Signatures of positive selection for local adaptation of African native cattle populations: A review

Wondossen AYALEW,WU Xiao-yun,Getinet Mekuriaw TAREKEGN,CHU MinLIANG Chun-nianTesfaye SISAY TESSEMAYAN Ping

1 Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau,Ministry of Agriculture and Rural Affairs/Key Laboratory of Yak Breeding Engineering,Lanzhou Institute of Husbandry and Pharmaceutical Sciences,Chinese Academy of Agricultural Sciences,Lanzhou 730050,P.R.China

2 Department of Animal Production and Technology,Wolkite University,Wolkite P.O.Box 07,Ethiopia

3 Institute of Biotechnology,Addis Ababa University,Addis Ababa P.O.Box 1176,Ethiopia

4 Scotland’s Rural College (SRUC),Roslin Institute Building,University of Edinburgh,Edinburgh EH25 9RG,United Kingdom

Abstract Cattle are central to the lives and diverse cultures of African people. It has played a crucial role in providing valuable protein for billions of households and sources of income and employment for producers and other actors in the livestock value chains. The long-term natural selection of African cattle typically signals signatures in the genome,contributes to high genetic differentiations across breeds. This has enabled them to develop unique adaptive traits to cope with inadequate feed supply,high temperatures,high internal and external parasites,and diseases. However,these unique cattle genetic resources are threatened by indiscriminate cross-breeding,breed replacements with exotic cosmopolitan breeds,and climate change pressures. Although there are no functional genomics studies,recent advancements in genotyping and sequencing technologies have identified and annotated limited functional genes and causal variants associated with unique adaptive and economical traits of African cattle populations. These genome-wide variants serve as candidates for breed improvement and support conservation efforts for endangered cattle breeds against future climate changes. Therefore,this review plans to collate comprehensive information on the identified selection footprints to support genomic studies in African cattle to confirm the validity of the results and provide a framework for further genetic association and QTL fine mapping studies.

Keywords: adaptive trait,African cattle,production traits,reproduction traits

1.Introduction

The tropical region covers approximately 36% of the world’s land surface. These areas are characterized by rainforest and savannah environments that cover a wide range of landscapes and are known for high biodiversity,including many exotic pests and diseases (Juoet al.2003;Barendse 2017). In the tropics,cattle populations provide various products and services for the people. They play a pivotal role in providing valuable protein for billions of rural and urban households,and serve as sources of income and employment for producers and other actors in the value chains (Herreroet al.2013;Marshallet al.2019). African cattle breeds have evolved over centuries and demonstrate a large phenotypic and genetic diversity,and this helped them to develop unique adaptive features to resist poor feed availability,high temperature,and high prevalence of internal and external parasite and disease challenges (Mirkenaet al.2010;Mwaiet al.2015).These animals are mainly kept in smallholder farms and subjected to natural and non-systematic artificial selection for economic traits. The detection of selective signatures in the genome is an essential step for guiding sustainable breed improvement to meet the current production need in various environments,particularly in light of changing environment (Fernandezet al.2005),and is essential to facilitate sustainable utilization and conservation of threatened and endangered livestock breeds (McFarlaneet al.2006;Dalvitet al.2008).

In recent decades,the demand for animal-source food has increased rapidly in the developing countries due to population growth,rapid urbanization,income growth,and shifts in diet (Delgado 2005;Thornton 2010).Sufficient genetic variation in livestock populations is a prerequisite to develop resilience to climate change and fulfilling the ever-changing consumer demands (Biscariniet al.2015). Evaluating available genetic variation is a crucial step to understand the genetic potential,which provides breeders with a tool for reliable selection decisions and conservation. To date,advances in highthroughput sequencing and SNP genotyping technologies and parallel progress in statistical techniques have allowed identifying genes and useful mutations linked with ecologically and economically important traits (Edeaet al.2015;Saravananet al.2021). Identifying genomic regions affected both by artificial selection and climate adaptation could help to understand how changes at the genome level modulate changes in phenotype,which holds high promises to improve animal breeding processes for production,health and welfare (Cesaraniet al.2018;Johnsson 2018). Although we have begun to understand the molecular basis of African cattle genomic architectures,the molecular basis of adaptation and agroeconomic traits are still poorly understood. Recent studies of targeted and genome-wide selection signatures from African cattle population provide some insights into the mechanisms of natural and artificial selection and uncover functional genes and pathways related to adaptive and agro-economic traits. These selection footprints are suit to implement and provide a new perspective of genetic improvement in the breeding goals.

Previously,quantitative trait loci (QTL) mapping of cattle population were carried out by using low density multi-allelic markers (i.e.,microsatellites) that have low detection power of genome-wide variations in complex traits (Zhanget al.2012). To date,following the discovery of variants (SNPs) with immense coverage in the genome,the positive signature variants together with the phenotype and pedigree information are assisting the implementation of genome wide association study (GWAS)for the detection of genes and regulatory elements with better resolution and confidence interval for the traits of interest. Moreover,genomic selection has revolutionized genetic progress by direct analyzing causal mutation for non routinely recorded economic traits (i.e.,feed efficiency,carcass and meat quality,and tick resistance)and a drastic reduction in generation intervals (Meuwissenet al.2013). However,there is still a dearth of African cattle comprehensive reviews on the molecular bases of adaptive and agro-economic traits. Therefore,this review provides insights on the efforts made on detection of positive signatures in tropically adapted cattle populations which can subsequently be used to implement genomic selection for improved cattle production and productivity,and resilience in the diverse tropical environment.

2.Selection signatures in African cattle genome

African cattle breeds have evolved over centuries and demonstrate a large phenotype and genetic diversities,and thus help them to adapt a wide range of environment.In the current climate change scenario,African livestock husbandry faces several challenges,such as increase in temperature and atmospheric carbon dioxide,along with variable precipitation. The interaction of these circumstances affected pasture composition,forage and water availability (Palmeret al.2008;Rojas-Downinget al.2018),and the expansion of livestock pests and diseases (Anyambaet al.2009;Nyangiweet al.2018).Given numerous challenges including limited access to adequate nutrition and disease management,poor institutional capacities,and lack of adequate government policies and funding to develop the livestock sector,the productivity of African cattle is still less than optimal(Ibeagha-Awemuet al.2019). There has been a positive attempt at balancing selection objectives and composite populations (crossbred) to combine adaptation and productivity traits suited to the available environmental resources,socio-economic,and cultural conditions (Regeet al.2011;Bunninget al.2019). Thus,identifying the genetic basis,disease resistance,and better production traits of local cattle breeds/stocks that are well adapted to extreme environments offers great opportunities to develop suitable breeding programs to meet the growing demand for livestock products at an unprecedented rate of climate change (Lobellet al.2008;Regeet al.2011).

To cope with multiple challenges and build climateresilient livestock systems,a composite strategy involving the use of old science in different and innovative ways,and the strategic use of new technologies to understand and address problems is indispensable (Regeet al.2011). The ongoing developments of high-throughput genotyping and whole genome sequencing facilities,coupled with the rapid development of statistical methods and bioinformatics pipelines,have enabled the detection of genomic variants associated with adaptive and agroeconomic traits. The recent detection of genome-wide selective traits in African cattle herds has provided insights into natural and artificial selection mechanisms and identified genes and pathways associated with adaptive and agro-economic traits. Interestingly,these signatures provide a realistic procedure for defining genetic variations and assisting the selection of superior genotypes with higher breeding value for adaptive and agro-economic traits to support the livelihood of resourcepoor smallholder farmers and future breeding companies.

2.1.Positive signature of selection for local adaption in indigenous cattle in African

The adaptation of animals to different environments is typically shaped by structural and functional genomic variations (Zwaneet al.2021). Understanding the genetic basis of adaptive mechanisms to extreme environments is essential for conserving and improving local cattle breeds under future climate change scenarios and variable production objectives. Populations in different parts of the world show greater adaptation to their local agroclimatic conditions than exotic breeds (Rashamol and Sejian 2018). The African cattle populations have been subjected to harsh environmental pressures,including hot,dry,or humid tropical climate conditions and severe and diverse disease challenges (Kimet al.2017). Longterm natural and human selection have driven different patterns of genomic variation between these cattle populations,which has helped them develop various tropical environmental adaptations (Mwaiet al.2015;Tayeet al.2018). For example,zebu cattle are known for their superior adaptation to harsh environments,that includes resistance to various types of disease and parasites,as well as thermo tolerance (Bahbahaniet al.2015,2018b;Kimet al.2017;Tayeet al.2018). Furthermore,African cattle populations are characterized by low nutrient requirements for maintenance and excellent walking ability which allows them to walk long distances in search of grazing and water to survive under poor quality feed and watering conditions (Mirkenaet al.2010;Tayeet al.2018). Exploring the characteristics of positive selection is now one of the main interests of animal geneticists,as it can be used to identify genes that regulate phenotypic changes,which hold great promise for developing breeding strategies for better production,health and welfare (Zhaoet al.2015;Johnsson 2018). Although there is limited availability of molecular data for African cattle,the development of statistical,bioinformatics and modeling tools allows the identification of genes linked to adaptive phenotypes of African cattle breeds (Fig.1;Table 1).

Table 1 Candidate genes underlying selection signatures of African cattle breeds to tropical environment stress adaptations

Heat toleranceHeat stress is one of the major challenges that impair production and reproductive performance,metabolic and health status,and immune response of animals (Mentaet al.2022). Although they have poor productivity,African cattle breeds have developed heat tolerance mechanisms of lowered metabolic rates and an increased capacity to lose heat due to their experience with chronic heat stress for an extended period (Hansen 2004;Paula-Lopeset al.2013;Mwaiet al.2015). The heat stress response is a complex adaptation that integrates many anatomical,physiological,biochemical,and molecular components (Guptaet al.2013;Paula-Lopeset al.2013). Morphological adaptations are physical changes in animals develop over many generations and improve their survival ability in a specific environment. Such adaptation mechanisms to heat stress are mainly affected by hair coat characteristics such as coat color,hair length,higher density of sweat glands,slender legs,and less subcutaneous fat (Gaughanet al.2019). The higher density of sweat glands and smoother and shinier hair coat in zebu cattle helps to better regulate body temperature and cellular function during heat stress (Hansen 2004). For example,animals with light/white coats are thought to be more beneficial in hot tropical climates since they reflect 50 to 60% of direct solar radiation compared to darkcolored animals (McManuset al.2009). Cattle adapted to arid environments have smooth,short,and thin hair,which helps to dissipate heat. Furthermore,animals in warmer climates have sweat glands that are larger in width,volume,perimeter,and density (Sejianet al.2018). Physiological adaptability is the modification of the metabolic response to cope with extreme environmental conditions. The increase in respiration and pulse rate,rectal temperature,skin temperature,and sweating rate are some of the physiological factors which help to maintain homeostasis in animals (Indu and Pareek 2015).Moreover,decreased dry matter intake and altered water metabolism of tropical cattle are physiological responses to heat stress that adversely affect their production and reproduction.

Fig. 1 Schematic representation of indigenous African cattle (Bos indicus and African taurus) adaptive attributes to tropical environmental stresses.

It is widely acknowledged that the thermotolerance mechanisms of African cattle breeds have evolved genes and pathways that potentially contribute to greater tolerance attributes. For instance,complementary statistical methods (Hp,iHS,Rsb,XP-CLR and XP-EHH)identified heat shock protein gene families (HSPB9,HSPA4,HSPA9,HSPA6andHSPH1) that have played an important role in the response to heat stress (Bahbahaniet al.2015,2017,2018b;Makinaet al.2015;Kimet al.2017;Zwaneet al.2019;Ben-Jemaaet al.2020). The differential expression of these protein families betweenindicineandtaurinecattle signifies unique adaptive features of African zebu in the tropics (Gautieret al.2009). Moreover,heat shock factors (HSFs) are the transcription factors that regulate the expression of the heat shock proteins under thermal stress (Tayeet al.2017a,b,c;Bahbahaniet al.2018b;Paguemet al.2020).It is also interesting to note that the protein phosphatases genes (PPP3CA,PPP2R5EandPPP4R3B) were detected in N’Dama cattle that modulate the proteins activities in a cell,often in response to external heat stimuli (Tayeet al.2017a,b,c). In general,these African cattle-specific selective sweeps are evidence of shared historical selection footprints and introgression,most likely due to their ancestral,geographical,and husbandry system acquaintances for resilience to the tropics. This may also reflect the pleiotropic effects of genes on other relevant adaptive and agro-economic traits.

The higher density of sweat glands of African zebu is regulated by positively selected heat stress resistance genes (Table 1).ITPR2is a protein-coding gene that encodesInsP3Rthat helps calcium ions move into and out of cells during heat stress (Tayeet al.2017a,b,c). It promotes the release of calcium from the extracellular interstitial fluid and the release of intracellular Ca2+stores necessary for normal sweat production (Klaret al.2014;Cui and Schlessinger 2015). Coat colors are easily identifiable phenotypes that play an important role in heat tolerance. The pre-melanosome (PMEL) is one of the candidate genes linked to eumelanin synthesis and may therefore regulate the coat color in the small East African shorthorn zebu and Butana cattle (Bahbahaniet al.2015).The melanogenesis genes (SLC45A2andATRN) that regulate hair color were identified in African zebu using XP-CLR and XP-EHH statistical tests (Tayeet al.2017a,b,c). These unique genomic regions have a role of shaping the color characteristics of African cattle population that result in enhancing conductive and convective heat loss and reduce absorption of solar radiation in tropical conditions. However,the efforts of detection of positive selection need to be supported by further transcriptome profiling and fine mapping studies to validate the signatures observed in the candidate genomic regions.

Resistance to trypanosomosisTrypanosomosis is one of the endemic parasitic diseases that affect cattle and other wide range of hosts in sub-Saharan Africa (Biyazenet al.2014). The disease results in the loss of livestock and agricultural productivity with severe socioeconomic and public health impacts (Madalcho 2019). The significant consequences of infection include mortality,loss of body condition,abortion,and agalaxia (Troncyet al.1981). Although the use of trypanocidal drugs and vector management has a positive outcome,both control methods have been shown to be not sustainable (Paling and Dwinger 1993). Furthermore,the low efficacy of the available trypanocidal drug,a faster rate of drug resistance,and the slight hope of vaccine developments necessitates the exploitation of trypanotolerance cattle breeds (d’Ieterenet al.1998). Thus,using tolerant breeds in a breeding system reduces or eliminates the use of chemicals to control the trypanosomosis vector and contributes to ecosystem health (Smetkoet al.2015). However,most cattle in Africa are susceptible to the disease and some indigenous taurine cattle populations have evolved a tolerance to trypanosomiasis termed trypanotolerance (Murray and Dexter 1988).In Africa,17% of cattle populations are distributed in areas with higher tsetse challenges,of which only 6%are trypanotolerant breeds (Agyemang 2005). Longhorntaurine(N’Dama) and short-horntaurine(Lagune,Baoule,Muturu,and Namchi) and a short-horntaurine(Sheko) from east Africa are known cattle breeds for their ability to cope with trypanosome infections (Smetkoet al.2015;Bahbahaniet al.2018a;Tijjaniet al.2019;Paguemet al.2020). Their trypanotolerant phenotypes have been linked to their innate capacity to control the level of parasitemia and anemia (Murrayet al.1984). Consequently,trypanotolerant African breeds are expected to have unique genomic signatures with respect to their distinct phenotypes. However,despite the multiple burdens of diseases and parasite infections,trypanotolerant cattle populations are threatened by indiscriminate cross-breeding,which demands due attention.

Anemia is a significant clinical sign of the advancement of trypanosome infection;therefore,genes involved in regulating iron transport and homeostasis represent interesting candidates (O’Gormanet al.2009).The recent study by Mekonnenet al.(2019) identified the candidate genes (MIGA1,CDAN1,HSPA9,andPCSK6)associated with the evolutionary response against anemia in Sheko cattle. The mitoguardin 1 (MIGA1)gene is an important regulator of the development and proliferation of lymphocytes during inadequate iron uptake that plays an important role in the formation of anemia immunity (Rouault 2006). The codanin-1(CDAN1) gene is another candidate gene involved in the process of erythropoiesis and play a key role in the organization of heterochromatin during the division of these developing cells. ThePCSK6gene regulates iron homeostasis as a result of iron deficiency anemia(Guillemot and Seidah 2015). Bahbahaniet al.(2018a)also identified the genesLTA4H,IL7,IL15,FCN,LTA4HandNFAM1as potential targets of natural selection related to immunity in Sheko cattle. Another important candidate gene related to anemia isGFI1B. This gene modulates erythropoiesis for the expansion and differentiation of erythroid progenitors. The influence ofGFI1Bon erythropoiesis could be related to the trypanotolerance of west Africantaurine(Muturu) cattle(Tijjaniet al.2019). An XP-EHH test detected potential selective sweeps (STOM,SLC40A1,andCOMMD1)that are fixed (or nearly fixed) for intensively studied trpanotolerant west Africantaurine(N’Dama) (Kimet al.2017;Tayeet al.2017a,b,c).SLC40A1is a cell membrane protein involved in iron export from duodenal epithelial cells. It gives instructions for making a protein called ferroportin,and this protein mediates the process of iron absorption and delivery into the bloodstream(Theurlet al.2016). The Copper metabolismMURR1domain protein 1 (COMMD1) is a protein involved in multiple cellular pathways,including copper homeostasis,NF-κB,and hypoxia signaling (Vonket al.2014). Nuclear factor kappaB (NF-kappaB) signaling influences innate and adaptive immunity,inflammation,B-cell development,lymphoid organogenesis,and stress response. Malfunctioning of this gene is associated with marked accumulation of copper in hepatocytes (Smedleyet al.2009),adversely affecting iron absorption and transport (Da Silvaet al.2009). Another microsatellite study identified theCXCR4gene for trypanotolerance in multiple west African taurine (Dayoet al.2009). It plays an important role in the haematopoiesis,development,and organization of immune systems. Although the value of native cattle breeds are overlooked,the use of indigenous breeds coupled with context-specific breeding plans are often the best strategies for sustainable benefit from the indigenous cattle genetic resources in Africa. In fact,the positive footprint of Africantaurinesfor both heat and trypano challenges makes them a strong candidate for multifaceted cattle improvement in the complex conditions of the African continent. Furthermore,these unique signatures allowed us to directly target candidate genes and candidate variants that were then added to the customized chip used for routine genomic evaluation of African cattle breeds.

Resistance to tick and tick-borne diseasesTicks are essential ectoparasites that cause significant economic and health losses in farm animals. These ectoparasites impacted about 80% of the world’s cattle population,either directly by the effect of their bites or by the infectious agents they transmit (Eskezia and Desta 2016;Hurtado and Giraldo-Ríos 2018). Babesiosis,bartonellosis,and anaplasmosis are the main parasitic diseases transmitted by ticks and have caused serious economic losses to cattle production worldwide (Eskezia and Desta 2016).Africa’s hot and humid climate is a suitable habitat for tick survival (Eskezia and Desta 2016),and this causes annual losses of 160 million due to ticks and tick-borne diseases (Olwochet al.2008). Despite multiple attempts to control tick-borne diseases,chemical control has been found to be ineffective and requires a high cost. As a result,habitat management,host genetic selection,and the development of resistance breeds are a means of preventing tick infestation (Shymaet al.2015). Zebu cattle have greater tick resistance manifested by their perpetual exposure to the infected zone or by morphological differences (i.e.,skin thickness,coat type,coat color,hair density,and skin secretions) (Meltzer 1996;Fosteret al.2007;Gasparinet al.2007). Furthermore,despite the complexity of the tick-host interaction,host resistance to ticks is known to be under genetic control. To further elucidate the potential genetic mechanisms underlying tick resistance,different studies demonstrated specific genomic alterations toward tick resistance (Table 1). In this regard,the bovine lymphocyte antigen (BOLA) gene is the major histocompatibility complex,and plays an important role in antigen processing and presentation. It was identified as an important immune response gene that regulates tick resistance in African cattle (Kimet al.2017;Tayeet al.2018). Furthermore,TNF alpha induced protein 8 like 3(TNFAIP8L3) and solute carrier family 25 member 48 (SLC25A48) genes have also been reported in African cattle breeds in relation to tick resistance(Makinaet al.2015;Tayeet al.2018).

Skin is the largest organ of vertebrates and the target of infestation and feeding by more than 15 000 species of hematophagous arthropods (Franzinet al.2017). The structure of epidermal layers and cattle skin color are the major defenses against ectoparasite invasion (e.g.,tick)(Gautieret al.2009;Mapholiet al.2014). Interestingly,keratin genes are heteropolymeric structural proteins that form the structural framework of skin and hair cells and secrete cytokines that initiate local inflammatory responses to tick resistance (Nakamuraet al.2013). In epidermal transglutaminases (TGM1andTGM3) gene regions,two novels (10:20736590and10:20739046)and three known missense variants (rs41695720,rs136283113andrs211468449) were identifiedin African zebu (Tayeet al.2018). These Ca2+dependent crosslinking enzymes regulates apoptosis and cornification of the epidermis;this provides a defense function against ectoparasites (Kongsuwanet al.2010). Furthermore,Tayeet al.(2018) have elucidated that theSLC45A2andMATPgenes were found to modulate melanogenesis in a specialized cell called melanocytes. These strong signals in relation to morphological traits (e.g.,skin thickness,hair cells,and color-patterning traits) are consistent with the theory of the ‘domestication syndrome’ in mammals,suggesting that selective pressure for ectozoan during the initial stages of domestication involved the development of dermal cell populations and led to multiple structural changes shared by various species of domesticated animals. This could result in the shared light coat color of most African indicine cattle breeds (Marufuet al.2011).Interestingly,it might support the hypothesis that ticks on light-colored cattle can be easily seen by predator birds and picked up easily,eventually contributing to their resistance to tick-born problems (Mapholiet al.2014). Indeed,the continent is endowed with huge genetically diversified cattle breeds,however,genomic studies toward identifying the genomic loci related to tick resistance are limited. Therefore,further studies should be conducted on a comprehensive endemic ectoparasite resistance of indicine cattle breeds.

Drought toleranceThe African continent is subjected to severe recurrent droughts,resulting in scarcity of natural resources,poor quantity and quality of forages,high prevalence of livestock diseases and parasites,as well as water shortages (Masihet al.2014;Dzavoet al.2019). Cattle have already succumbed to several climate-driven distresses,including massive deaths,loss of body condition,and reduced productivity (Kimaroet al.2018;Dzavoet al.2019). Despite these severe challenges,local cattle breeds have evolved several coping mechanisms compared to exotic cattle from the northern hemisphere exposed to the same environment.Long exposure to poor nutritional quality and seasonal availability of feed exerts strong selective pressure on tropical cattle to lower their metabolic rates and increase digestive efficiency for low quality feedstuffs in the tropics (Mirkenaet al.2010;Tayeet al.2018). Hegarty(2004) indicated that the higher protozoal population in the rumen ofBosindicuscattle has a faster rate of digestion to ferment nitrogen-deficient poor-quality feed thanBostauruscattle. This may be expected to reduce the production of methane and the ruminal long chain of fatty acid synthesis for the production of energy from low-quality diets. However,the lower metabolic rate of African cattle resulted in reduced feed intake,milk yield,thyroid hormone secretion,and growth,making them lower in performance compared totaurinebreeds of European descent (Paguemet al.2020). Recent technological and analytical advances in genomics open a new avenue for identifying genomic regions that harbor resilience in the scarcity of feed resources. Several candidate genes and gene families associated with the adaptive response to scarce and low-quality feed have been selected in African cattle (Tayeet al.2017a,b,c;Tijjaniet al.2019). For example,the hypocretin receptor 1 gene (HCRTR1) is a G-protein coupled receptor involved in the regulation of feeding behavior identified in west African longhorntaurine(N’Dama) (Kimet al.2017).Growth hormone 1 (GH1) has been identified as a positive selection for the limited food supply. ElevatedGH1gene expression induces a physiological response to nutritional deprivation as a consequence of important seasonal fluctuations in feed availability for North African cattle (Ben-Jemaaet al.2020). Furthermore,a whole genome sequence study has identified candidate genes(MAP3K5andZRANB3)related to feed efficiency/residual feed intake of African cattle breeds (Tijjaniet al.2019).Mitogen-activated protein kinase kinase 5 (MAP3K5)is a member of a family of enzymes involved in kinase signaling cascades in the cell. It plays an important role in cell differentiation and survival,apoptosis,and innate immune response,and is a candidate marker for residual feed intake in pig (Puet al.2016) and beef cattle (Ser?oet al.2013). These genes selected for the scarce feed supply have led to the specialization of breeds of cattle for feeding efficiency. It might be expected that breeds with the same characteristics would show a similar picture of selection sweeps related to such specialization.Conversely,divergently specialized breeds would share few selection sweeps. However,it is an open secret that most cattle populations on the African continent are in extensive production conditions challenged by feed scarcity,which forced them to evolve many shared selection signals. These evolved footprints play a significant role directly or indirectly in response to feeding scarcity in drought-prone seasons and arid and semi-arid cattle production areas in the continent. The putative genomic regions regulating the efficient utilization of feed resources in African cattle are summarized in Table 1.

2.2.Selection signatures associated with milk production and compositions traits

Dairy production in Africa plays a fundamental role in the region’s economic and sustainable development.It contributes to food security,combats malnutrition,and provides employment and income to millions of smallholder farm families. Milk production and composition are the most economically important traits that affect dairy cattle profitability (Nanaeiet al.2020). Dairy farmers in the tropics regions face many challenges,including poor performance of local breeds,disease pressure,poor feed availability,high temperatures,and generally inappropriate management conditions (Cheruiyotet al.2018). Furthermore,most of the production in the tropics,particularly in Africa and Asia,takes place in smallholder systems,which are characterized by small herd sizes,lack of performance and pedigree recording,as well as the lack of standard genetic evaluation systems (Kosgey and Okeyo 2007).Despite these constraints,genome sequencing of African cattle populations is already underway for several native and composite breeds. These genomic data will enable the development of African cattle-specific genomic tools that may be used in genome-wide selective breeding and genetic evaluation (Mwaiet al.2015).

Both environmental and genetic variables regulate milk production and compositional qualities. The kappa casein (CSN3) gene is associated with milk fat and protein percentage. It has a significant influence on milk processing properties in comparison to other casein variants. Genetic polymorphisms in the bovineCSN3gene have been linked to milk yield traits (milk yield,fat yield,and protein yield) (Nanaeiet al.2020) and composition traits (fat and protein percentages) in African cattle breeds (Ahmedet al.2017).ABCG2andLAP3are another shared genes between exotic and African cattle breeds (Tijjaniet al.2019). Positive selection of these genes is associated with better milk production,fat,and protein yield. The beta 1,4-galactosyltransferase(B4GAL-T1) gene is atrans-Golgi resident enzyme that regulates the lactose biosynthesis in mammals and is a candidate for milk production traits (Table 2). This gene modulates milk production traits,including milk,lactose,protein,and total solids production (Shahbazkiaet al.2012;Nanaeiet al.2020). Although many genes and functional pathways for milk production traits are widely identified and annotated in commercial dairy breeds,selection signals in indicine cattle breeds are limited.High within-breed genetic variations coupled with limited signal for milk production traits are a reflection of less artificial selection pressure on local cattle breeds. Over the years,African cattle dairy improvement programs have focused on crossbreeding of local cattle with exotic breeds that allow the exploitation of heterosis in economic traits. In particular,its success rate remains ineffective and most dairy farmers in the tropics faced comparativelychallenging genotype and environmental interactions.However,the long-term effort on tropical cattle (e.g.,Brazilian-Gir) showed exemplary genetic potential for dairy production and a relevant option for dairying in the tropics (Reweet al.2015). Therefore,the untapped potential of African cattle populations coupled with the a proper breeding plan is a promising approach to the development of tropical dairy production.

Table 2 Candidate genes underlying milk production and composition traits of indigenous African cattle breeds

2.3.Selection signatures associated with meat traits

Meat and meat products are the most valuable livestock products as the main sources of high-quality protein for human consumption. Cattle are one of the most important livestock species and make up the majority of the meat consumed by humans. In sub-Saharan Africa,about 150 breeds of native cattle and recently introduced exotic and commercial mixed cattle are recognized (Rege 1999;Mwaiet al.2015). Over the years,natural selection has established a collection of breeds known to adapt to harsh conditions and has specific beef characteristics. African Sanga cattle are an intermediate type of cattle believed to be the result of interbreeding betweenBostaurusandBos indicus(Rege and Tawah 1999;Mwaiet al.2015),which has better carcass and meat quality attributes thanBos taurusandBosindicusbreeds (Strydomet al.2000,2008,2011). Although there are several indigenous beef cattle breeds with good beef production capability,this potential remains untapped since a strategic breeding plan for genetic improvement is rare in this region (Reweet al.2009). Furthermore,unlike the developed world,much of the African cattle improvement research and development work profoundly emphasized crossbreeding to increase milk production. Even with little success,the breeding plan consistently overlooked local cattle breeds,and this makes local cattle remain poor non-specialized breeds.However,few attempts contributed to the possibility of improving beef production in sub-Saharan Africa. For example,large-scale ranching was established in semiarid areas of Kenya for the improvement of Kenyan Boran primarily for commercial beef production (Reweet al.2009),and pure breeding and cross-breeding of Nguni and the Afrikaner cattle with exotic counterparts in South Africa (Scholtz and Theunissen 2010;Abinet al.2016). A review by Rios Utrera and Van Vleck (2004)showed that most meat production and quality traits have moderate heritability;therefore,improving these traits using conventional techniques remains a challenge. To date,in addition to the estimation of genetic parameters with pedigree data,advances in molecular technology have resulted in the identification of DNA markers of farm animal species,and this has created a new avenue for identifying genes and quantitative trait loci (QTL) regions used for genomic selection (Van Marle-K?steret al.2013).

Skeletal muscle is a major tissue providing lean tissues for meat animals. Therefore,understanding the genes and candidate genes that regulate skeletal muscle development is essential for improving animal growth and meat production efficiency. Interestingly,genes and QTL related to anatomical development were identified in the East African short-horn zebu (e.g.,LEMD3,LOXandRXFP2). These genes are important to maintain optimal growth and development (Bahbahaniet al.2017).LEMD3andLOXare associated with the development of different organs,such as the heart (LEMD3),lung and blood vessels (LOX) (Makiet al.2005). A whole genome study identifiedCAPZB,COL9A2,PDGFRA,MAP3K5,ZNF410,LIMA1andPKM2genes that can affect muscle structure and development,thereby affecting meat tenderness in Ankole cattle (Tayeet al.2017a,b,c). Indeed,meat traits are controlled by many genes and environmental factors.Measurement of these traits is difficult and expensive to measure until late in life or after the animal has been harvested. Hence,uncovering these genomic regions can be used as ideal candidates to achieve higher genetic gains through genomic selection compared to traditional pedigree-based evaluations.

Meat quality is a complex and multifactorial trait modulated by genetics and environmental factors (Listratet al.2016). The important quality traits for fresh meat are pH,color,water holding capacity,texture,and amount of fat (intramuscular fat/marbling). At the same time,tenderness,flavor,and juiciness are the main eating quality traits of cooked meat. A genome-wide scan by Tayeet al.(2017a,b,c) identified several candidate genes that regulate the biological mechanisms of beef quality characteristics in Ankole cattle (Table 3). For example,CAPZB,COL9A2,PDGFRA,MAP3K5,ZNF410,andPKM2genes are involved in muscle structure and metabolism that affect meat tenderness.PLA2G2A,PARK2,ZNF410,MAP2K3,PLCD3,PLCD1andROCK1genes are related to intramuscular fat that regulate adipose metabolism and adipogenesis (Tayeet al.2017a,b,c). Although there are no African cattle-specific candidate genes,it can be concluded that the identified pathways and genes can be used as genetic markers in the custom chip for routine genomic evaluation of African cattle breeds.

Table 3 Candidate genes underlying meat traits of African cattle breeds

Table 4 Candidate genes underlying reproductive traits selection signatures of African cattle

2.4.Selection signatures associated with fertility traits

The general productivity and adaptability of cattle depend greatly on reproductive performance in a particular environment. Despite many achievements of classical animal breeding,extensive selection for milk production traits has led to a decline in female fertility in dairy cattle arising from an unfavorable correlated selection response (Kadarmideenet al.2003;Jorjani 2006). The decline in reproductive performance could affect culling rates and herd life and reduce the genetic gain from production traits. In response to such deterioration in fertility traits,genetic selection has been suggested to play a myriad role in cost-effective,cumulative,and permanent improvements of cattle fertility (Wallet al.2003). Consequently,recent access to bovine whole genome sequence and high-density SNP panels has provided remarkable resources to understand the effects of domestication and artificial selection on the underlying genetic variation that contributes to phenotypic diversity(Randhawaet al.2016).

Several studies shed light on candidate genes associated with cattle fertility and located in several genomic regions under the selection sweep. For instance,the recent selection in steroid 5-alpha reductase 3 gene (SRD5A3) was detected by iHS statistical method that regulates the development of the male reproductive system (Bahbahaniet al.2018b). This gene converts testosterone to dihydrotestosterone to maintain differentiation of the prostate and external genitalia.Relaxin/insulin-like family peptide receptor 2 (RXFP2)is another candidate gene that modulates testicular descent development in zebu and native Africantaurine(Bahbahaniet al.2015,2017,2018b). It is speculated that the candidate genes (OR6C4andOR2AP1) are involved in the guide of sperms towards oocytes during fertilization via the interaction with various chemo-attractants secreted by the oocyte-cumulus complex (Bahbahaniet al.2015).A positive selection on the relaxin family peptide receptor 2 (RXFP2) is also identified to modulate higher fertility and semen quality in zebu cattle under tropical conditions(Hansen 2004;Bahbahaniet al.2018b;Tijjaniet al.2019). In addition,the strong selection ofIGF-1gene modulates follicular development and oocyte maturation(Tayeet al.2018).ESR2is also a protein-coding gene that controls many cellular processes,including growth,differentiation,and function of the reproductive system,and it has suggested modulating sperm quality traits (Tayeet al.2018). In fact,many genes essential for fertility traits are shared within the germinal organs of both sexes characterized by low heritability. Strong selection signals in these populations can be a starting point to shed light on the definite genomic selection toward high-fertility phenotypes.

3.Challenges and future implications

African livestock breeds are enormous and diverse and typically well adapted to the harsh environmental conditions under which they perform (Marshallet al.2019). Despite their unique features,most indigenous livestock breeds are characteristically low in production and productivity. Improvements and conservation of these local breeds are a prerequisite for meeting projected human needs and resilience to an uncertain future (FAO 2015). For more than half a century,crossbreeding has been principally applied in the tropics to exploit breed complementarities. Specifically,specialized exotic breeds have been crossed with indigenous breeds to combine the high productivity of cosmopolitan exotic breeds with the adaptive attributes of African zebu. Unfortunately,the unplanned and indiscriminate crossbreeding practices of most African countries have accelerated the threat of extinction of local cattle breeds (Rege 1999;Rege and Gibson 2003). The prevalence of livestock disease,adverse climatic conditions,and nutritional challenges are additional limiting factors in tropical livestock breeding.Furthermore,the conventional method used for centuries of genetic evaluations is not robust as it lacks routine recording of reliable phenotypes and analytical tools to synthesize the data,providing timely feedback to help improve farmer management and husbandry techniques(Mrodeet al.2019). Thus,detecting polymorphisms in genes that may influence economically important traits and adaptive attributes is crucial for the current management/improvement programs. Although indigenous African cattle are relatively less intensively studied at the genome level,the rapid developments and cost reduction of sequencing technologies provide limited insight into African cattle genetic diversity,admixture level and signals of selection (Kimet al.2017,Tayeet al.2017a,b,c;Bahbahaniet al.2018b;Tijjaniet al.2019;Zwaneet al.2019). However,the large majority of these signature studies were focused on genomic regions under positive selection rather than balanced selection.So,a genome scan for loci under balancing selection is essential to reveal functionally important genes that are difficult to detect using common reverse or forward genetics due to weak or indirect phenotypic effects.

Another recurring problem was the genome coverage of low-density markers imply that the alleles with lowfrequencies may be undetected,in which they may be omitted from such arrays. Recently advances in highdensity markers and whole genome sequence resolved the ascertainment bias associated with low-density arrays.However,all genomic tools (i.e.,the reference genome and commercial SNP chips) in African cattle genomic studies were still developed with little or no information from African cattle populations (Mwaiet al.2015;Marshallet al.2019). African cattle are more distant from the available cattle reference genome (EuropeanBostaurus,i.e.,UMD3.1andARS-UCD1.2) (Mwaiet al.2015;Paguemet al.2020). Comparison/mapping of African cattle genomic sequence with existing reference genome results in false positive signatures and eventually distort future genomic breeding decision. As a result,ade novogenome assembly of indigenous African cattle is essential to discover new SNPs inclusion in existing SNP assays and develop custom-made SNP chips for adjusting ascertainment bias in genome-wide selective breeding of local cattle breeds. Given genomic selection is more likely to have a profound effect on cattle improvements,a large number of phenotyped and genotyped individuals are necessary to obtain accurate genomic breeding values (Goddard and Hayes 2009). However,phenotypic information is usually more expensive and difficult to obtain than genotypic information,particularly as the cost of genotyping declines (Biscariniet al.2015). Written pedigree records are lacking in most small-holder farms in developing countries,making it almost impossible to make informed breeding decisions.

The measurement of an increasingly large array of new phenotypes (Houleet al.2010),and the development of systems for automatic trait measurement and recording are a powerful tool to improve both herd management and successful breeding schemes (Berryet al.2012). In addition,the sustainability of breeding programs based on traditional or genomic approaches requires a strong government attention to develop enabling policies and regulatory frameworks that encourage public-private partnerships (Mrodeet al.2019). Building human capacity in animal breeding,genetics,and genomics within Africa is also indispensable for designing and supporting of context specific improvements against future climate changes and conservation of local cattle breeds (Marshallet al.2019). To the best of our knowledge,there is no or limited availability of functional genomic studies in African cattle. This calls for further investigation on the functional variants and key regulatory features to validate the molecular mechanisms and pathways of previously identified African cattle-specific selection signatures.

4.Conclusion

With widespread climate change and rapid protein demand,the breeding of robust animals is crucial. African cattle breeds are distributed across the continent from the highlands of the rift valley to the Afar depression.These cattle genetic resources comprise a great variety of breeds with huge potential for studies relating to genetic diversity,productivity,and role in adaptation and disease resistance. The long history of indigenous African cattle inhabit the continent develops a mosaic of environmental adaptation that is key to their survival in multiple environmental challenges. Interestingly,unlike EuropeanBostaurusand zebu cattle,AfricanBos taurusbreeds possess special genomic regions that harbor trypanotolerance and heat resistance. Therefore,uncovering the genetic footprints of recent artificial and long-term natural selections of African cattle could give insight into the mechanisms of selection in general and could,moreover,help to assign chromosomal regions related to important adaptation and agro-economic traits. The limited number of candidate genes of African cattle populations is based on European breed reference assays;this dearth to understand of the complete picture of African cattle genomic architectures may have ascertainment bias or false positive results on identified candidate genes. Therefore,assembly of the African cattle reference genome is compulsory for unbiased signitures and additional SNP discoveries. Furthermore,transcriptomic studies are indispensable to validate the molecular mechanisms and pathways of African cattlespecific selection signatures and develop custom-made breeding tools.

Acknowledgements

The authors are grateful for the financial support by the Agricultural Science and Technology Innovation Program,China (CAAS-ASTIP-2014-LIHPS-01),the China Agriculture Research System of MOF and MARA (CARS-37),the Foundation for Innovation,Groups of Basic Research in Gansu Province,China (20JR5RA580),and the Key Research and Development Programs of Science and Technology of Gansu Province,China (20YF8WA031)are duly acknowledged.

Declaration of competing interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable internaltional,national and institutional guidelines for the care and use of animals were followed.