ABSTRACT

Objective: The interleukin-4 receptor gene (IL-4R) is a critical component of immune signaling pathways and plays an essential role in regulating immune responses and reproductive functions in mammals. The present study aimed to investigate the genetic diversity of the IL-4R gene sequence and to compare nucleotide variation, substitution patterns, selective pressures, and phylogenetic relationships between European cattle (Bos taurus) and Indian cattle (Bos indicus).

Method: For this purpose, 26 nucleotide sequences related to different breeds of both European and Indian species were extracted from the NCBI and Ensemble databases and aligned. Alignment of gene sequences was performed using the CLUSTAL-W algorithm in MEGA software version11. Then, the number and types of mutations and the amount of polymorphism, nucleotide diversity, the number of positions where similar or non-similar substitutions occurred, the percentage of gene divergence, the percentage of transitional and transversional substitutions and gene conversion were calculated using MEGA11 and Dnaspv5 software. The percentage of nucleotide transition and transversion substitutions was calculated using the composite maximum likelihood method. Haplotype diversity was calculated based on the maximum likelihood method and genetic distance was calculated based on the Tamura-Nei model and finally the phylogenetic tree was drawn using the Neighbor-joining (NJ) method. To assess selective pressure acting on the IL-4R gene, the ratio of nonsynonymous to synonymous substitutions (dN/dS) was estimated.

Results: Nucleotide diversity was estimated to be 0.33 in European cattle and 0.214 in Indian cattle, demonstrating a higher level of genetic variability in Bos taurus compared to Bos indicus. In all analyzed populations, the frequency of transitional substitutions was higher than that of transversional substitutions. The dN/dS ratio was calculated as 0.9 for European cattle, indicating that purifying selection has predominantly acted on the IL-4R gene during its evolution in this group. In contrast, the dN/dS ratio in Indian cattle was estimated to be 1.11, suggesting evidence of positive selection acting on this gene locus. Phylogenetic analysis revealed distinct evolutionary patterns of the IL-4R gene among the studied populations. Although both cattle groups share a common ancestor, European cattle exhibit greater evolutionary divergence and appear to have a longer evolutionary history for this gene compared to Indian cattle.

Conclusions: The findings of the present study indicated different evolutionary patterns in European and Indian cattle. The dominance of pure selection in European cattle and the presence of evidence of positive selection in Indian cattle indicate that the IL-4R gene has been under different selective pressures during the evolutionary process. Therefore, in addition to a better understanding of the molecular evolution and genetic diversity of immune genes in cattle, the aforementioned results can be used in future breeding strategies in cattle, especially in the field of immune function and disease resistance.