paternal ancestors(Y3A and Y3B)and 7 subhaplotype groups(Y3A1,Y3A2,Y3A3,Y3B1,Y3B2,Y3B3 and Y3B4)were identified.Three indicine mt DNA haplotypes(I1,I2 and I3)were identified based on mitochondrial genome variation.High paternal and maternal genetic diversity strongly supports South Asia as the sole center of Bos indicus domestication.The combined uniparental and autosomal data support a coastal route for the first migration wave to Southeast Asia as the main entry point of indicine cattle into East Asia.2.By comparison with taurine cattle,it was found that there were highly differentiated genomic regions between indicine and taurine cattle.A total of 156 common selected regions including 117 candidate genes were identified in the indicine populations.The strongest signal related to heat tolerance and immunity of indicine cattle is located on Chr7,including genes DNAJC18,HSPA9,MATR3,MZB1 and STING1.The other two strongly selected regions,located on Chr1 and Chr19,were mainly associated with hair growth(LIPH),cardiac growth(CAMTA2),and antiviral immunity(SPAG7).These genes may play an important role in protecting indicine cattle from extreme heat and solar radiation.Selected genes related to growth traits(PUS7,RARS2 and RINT1),muscle development(MLC1 and GMPPB),immune system(DDIT3,DCTN2,DTX4,MST1 and IL9R)and malaria resistance(GYPB)were detected in South Asian cattle.These results suggest that hormone regulation and immune system play important roles in the adaptation of South Asian cattle to semi-arid environment.Specific selected regions in East Asian indicine,such as those related to host immune and lung cancer(SEMA3B,GNAI2,SEMA3 F,RBM5,MST1 R and MON1A),thermal avoidance behavior(TRPA1),photoperiodism(EYA3)and circannual clock(FAM204A),which may be related to the adaptation to local environment.3.The genetic diversity of East Asian indicine cattle is very high.Approximately 0.29%to 4.26% and 0.61% to 2.78% of banteng and gaur genome introgression were retained in East Asian indicine cattle.Adaptive introgression analysis has shown that introgression genes are involved in environmental adaptation,nervous system,endocrine system and other biological processes,including water transport(ILDR1),blood homeostasis(CASR),dermatosis(CSTA),oxygen transport(HBM,HBA,HBA1 and HBQ1).It is speculated that the introgression of these genes may contribute to the local adaptation of indicine in the tropical humid climate of southern East Asia.4.In order to further explore the genetic variation of East Asian cattle,the genome of Hainan cattle was assembled at chromosome level.At the same time,the Mongolian genome was assembled as a control,and a total of 123,898 structural variants(SV)were identified using genome alignment and 18 long sequencing reads data.Several SVs detected from long reads are in exons of genes associated with epidermal differentiation(CRNN and SBSN),skin barrier(SPINK5),and bovine tuberculosis resistance(SPN).Functional investigations showed that a 108-bp exonic insertion in SPN may affect the uptake of Mycobacterium tuberculosis by macrophages by increasing the number of O-linked glycosylation sites,which might contribute to low susceptibility of Hainan cattle to bovine tuberculosis.Genotyping in 373 whole genome sequences from 39 breeds by short-read sequencing identified 2,610 SVs that were differentiated along a north–south gradient in China,involving 862 genes,many of which were enriched in pathways related to environmental adaptation(corrected P < 0.05).We identified 1,457 Chinese indicine-stratified SVs that possibly originated from banteng,among which a 316-bp intronic deletion in DDX58 was frequent in Chinese indicine cattle.In conclusion,this study conducted a genome-wide systematic assessment of indicine resources distributed around the world,reconstructed the phylogenetic and evolutionary history of indicine cattle,and revealed the genetic variation basis of environmental adaptability of East Asian indicine from the perspective of SNP and SV,providing scientific basis for the protection of Chinese indicine breed resources and new breed breeding,which has great theoretical and practical significance.