Genome Sequence Analysis Reveals Selection Signatures in Endangered Trypanotolerant West African Muturu Cattle

Abstract

Like most West African Bos taurus , the shorthorn Muturu is under threat of replacement or crossbreeding with zebu. Their populations are now reduced to a few hundred breeding individuals and they are considered endangered. So far, the genetic variation and genetic basis of the trypanotolerant Muturu environmental adaptation have not been assessed. Here, we present genome-wide candidate positive selection signatures in Muturu following within-population iHS and between population Rsb signatures of selection analysis. We compared the results in Muturu with the ones obtained in N’Dama, a West African longhorn trypanotolerant taurine, and in two European taurine (Holstein and Jersey). The results reveal candidate signatures of selection regions in Muturu including genes linked to the innate (e.g., TRIM10, TRIM15, TRIM40 , and TRIM26 ) and the adaptive (e.g., JSP.1, BOLA-DQA2, BOLA-DQA5, BOLA-DRB3 , and BLA-DQB ) immune responses. The most significant regions are identified on BTA 23 at the bovine major histocompatibility complex (MHC) ( iHS analysis) and on BTA 12 at genes including a heat tolerance gene ( INTS6 ) ( Rsb analysis). Other candidate selected regions include genes related to growth traits/stature (e.g., GHR and GHRHR ), coat color (e.g., MITF and KIT ), feed efficiency (e.g., ZRANB3 and MAP3K5 ) and reproduction (e.g., RFX2, SRY, LAP3 , and GPX5 ). Genes under common signatures of selection regions with N’Dama, including for adaptive immunity and heat tolerance, suggest shared mechanisms of adaptation to environmental challenges for these two West African taurine cattle. Interestingly, out of the 242,910 SNPs identified within the candidate selected regions in Muturu, 917 are missense SNPs (0.4%), with an unequal distribution across 273 genes. Fifteen genes including RBBP8, NID1, TEX15, LAMA3, TRIM40 , and OR12D3 comprise 220 missense variants, each between 11 and 32. Our results, while providing insights into the candidate genes under selection in Muturu, are paving the way to the identification of genes and their polymorphisms linked to the unique tropical adaptive traits of the West Africa taurine, including trypanotolerance.

SNP Diversity in CD14 Gene Promoter Suggests Adaptation Footprints in Trypanosome Tolerant N’Dama (Bos taurus) but not in Susceptible White Fulani (Bos indicus) Cattle

“…G > A showed an incomplete mutation as there were more heterozygote alleles, this possibly indicates that the locus is still under selection pressure. As previously argued [4,6,8], this is an indication of an evolutionary adaptation event in N'Dama that is not observed in White Fulani.…”

“…Identification of single nucleotide polymorphisms (SNP) has been a beneficial strategy to unravel selection footprints within genomic regions that are potentially associated with phenotypic variation due to evolutionary adaptation [3]. Cattle breeds with differing genetic diversities have evolved due to different environmental pressures, including heat stress, infectious diseases, and harsh climate, to the end, developing unique gene variants or footprints of adaptation allowing them to cope with environmental or disease challenges [4][5][6]. It is now known that host response to pathogenic insults can result in adaptation or counter-adaptation, requiring the immune system to respond to intruding pathogens [5,7].…”

“…An in-depth understanding of the genetic diversity inherent responsible for providing tolerance or susceptibility to indigenous breeds will provide an opportunity to elucidate mechanisms of resistance to trypanosomosis and develop marker-assistant selection strategies to develop more tolerant cattle. For example, N'Dama cattle (taurine) are naturally tolerant to the pathogenic consequences of trypanosomosis, by a better capacity to control parasitemia and limit anemia development, while White Fulani cattle (indicine) on the other hand, are comparatively more susceptible to disease development [4,6]. To initiate a proper innate immune response to infection, pattern recognition receptors such as CD14, and signaling molecules such as Toll-like receptors (TLR's), are of significant importance, with the former presenting either as mCD14, expressed primarily on macrophages, dendritic cells and neutrophils, or sCD14 expressed in serum [20].…”

Signatures of Selection in CompositeVrindavaniCattle of India

“…The regions commonly detected by pairwise cross population methods (XP-EHH and F ST ) against taurine breeds on BTA4 contain the CACNA2D1 gene, which is a member of the calcium voltage-gated channel auxiliary subunit alpha-2 / delta, is previously reported to be a candidate gene associated with somatic cell score (Deng et al, 2011) and mastitis resistance (Yuan et al, 2010). Another gene on this chromosome is TFEC , reported to be a selection signature in African cattle and related with resistance to ticks and other tropical disease (Tijjani et al, 2019).…”

Investigation of ancestral alleles in the Bovinae subfamily

“…Recently, the availability of whole genome sequences (WGS) has become of increasing importance in genetic studies [2]. In cattle studies for example, WGS data of various breeds have been used for inference of demographic history, identi cation of production traits, calculation of effective population size, estimation of genetic relationships, and population structure analysis [3][4][5].…”