animals Review Whole-Genome Sequencing and Characterization of Buffalo Genetic Resources: Recent Advances and Future Challenges Saif ur Rehman 1, Faiz-ul Hassan 2, Xier Luo 1, Zhipeng Li 1 and Qingyou Liu 1,* 1 State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning 530005, China; [email protected] (S.u.R.); [email protected] (X.L.); [email protected] (Z.L.) 2 Institute of Animal and Dairy Sciences, Faculty of Animal Husbandry, University of Agriculture, Faisalabad 38040, Pakistan; [email protected] * Correspondence: [email protected] Simple Summary: Recent advancements in high-throughput technologies like whole-genome se- quencing, genome-wide association study (GWAS), gene expression profiling, next-generation se- quencing (RNA and DNA), and genome-wide CHIP-seq scanning are used to detect genetic variants and study gene regulation, gene functioning, and single nucleotide polymorphism (SNP) ordering resources. These techniques offer a wide range of whole-genome data and high coverage to genomic, epigenomic, transcriptomic, and proteomic information related to cellular interactions, functioning, and behavior. In buffaloes, candidate gene studies use the available genetic resources to uncover the functional candidate genes and their interactions associated with buffalo productivity, including pro- duction, adaptation, and disease resistance. Thus, the whole-genome and candidate gene approach to next-generation data could help elucidate the inheritance of complex traits, full genomic coverage, and the genetic dissection of productivity-related attributes, which could ultimately help accelerate Citation: Rehman, S.u.; Hassan, F.-u.; genetic progress in buffaloes. Luo, X.; Li, Z.; Liu, Q. Whole-Genome Sequencing and Characterization of Abstract: The buffalo was domesticated around 3000–6000 years ago and has substantial economic Buffalo Genetic Resources: Recent significance as a meat, dairy, and draught animal. The buffalo has remained underutilized in terms Advances and Future Challenges. of the development of a well-annotated and assembled reference genome de novo. It is mandatory to Animals 2021, 11, 904. https:// explore the genetic architecture of a species to understand the biology that helps to manage its genetic doi.org/10.3390/ani11030904 variability, which is ultimately used for selective breeding and genomic selection. Morphological and molecular data have revealed that the swamp buffalo population has strong geographical genomic Academic Editors: Alfredo Pauciullo diversity with low gene flow but strong phenotypic consistency, while the river buffalo population and Gianfranco Cosenza has higher phenotypic diversity with a weak phylogeographic structure. The availability of recent Received: 11 February 2021 high-quality reference genome and genotyping marker panels has invigorated many genome-based Accepted: 18 March 2021 studies on evolutionary history, genetic diversity, functional elements, and performance traits. The Published: 22 March 2021 increasing molecular knowledge syndicate with selective breeding should pave the way for genetic improvement in the climatic resilience, disease resistance, and production performance of water Publisher’s Note: MDPI stays neutral buffalo populations globally. with regard to jurisdictional claims in published maps and institutional affil- Keywords: buffalo; evolution and domestication; genome sequencing advancement; candidate iations. genes; traits Copyright: © 2021 by the authors. 1. Introduction Licensee MDPI, Basel, Switzerland. The buffalo was domesticated around 3000–6000 years ago and has substantial eco- This article is an open access article nomic significance as a meat, dairy, and draught animal [1–3]. This species is stereotypically distributed under the terms and distributed across wet grasslands, tropical and subtropical forests, swamps, and marshes. conditions of the Creative Commons Though buffaloes are terrestrial mammals, they spend much of their time wallowing in Attribution (CC BY) license (https:// rivers or mud. Wallowing is a comfort behavior that not only helps the animals to keep cool creativecommons.org/licenses/by/ but also protects them from insect bites. Typically, buffaloes are inhabitants of mire holes, 4.0/). Animals 2021, 11, 904. https://doi.org/10.3390/ani11030904 https://www.mdpi.com/journal/animals Animals 2021, 11, 904 2 of 20 Animals 2021, 11, x 2 of 21 rivers, streams, trees, and tall grasses that provide enough food, water, and coverage [2]. Bubalus is thought to have spread from Europe to southern Asia in the Pleistocene epoch, but atoprogressive keep cool but dryalso climateprotects them became from the insect ultimate bites. Typically, reason forbuffaloes contracting are inhabitants its distribution areaof to mire Indonesia, holes, rivers, India, streams, and Southeast trees, and tall Asia. grasses It is that believed provide that enough the buffaloesfood, water, were and brought to Italycoverage from [2]. central Bubalus Europe is thought in the to have 6th centuryspread from or fromEurope the to southern Gulf of TunisAsia in in the the Pleis- 7th century, tocene epoch, but a progressive dry climate became the ultimate reason for contracting its alongdistribution with Arab area conquests. to Indonesia, ThereIndia, and is, however,Southeast Asia. recent It is evidencebelieved that of the the buffaloes introduction of buffaloeswere brought into Africa, to Italy America, from central and Europe Australia in the [61th,3 ].century or from the Gulf of Tunis in theThe 7th worldwide century, along buffalo with Arab population conquests. is T approximatelyhere is, however, 207 recent million evidence heads, of the with in- a distri- butiontroduction of more of thanbuffaloes 200 millioninto Africa, (97%) America, in Asia, and 6.831Australia million [1,3]. (2%) in Africa (predominantly Egypt), 1.449The worldwide million (0.7%)buffalo population in South America, is approximately and less 207 thanmillion 0.144 heads million, with a distri- (0.2%) in Aus- traliabution and of Europe, more than as 200 shown million in (97%) Figure in Asia,1[ 4 ].6.831 Buffaloes million (2%) constitute in Africa a(predominantly littl more than 11.1% Egypt), 1.449 million (0.7%) in South America, and less than 0.144 million (0.2%) in Aus- of the global bovid population, but larger human communities depend on buffaloes for tralia and Europe, as shown in Figure 1 [4]. Buffaloes constitute a littl more than 11.1% of theirthe livelihood global bovid as population, compared but to anylarger other human domesticated communities depend species on [1 buffalo]. Globally,es for their in the last 20 years,livelihood about aas 2% compared annual to increase any otherin domesticated the buffalo species population [1]. Globally, has beenin the observed.last 20 years, Buffaloes contributeabout a about2% annual 13% increase of the globalin the buffalo milk supplypopulation [5]. has Buffalo been observed. milk contains Buffalo aes lower con- amount watertribute but about higher 13% amounts of the global of protein, milk supply fat, [5]. minerals, Buffalo milk and contains lactose a as lower compared amount to cow’s milkwater [2,4]. but higher amounts of protein, fat, minerals, and lactose as compared to cow’s milk [2,4]. Figure 1. Geographical distribution of buffalo population [4]. Figure 1. Geographical distribution of buffalo population [4]. Buffalo milk is considered more suitable for the production of butter, cheese, and otherBuffalo high milk-quality is considereddairy products. more Buffalo suitable meat foris lean the with production lower cholesterol of butter, and cheese, fat con- and other high-qualitytents than dairybeef and products. comparatively Buffalo better meat taste is lean[2]. In with waterlogged lower cholesterol conditions, andlike rice fat contents thanpaddy beef andfields, comparatively buffaloes are considered better tastesuperior [2]. draught In waterlogged animals and conditions,have been frequently like rice paddy fields,used buffaloes for ploughing are considered and can drag superior heavier loads draught than other animals cattle. and Furthermore, have been their frequently hide used for ploughingis quite useful and in mak caning drag a variety heavier of leather loads products than other [2,4]. cattle. Buffalo Furthermore,manure is used theiras a hide is natural fertilizer, which supplements the soil with organic matter and essential elements quite useful in making a variety of leather products [2,4]. Buffalo manure is used as a and successfully reduces the need for chemical fertilizers. Most importantly, in villages, naturalthe small fertilizer, farmers which and poor supplements people prefer the to soilrear b withuffaloes organic owing matter to their andstrong essential ability to elements and successfully reduces the need for chemical fertilizers. Most importantly, in villages, the small farmers and poor people prefer to rear buffaloes owing to their strong ability to efficiently use low-quality and less digestible roughage than other ruminants, which makes them easy to raise on locally available crop residues. Additionally, buffaloes are considered lucrative assets and ready cash, particularly for landless and smallholder families [6]. Animals 2021, 11, 904 3 of 20 Buffaloes are a comparatively resilient and thrifty animal, but it is also vulnerable to parasites and diseases that affect cattle, including tuberculosis, piroplasmosis, brucellosis, trypanosomiasis, and rinderpest