Genetic Analysis Of High Altitude Adaptability Of Bange Cashmere Goat In Tibet

Molecular mechanism of high altitude adaptation for plateau mammals has been one of the hotresearch topics for researchers all over the world. It is of significant importance in the protection andutilization of the excellent livestock and poultry resources, the development of livestock farming, andthe diagnosis and treatment of plateau diseases. Bange Cashmere goat (BG) is the unique local varietiesat high altitudes after long-term natural selection and artificial domestication, having the good ability toadapt to low pressure, low oxygen, and cold weather in high altitude area, also forming a stable geneticability in high altitude environments. However, the molecular mechanism for high altitude adaptation isunclear. This study investigated the molecular genetic mechanism for high altitude adaptation of BangeCashmere goat from several aspects, the blood physiological characteristics of the goats from differentaltitudes, the transcriptome research, HIF-1gene characteristics, and exons capture research of the goats.The main content is as follows:Blood physiological and biochemical values from Bange Cashmere goat and Liaoning Cashmere goatat different altitudes were determined. The results showed that the mean corpuscular hemoglobin(MCH), serum albumin (ALB), blood urine nitrogen (BUN), and aspartate transaminase (AST) ofBange Cashmere goat were significantly higher than those in Liaoning Cashmere goat (P<0.01). Thewhite blood cell (WBC) and mean corpuscular hemoglobin concerntration (MCHC) of Bange Cashmeregoat were higher than those in Liaoning Cashmere goat (P<0.05). These phenotypic characteristics ofblood reflect that the contents of several components in the blood were regulated by Bange Cashmeregoat to adapt to high altitude. These phenotypic characteristics were closely associated with adaptivegenome evolution, laying the foundations for molecular mechanisms for high altitude adaptation ofBange Cashmere goat at the molecular evolution level.The single nucleotide polymorphisms (SNPs) in transcriptomes of Bange Cashmere goat andLiaoning Cashmere goat were identified using RNA sequencing technology (RNA-Seq). Thetranscriptome sequencing was conducted on Illumina Hiseq2000platform for11pooled tissues,including cerebral cortex, bronchus, skin, heart muscle, lung, liver, gall-bladder, spleen, kidney, marrow, andskeletal muscle. After alignment with the goat genome,53,800intra-specific putative SNPs in the BangeCashmere goat sequence assembly,60,738intra-specific putative SNPs in the Liaoning Cashmere goatsequence assembly, and5,391inter-specific SNPs between Bange Cashmere goat and LiaoningCashmere goat were identified. In addition, transcriptomes were also assembled using de novo strategy.The reads unmapped to the goat genome were aligned to the contig sequence from the de novo assembly.The alignment showed that the hidden8,178intra-specific putative SNPs and7,727intra-specificputative SNPs, probably caused by alternative splicing, were found in Bange Cashmere goat contigsequence and Liaoning Cashmere goat contig sequence, respectively. Furthermore, several cashmeregrowth related genes (FGF12, FGF14, BMPR-IA, MTR, MT2, BMP2K, GHR, and GH2), high-altitudeadaptation related genes (EPAS1, PTEN, CDH13, GNPAT, FOXO1, HLA-DRA, and RHOB), and11HIF-1signal pathway related genes (HIF1A, EGLN1, PTEN, PIK3CA, PIK3C2A, PIK3CB, PIK3CG, PIK3R1, CPKC, CAMK2, and IL6R) were identified after GO classification and KEGG pathwayanalysis.Comparison to the genome of Capra hircus, six SNPs were identified in HIF1A gene of Bangecashmere goat, including A463G, G1074A, T1467C, C1738T, G1989A, and G2377A. Of them, A463Gcaused an amino acid mutation, I155V, which made the secondary structure and spatial structure ofHIF1A of Bange Cashmere goat different from that of Capra hircus’s (JN897021). The increaseddistances between amino acids79and155(from26.583to31.205), amino acids80and158(from17.396to23.566) of HIF1A of Bange Cashmere goat make it easier to form a dimer with HIF1B toenhance the transcription of the genes involving in the oxygen transportation, growth, and metabolismunder the high altitude hypoxia environments.On the basis of the above results, four additional breeds of goat living in the different altitude regions,which are Rutog goat (RT, altitude4750m), Chaidamu goat (CD, altitude2980m), Nanjiang Cashmeregoat (NJ, altitude1700m), and Inner Mongolia Cashmere Goat (IM, altitude1500m), were selected toscan coding SNPs (cSNPs) in the genome using exome capture and DNA pooling sequencingtechnology. The potential45470SNPs for BG,46501for RT,53971for CD,48704for NJ,57444forIM, and39180for LN were screened, respectively. After neutral test, the unique1,260genes for BGwere identified, which were mainly classified in the GO terms: multicellular organismal process(GO:0032501), sensory perception of light stimulus (GO:0050953), ion transport (GO:0006811),response to oxygen radical (GO:0000305), ion homeostasis (GO:0055072), and regulation of I-kappaBkinase/NF-kappaB cascade (GO:0043122and GO:0043123).These results demonstrated that under thenatural and artificial selection, Bange Cashmere goat accumulated mutations in the genome in responseto high altitude hypoxia and strong ultraviolet environments and the mutation of the the genome ofBange Cashmere goat increased its adaptability to the high altitude environments.