Genetic diversity analysis of the Interleukin-4 receptor gene (IL-4R) sequence in Bos taurus and Bos indicus cattle

Document Type : Research Paper

Authors

1 Department of Animal Science, Faculty of Agriculture, University of Zabol, Zabol, Iran. E-mail: arghavan.bastam@uoz.ac.ir

2 Corresponding Author, Department of Animal Science, Faculty of Agriculture, University of Zabol, Zabol, Iran. E-mail: dashab@uoz.ac.ir

3 Department of Animal Science, Faculty of Agriculture, University of Zabol, Zabol, Iran. E-mail: h.bazzi@uoz.ac.ir

Abstract
Objective: Interleukin-4 receptor gene (IL-4R) is an important molecule in immune signaling pathways that control immune responses and reproductive functions in mammals. The objective of this study was to explore the IL-4R gene sequence diversity and to compare nucleotide variation, substitution patterns, selective pressures, and phylogenetic relationships between European cattle (Bos taurus) and Indian cattle (Bos indicus).
Method: In this regard, we retrieved 26 nucleotide sequences from the NCBI and Ensemble databases related to various breeds of both European and Indian species and aligned them using the CLUSTAL-W algorithm in MEGA, and subsequently the number and types of mutations and the amount of polymorphism, nucleotide diversity, the number of similar and non-similar substitutions, the percentage nucleotide transition and transversion substitutions was 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: The nucleotide diversity was estimated to be 0.33 in European cattle and 0.214 in Indian cattle, which suggests a higher level of genetic variability of Bos taurus compared to Bos indicus. The frequency of transitional substitutions was higher than the frequency of trans versional substitutions in all populations examined. The dN/dS ratio was 0.9 in European cattle, while that of Indian cattle was 1.11, suggesting that the IL-4R gene is under positive selection in Indian cattle. The results of phylogenetic analysis of the IL-4R gene showed that the gene in both groups of cattle had different evolutionary patterns, although they share a common ancestor, and that European cattle had more evolutionary divergence and likely have had a longer evolutionary time for this gene compared to Indian cattle.
Conclusions: The results of this study revealed distinct evolutionary patterns in European and Indian cattle. The results also suggest that the IL-4R gene has experienced distinct selective pressures in the evolutionary process between European and Indian cattle, where pure selection dominates in European cattle and there is evidence of positive selection in Indian cattle. Thus, besides furthering the molecular evolution and genetic diversity of immune genes in cattle, the above results can be applied to the breeding strategies of cattle in the future, especially in the area of immune function and disease resistance.

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Reference
Achilli, A., Bonfiglio, S., Olivieri, A., Malusà, A., Pala, M., Kashani, B.H., Perego, U.A., Ajmone-Marsan, P., Liotta, L., Semino, O., & Bandelt, H.J. (2009). The multifaceted origin of taurine cattle reflected by the mitochondrial genome. PloS one, 4(6), e5753. e5753. doi: 10.1371/journal.pone.0005753.
Buitkamp, J., Schwaiger, F. W., Solinas-Toldo, S., Fries, R., & Epplen, J. T. (1995). The bovine interleukin-4 gene: genomic organization, localization and evolution. Mamm. Genome, 6(5), 350-356. doi: 10.1007/BF00364799.
Coffman, R. L., Lebman, D. A., & Rothman, P. (1993). Mechanism and regulation of immunoglobulin isotype switching. Advances in Immunology, 54, 229-270. doi: 10.1016/s0065-2776(08)60536-2.
Decker, J.E., McKay, S.D., Rolf, M.M., Kim, J., Molina Alcalá, A., Sonstegard, T.S., Hanotte, O., Götherström, A., Seabury, C.M., Praharani, L., & Babar, M.E. (2014). Worldwide patterns of ancestry, divergence, and admixture in domesticated cattle. PLoS genetics, 10(3), e1004254. e1004254. doi: 10.1371/journal.pgen.1004254.
Deichmann, K., Bardutzky, J., Forster, J., Heinzmann, A., & Kuehr, J. (1997). Common polymorphisms in the coding part of the IL4 receptor gene. Biochemical and Biophysical Research Communications, 231, 696-697. doi: 10.1006/bbrc.1997.6115.
Dutta, R., Singh, V. K., Kumar, A., Singh, R., Singh, P., Chaurasia, A. K., & Singh, S. P. (2022). Genomic diversity and signatures of selection in Indian indigenous cattle breeds. Scientific Reports, 12(1), 13485. doi: 10.1139/gen-2022-0106.
Faaz, R. A., & Abdullah, F. A. (2022). Expressions of IL4, IL10, and IFNγ cytokine genes during bacterial mastitis. Journal of Advanced Veterinary and Animal Research, 9(1), 42. doi: 10.5455/javar.2022.i567.
Gilioli da Costa Nunes, G., Cezar Aquino de Moraes, F., de Cássia Calderaro Coelho, R., Rodrigues Fernandes, M., Emanuel Batista dos Santos, S., & Pereira Carneiro dos Santos, N. (2025). Single-nucleotide polymorphisms related to glioblastoma risk and worldwide epidemiology: A systematic review and meta-analysis. Journal of Personalized Medicine, 15(9), 401. doi: 10.3390/jpm15090401.
Iso-Touru, T., Kesti, T., Purmonen, K., Karkkainen, L., & Rikkilä, K. (2021). Whole-genome variation in global cattle breeds. Genetics Selection Evolution, 53(1), 32. doi: 10.1186/1471-2164-12-557.
Karimi, V., Hedayat Evrigh, N., Seyed Sharifi, R., & Nikbin, S. (2017). Investigation of genetic structure of Khalkhali goat using mitochondrial genome. Novin Genetic Journal, 12(2), 217-227.
Kohanbash, G., McKaveney, K., Sakaki, M., Ueda, R., Mintz, A. H., Amankulor, N., Fujita, M., Ohlfest, J. R., & Okada, H. (2013). GM-CSF promotes the immunosuppressive activity of glioma-infiltrating myeloid cells through interleukin-4 receptor-α. Cancer Research, 73, 6413-6423. doi: 10.1158/0008-5472.CAN-12-4124.
Korber, B. (2000). HIV signature and sequence variation analysis. In A. G. Rodrigo & G. H. Learn (Eds.), Computational analysis of HIV molecular sequences (pp. 55–72). Kluwer Academic Publishers.
Lopes, F. B., Silva, L. A., Lima, L. A. & Silva, M. A. (2023). Advances in genomic selection for economically important traits in cattle. Frontiers in Genetics, 14, 1173468. doi: 10.3390/ani15131960.
MacHugh, D. E., Shriver, M. D., Loftus, R. T., Cunningham, P., & Bradley, D. G. (1997). Microsatellite DNA variation and the evolution, domestication and phylogeography of taurine and zebu cattle (Bos taurus and Bos indicus). Genetics, 146(3), 1071-1086. doi: 10.1093/genetics/146.3.1071.
Magee, D. A., MacHugh, D. E., & Edwards, C. J. (2014). Interrogation of modern and ancient genomes reveals the complex domestic history of cattle. Animal Frontiers, 4(3), 7-22. doi.org/10.2527/af.2014-0017.
Nayeri, S., Schenkel, F., Fleming, A., Kroezen, V., Sargolzaei, M., Baes, C., Cánovas, A., Squires, J., & Miglior, F. (2019). Genome-wide association analysis for β-hydroxybutyrate concentration in milk in Holstein dairy cattle. BMC Genetics, 20(1), 58. doi: 10.1186/s12863-019-0761-9.
Nei, M., & Kumar, S. (2000). Molecular evolution and phylogenetics. Oxford University Press.
Norseeda, W., Liu, G., Teltathum, T., Supakankul, P., Sringarm, K., Naraballobh, W., Khamlor, T., Chomdej, S., Nganvongpanit, K., Krutmuang, P., & Mekchay, S. (2021). Association of IL-4 and IL-4R polymorphisms with litter size traits in pigs. Animals, 11(4), 1154. doi: 10.3390/ani11041154.
Ober, C., Cox, N. J., Abney, M., Di Rienzo, A., Lander, E. S., Changyaleket, B., Gidley, H., Kurtz, B., Lee, J., Nance, M., Pettersson, A., Prescott, J., Richardson, A., Schlenker, E., Summerhill, E., Willadsen, S., & Parry, R. (1998). Genome-wide search for asthma susceptibility loci in a founder population. Human Molecular Genetics, 7, 1393-1398. doi.org/10.1093/hmg/7.9.1393.
Rosse, I.C., Assis, J.G., Oliveira, F.S., Leite, L.R., Araujo, F., Zerlotini, A., Volpini, A., Dominitini, A.J., Lopes, B.C., Arbex, W.A., & Machado, M.A. (2017). Whole genome sequencing of Guzerá cattle reveals genetic variants in candidate genes for production, disease resistance, and heat tolerance. Mammalian genome, 28(1), 66-80.
Shackelford, S. D., Wheeler, T. L., & Koohmaraie, M. (1995). Relationship between shear force and trained sensory panel tenderness ratings of 10 major muscles from Bos indicus and Bos taurus cattle. Journal of Animal Science, 73(11), 3333-3340. doi: 10.2527/1995.73113333x.
Tamura, K., Stecher, G., & Kumar, S. (2021). MEGA11: Molecular evolutionary genetics analysis version 11. Molecular Biology and Evolution, 38(7), 3022-3027. https://doi.org/10.1093/molbev/msab120.
Verdugo, M.P., Mullin, V.E., Scheu, A., Mattiangeli, V., Daly, K.G., Maisano Delser, P., Hare, A.J., Burger, J., Collins, M.J., Kehati, R. and Hesse, P. (2019). Ancient cattle genomics, origins, and rapid turnover in the Fertile Crescent. Science, 365(6449), 173-176. doi: 10.1126/science. aav1002.
Vigne, J.-D. (2011). The origins of animal domestication and husbandry: A major change in the history of humanity and the biosphere. Comptes Rendus Biologies, 334(3), 171-181. https://doi.org/10.1016/j.crvi.2010.12.009.
Yin, T., Tsang, M. L., & Yang, Y.-C. (1994). JAK1 kinase forms complexes with the interleukin-4 receptor and insulin receptor substrate-1–like protein and is activated by interleukin-4 and interleukin-9 in T lymphocytes. Journal of Biological Chemistry, 269, 26614-26617. https://www.jbc.org/article/S0021-9258(18)47061-5/pdf
Zhang, F., Wang, Y., Mukiibi, R., Chen, L., Vinsky, M., Plastow, G., Basarab, J., Stothard, P., & Li, C. (2020). Genetic architecture of quantitative traits in beef cattle revealed by genome wide association studies of imputed whole genome sequence variants: I: feed efficiency and component traits. BMC Genomics, 21(1): 36. doi: 10.1186/s12864-019-6362-1.