(1) Background: Buffaloes are crucial livestock species for food and service in tropical and subtropical regions. Buffalo genetics, particularly in indigenous Chinese breeds such as the Xiangxi white buffalo (XWB), remains an intriguing area of study due to its unique traits and regional significance. (2) Methods: This investigation utilized the whole-genome sequences of twenty XWBs (newly sequenced), along with eighty published whole-genome sequences of other buffalo breeds (including Guizhou white buffalo, river buffalo, and Chinese buffalo in the Yangtze River). Using whole-genome sequencing analysis technology, the population structure, genomic diversity, and selection signatures of XWB were determined. (3) Results: This study revealed that the XWB, being phylogenetically positioned in the middle and lower reaches of the Yangtze River, exhibited substantial genomic diversity. Employing four selection sweep detection methods (CLR, iHS, π-ratio, and FST), several genes were positively identified for adaptive traits in the XWB, including coat color phenotypes (ASIP, KIT), the nervous system (GRIK2), reproduction (KCNIP4), growth and development (IFNAR1, BMP6, HDAC9, MGAT4C, and SLC30A9), the body (LINGO2, LYN, and FLI1), immunity (IRAK3 and MZB1), and lactation (TP63, LPIN1, SAE1). (4) Conclusions: In conclusion, this study enhances our understanding of the genetic distinctiveness and adaptive traits of XWB, highlighting selection signatures crucial for future breeding and conservation and ensuring sustainable use of this vital livestock resource.
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