BoLA-DRB3 gene haplotypes show divergence in native Sudanese cattle from Taurine and Zebu breeds

Autochthonous Sudanese cattle breeds, namely Baggara for beef and Butana and Kenana for dairy, are characterized by their adaptive characteristics and high performance in hot and dry agro-ecosystems, are used largely by nomadic and semi-nomadic pastoralists. Here we analyzed the diversity and genetic structure of the BoLA-DRB3 gene, a genetic locus linked to the immune response, for the indigenous cattle of Sudan and in the context of the global cattle repository. Blood samples (n=225) were taken from three indigenous breeds (Baggara; n=113, Butana; n= 60 and Kenana; n=52) distributed across six regions of Sudan. Nucleotide sequences were genotyped using the sequence-based typing method. Sequence electropherograms were analyzed using the Assign SBT software. We describe 53 alleles, including seven new, novel alleles. In the Baggara breed the number of alleles was 46 (40 previously reported and six new ones), 33 in the Kenana breed (28 previously reported and five new ones), and 33 in the Butana breed (28 previously reported and five new ones). Venn analysis of Sudanese breeds with Southeast Asian, European and American cattle showed 115 alleles of which 14 were unique to Sudanese breeds. Three of the alleles exhibited gene frequency of > 0.5%, representing 26% of the 53 alleles detected in the native Sudanese cattle. Observed versus expected heterozygosity was higher than 0.93 in all three breeds analyzed and equilibrium status revealed by Hardy-Weinberg Equilibrium suggests pure genetic drift. Gene frequency distributions of Baggara cattle showed an even distribution (P = 0.016), consistent with the theoretical proportion expected under balancing selection pressure as opposed to positive or neutral selection. In contrast, Butana and Kenana cattle (P = 0.225 and P = 0.138, respectively) were more congruent with neutral selection, similar to the results obtained for most of the cattle breeds analyzed so far. Sudanese cattle breeds were located within a narrow cloud in an intermediate position between the Zebu and Taurine breeds and close to other Southeast Asian breeds, in accordance with the composite origin of these native breeds, which is also reinforced by the presence of African and Zebu unique BoLA-DRB3 alleles within these breeds. The results of the Principal Component Analysis were in agreement with the overall clustering pattern observed on the NJ and/or UPGMA trees. These results contribute to our understanding of the genetic diversity and distribution pattern of BoLA-DRB3 gene alleles in Sudanese cattle breeds and provide insight into their uniqueness in their ability to survive arrays of tropical diseases and reproduce well in Sudan’s harsh environment.Author summaryAfrican cattle survive and adapt to a variety of diseases via acquired immunity capable of presenting antigens through the function of the major histocompatibility complex (MHC) or bovine leukocyte antigen (BoLA) in cattle. The aim of this study was to investigate how the immune system is structured and to what extent three economically important breeds in Sudan differ from exotic cattle. Here, we use the sequence-based typing approach to analyze BoLA-DRB3’s genetic diversity linked to immunity against complex diseases that infect cattle. By examining 225 indigenous cattle belonging to three breeds in Sudan, we demonstrate that these cattle are unique from all known cattle by identifying seven new alleles; BoLA-DRB3*004:02Sp, BoLA-DRB3*011:02Sp, BoLA-DRB3*018:01Sp, BoLA-DRB3*021:01sp, BoLA-DRB3*024:18Sp, BoLA-DRB3*027:05sp, and BoLA-DRB3*032:01sp. When analyzing frequency of the protein pockets implicated in the antigen-binding function of the MHC complex by PCA we found that pockets 4 and 9 are the ones that best differentiate these native breeds from the rest. This may be attributed to high disease tolerance/susceptibility to tropical infections, such as those carried by ticks and intestinal parasites. Further studies are needed on these newly identified variants and their association with specific common disease(s). This finding is especially important for disease resistance/susceptibility association to help advise on candidate animals in selection schemes.

Δ-dN/dS: A New Criteria to Distinguish among Different Selection Modes in Gene Evolution

One of the most widely-used measures for protein evolution is the ratio of nonsynonymous distance (dN) to synonymous distance (dS). Under the assumption that synonymous substitutions in the coding region are selectively neutral, the dN/dS ratio can be used to test the adaptive evolution if dN/dS>1 statistically significantly. However, due to selective constraints imposed on amino acid sites, most encoding genes demonstrate dN/dS<1. As a result, dN/dS of a gene is less than 1, even some sites may have experienced positive selections. In this paper, we develop a new criterion, called Δ-dN/dS, for positive selection testing by introducing an index H, which is a relative measure of rate variation among sites. Under the context of strong purifying selection at some amino acid sites, our model predicts dN/dS=1-H for the neutral evolution, dN/dS<1-H for the nearly-neutral selection, and dN/dS>1-H for the adaptive evolution. The potential of this new method for resolving the neutral-adaptive debates has been illustrated by case studies. For over 4000 vertebrate genes, virtually all of them showed dN/dS<1-H, indicating the dominant role of the nearly-neutral selection in molecular evolution. Moreover, we calculated the dN/dS ratio for cancer somatic mutations of a human gene, specifically denoted by CN/CS. For over 4000 human genes in cancer genomics, about 55% of genes showed 1-H<CN/CS<1, about 45% of genes showed CN/CS<1, whereas less than 1% of genes showed CN/CS<1-H. Together our analysis suggested driver mutations, i.e., those initiate and facilitate carcinogenesis, confer a selective advantage on cancer cells, leading to CN/CS>1 (strong positive selection) or 1-H<CN/CS<1 (weak positive selection, combined with strong purifying selection), whereas nearly neutral selection due to reduced effective clonal size is highly unlikely in cancer evolution.

Diversidad haplotípica del exón XII del gen dopamina β-hidroxilasa en tres razas bovinas

Polymorphisms in the dopamine β-hydroxylase gene (DBH) have been associated with temperament in cattle. In 16 animals of Colombian creole breed Blanco Orejinegro (BON), 20 Brahman (BRA) and 16 fighting bulls (GLI), polymorphisms of exon XII of the DBH gene were evaluated by sequencing. 13 haplotypes were found, 6 in BON, 9 and 2 in BRA and GLI respectively. Haplotype H2 was the most frequent in the whole population (0,615) and it was found in all breeds. Haplotypes H6 and H9 were shared between BON-BRA and BRA-GLI, respectively. The greatest value of genetic(DG: 0.915 ± 0.04) and nucleotide (DN: 0.011 ± 0.006) diversity, was found in BRA, followed by BON (DG: 0.700 ± 0.12; DN: 0.008 ± 0.004) and GLI (DG: 0.350 ± 0.14;DN: 0.0011 ± 0.001). The D-Tajima test was greater than zero, but not significant (P> 0.05) in BON and BRA, GLI presented a value of −1.92 (P < 0.05). The analysis of molecular variance showed a variation between the breeds of 23.9% and a poblacional structure (FST) of 0.23 (P < 0.001). The highest values of the coancestry coefficient were presented between GLI and BRA (0.52) and between GLI and BON (0.22). It is concluded that the GLI race has low diversity in the DBH gene compared to BON and BRA, that there are effects of neutral selection in BON and BRA breeds, whereas, in the GLI and not in favor of temperament.

Interpreting Selectivity Indices Calculated from Field Data or Conditions of Prey Replacement

Indices of prey selection are compared empirically to clarify the kind of information each can provide and when the indices can be used appropriately. Emphasis is given to Chesson's alpha (α) and Strauss' Linear index (Li) because they are commonly used and represent two mathematically dissimilar approaches to measuring selection. Neutral selection for α and Li is not equivalent. For Li, neutral selection for a prey type occurs when selectivity equals the weighted (by relative abundance) average selectivity for all other prey types. For α, neutral selection equals the unweighted average for all prey types, which is equivalent to 1 divided by the number of prey types. Li and α respond differently to rare prey types. This is especially evident in field samples having large differences in relative prey abundances. Li values decrease as abundance of a prey type decreases in the environment, in contrast, α values often increase greatly as the proportional abundance of a prey type in the environment decreases. Consequently, α values, but not Li values, are often strongly influenced by the values for very rare prey, α values are sensitive to changes in the number of prey types, but not to changes in prey proportion. When the number of prey types is constant, α may be the most meaningful indicator of prey type preference. In contrast, Li values are sensitive to changes in prey proportions in the environment. When prey proportions are constant among experiments, Li is appropriate for measuring changes in the impact of a predator on a prey type and changes in selectivity relative to the average prey item. If number of prey types and prey proportions vary among experiments, Vanderploeg and Scavia's W or E* may be most appropriate.