Tracking signatures of positive selection in Iranian Afshari and Moghani Sheep breeds using genomic data

Document Type : Research Paper


1 Ph.D. Candidate, Department of Animal Science, Ramin Agricultural and Natural Resources University, Iran

2 Professor, Department of Animal Science, Ramin Agricultural and Natural Resources University, Iran

3 Assistant Professor, Department of Animal Science, College of Agricultural and Natural Resources, Arak University, Iran

4 Assistant Professor, Department of Animal Science, Aburaihan campus University of Tehran, Iran

5 Research Fellow Centre for Clinical Brain Sciences, University of Edinburgh, UK


The detection of genomic regions under positive selection is one of the important topics in population genetics. The objective of the present study was to identify the genomic regions that have been under natural or artificial selection in Afshari and Moghani sheep breeds. Seventy-five samples from Afshari (N=41) and Moghani (N=34) breeds have been genotyped using the Illumina Ovine SNP50K BeadChip. Unbiased method of population differentiation index (Theta) was used to detect the positive selection signatures using Lokern R package. The results of this study revealed 16 genetic regions on chromosomes 2, 3, 4, 8, 9, 13, 15, 22 and 26 where have been under positive selection in these two Iranian sheep breeds. A majority of the genes were involved in signal transduction pathways in a wide variety of cellular and biochemical processes. In particular, selection signatures were identified spanning several genes that directly or indirectly influenced pigmentation (EDN3, BNC2), skeletal morphology and body size (ALX4, EXT2, BMP2), metabolic regulation (PPP1R3D) and immune response (IL2RB). The results of the present study and identified genomic regions suggest that the selection during the evolution and adaptation to the different environments and geographical conditions led to population differentiation in Afshari and Moghani breeds. In conclusion, finding of this study can play an important role in tracing the genomic regions associated with the distinctive traits of these two indigenous breeds.


  1. Ashrafian, H., Docherty, L., Leo, V., Towlson, C., Neilan, M., Steeples, V. & et al. (2010). A mutation in the mitochondrial fission gene Dnm1l leads to cardiomyopathy. PLoS Genetics, 6(6), e1001000.
  2. Akey, J. M., Zhang, G., Zhang, K., Jin, L. & Shriver, M. D. (2002). Interrogating a high density SNP map for signatures of natural selection. Genome Research, 12(12), 1805-1814.
  3. Alexander, M. S.,  Rozkalne, A.,  Colletta, A.,  Spinazzola, J. M. & et al. (2016). CD82 is a marker for prospective isolation of human muscle satellite cells and is linked to muscular dystrophies. Cell Stem Cell, 19(6), 800-807.
  4. Barreiro, L.B., Laval, G., Quach, H., Patin, E. & Quintana-Murci, L. (2008). Natural selection has driven population differentiation in modern humans. Nature Genetics, 40, 340-345.
  5. Bonhomme, M., Chevalet, C., Servin, B., Boitard, S., Abdallah, J. & et al. (2010). Detecting selection in population trees: the Lewontin and Krakauer test extended. Genetics, 186(1), 241-262.
  6. Browning, B. L. & Browning, S. R. (2009). A unified approach to genotype imputation and haplotype‑phase inference for large data sets of trios and unrelated individuals. American Journal of Human Genetics, 84, 210-223.
  7. Cao, P., Maximov, A. & Sudhof, T. C. (2011). Activity-dependent IGF-1 exocytosis is controlled by the Ca (2+)-sensor synaptotagmin-10. Cell, 145(2), 300-311.
  8. Cockett, N. E., Shay, T. L. & Smit, M. (2001). Analysis of the sheep genome. Physiol Genomics, 7, 69-78.
  9. Delaguillaumie, A., Harriague, J., Kohanna, S., Bismuth, G., Rubinstein, E., Seigneuret, M. & Conjeaud, H. (2004). Tetraspanin CD82 controls the association of cholesterol-dependent microdomains with the actin cytoskeleton in T lymphocytes: relevance to co-stimulation. Journal of Cell Science, 117, 5269-5282.
  10. Deng, W., Tan, Y., Wang, X., Xi, D., He, Y., Yang, S. & et al. (2009). Molecular cloning, sequence characteristics, and polymorphism analyses of the tyrosinase-related protein 2/DOPAchrome tautomerase gene of black-boned sheep (Ovis aries). Genome, 52, 1001-1011.
  11. Dong, Y., Xie, M., Jiang, Y., Xiao, N., Du, X., Zhang, W., Tosser-Klop, G., Wang, J., Yang, S., Liang, J. & et al.(2013). Sequencing and automated whole-genome optical mapping of the genome of a domestic goat (Capra hircus). Nature Biotechnology, 31, 135-141.
  12. Elferink, M. G., Megens, H. J., Vereijken, A., Hu, X., Crooijmans, R. P. M. A. & Groenen, M. A. M. (2012). Signatures of selection in the genomes of commercial and non-commercial chicken breeds. PLoS ONE, 7(2), e32720.
  13. Fariello, M. I., Servin, B., Tosser-Klopp, G., Rupp, R., Moreno, C., San Critobal, M., Boitard, S. & Consortium, I. S. G. (2014). Selection signatures in worldwide sheep populations. PLoS ONE, 9(8), e103813.
  14. GeneCards.
  15. Grazul-Bilska, A. T., Johnson, M. L., Borowicz, P. P., Minten, M., Bilski, J. J. & et al. (2011). Placental development during early pregnancy in sheep: cell proliferation, global methylation, and angiogenesis in the fetal placenta. Reproduction, 141, 529-540.
  16. Jacobs, L. C., Wollstein, A., Lao, O., Hofman, A., Klaver, C. C. & et al. (2013). Comprehensive candidate gene study highlights UGT1A and BNC2 as new genes determining continuous skin color variation in Europeans. Human Genetics, 132, 147-158.
  17. Kaplan, N. L., Hudson, R. R. & Langley, C. H. (1989). The “Hitchhiking Effect” revisited. Genetics, 123, 887-899.
  18. Kang-Decker, N., Mantchev, G. T., Juneja, S. C., McNiven, M. A. & van Deursen, J. M. A. (2001). Lack of acrosome formation in hrb-deficient mice. Science, 294(5546), 1531-1533.
  19. Kijas, J. W., Townley, D. Dalrymple, B. P., Heaton, M. P., Maddox, J. F. & et al. (2009). A genome wide survey of SNP variation reveals the genetic structure of sheep breeds. PLoS One, 4, e4668.
  20. Kijas, J. W., Lenstra, J. A., Hayes, B., Boitard, S., Porto Neto, L. R. & et al. (2012). Genome wide analysis of the world’s sheep breeds reveals high levels of historic mixture and strong recent selection. PLoS Biology, 10, e1001258.
  21. Kim, E. S., Elbeltagy, A. R., Aboul-Naga, A. M., Rischkowsky, B., Sayre, B., Mwacharo, J. M. & Rothschild, M. F. (2016). Multiple genomic signatures of selection in goats and sheep indigenous to a hot arid environment. Heredity, 116, 255-264.
  22. Khaldari, M. (2014). Sheep and goat husbandry. (5th Ed.). Jahade-daneshgahi publisher. (In Farsi).
  23. Kreitman, M. (2000). Methods to detect selection in populations with applications to the human. Annual Review of Genomics and Human Genetics, 1, 539-559.
  24. Kuijper, S., Feitsma, H., Sheth, R., Korving, J., Reijnen, M. & et al. (2005). Function and regulation of Alx4 in limb development: complex genetic interactions with Gli3 and Shh. Developmental Biology, 285, 533-544.
  25. Lim, C. H., Jeong, W., Lim, W., Kim, K., Song, G. & Bazer, F. W. (2012). Differential expression of select members of the SLC family of genes and regulation of expression by microRNAs in the chicken oviduct. Biology of Reproduction, 87(6), 1-9.
  26. Manzari, Z., Mehrabani- Yeghaneh, H., Nejati- Javaremi, A., Moradi M. H. & Gholizadeh, M. (2016). Detection of loci under positive selection in Iranian Baluchi and Zel sheep breeds. Iranian Journal of Animal Science, 47(3), 389-398.
  27. Moioli, B., Pilla, F. & Ciani, E. (2015). Signatures of selection identify loci associated with fat tail in sheep. Journal of Animal Science, 93, 4660-4669.
  28. Mokhtari, M. S., Miraei-Ashtiani, S. R., Jafaroghli, M. & Gutiérrez, J. P. (2015). Studying genetic diversity in Moghani sheep using pedigree analysis. Journal of Agricultural Science and Technology, 17, 1151-1160.
  29. Moradi, M. H., Phua, S. H., Hedayat, N., Khodaei-Motlagh, M. & Razmkabir, M. (2017). Haplotype and genetic diversity of mtDNA in indigenous Iranian sheep and an insight into the history of sheep domestication. Journal of Agricultural Science and Technology, 19(3), 591-601.
  30. Moradi, M. H., Nejati-Javaremi, A., Moradi-Shahrbabak, M., Dodds, K. G. & McEwan, J. C. (2012). Genomic scan of selective sweeps in thin and fat tail sheep breeds for identifying of candidate regions associated with fat deposition. BMC Genetics, 13, e10.
  31. Nielsen, R., Williamson, S., Kim, Y., Hubisz, M. J., Clark, A. G. & Bustament, C. (2005). Genomic scans for selective sweeps using SNP data. Genome Research, 15, 1566-1575.
  32. Norris, B. J. & Whan, V. A. (2008). A gene duplication affecting expression of the ovine ASIP gene is responsible for white and black sheep. Genome Research, 18, 1281-1293.
  33. Pourbayramian, F., Ghaderzadeh, M., Deljoo Isaloo, H. A., Biabani, P., Shams Borhan, M. B. & Barenj Foroush, P. (2012). Association study between some of biometric traits and IGF-I gene exon 1 polymorphism in Moghani sheep.  Journal of Animal Production. 14(2), 21-23. (in Farsi)
  34. Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D. & et al. (2007). PLINK: a toolset for whole-genome association and population-based linkage analysis. The American Journal of Human Genetics, 81, 559-575.
  35. Qanbari, S., Strom, T. M., Haberer, G., Weigend, S., Gheyas, A. A. & et al. (2012). A high resolution genome-wide scan for significant selective sweeps: An application to pooled sequence data in laying chickens. PLoS ONE, 7(11), e49525.
  36. Qanbari, S., Pausch, H., Jansen, S., Somel, M., Strom, T. M., Fries, R., Nielsen, R. & Simianer, H. (2014). Classic selective sweeps revealed by massive sequencing in cattle. PLOS Genetics. 10(2), e1004148.
  37. Qiu, Q., Zhang, G., Ma, T., Qian, W., Wang, J., Ye, Z. & et al. (2012). The yak genome and adaptation to life at high altitude. Nature Genetics, 44, 946-949.
  38. Qu, S., Tucker, S. C., Ehrlich, J. S., Levorse, J. M., Flaherty, L. A., et al. (1998). Mutations in mouse Aristaless-like4 cause Strong’s luxoid polydactyly. Development, 125, 2711-2721.
  39. Ravasi, T., Suzuki, H., Cannistraci, C. V., Katayama, S., Bajic, V. B. & et al. (2010). An atlas of combinatorial transcriptional regulation in mouse and man. Cell, 140,744-752.
  40. Sponenberg, D. P. (1997). Genetics of colour and hair texture. In: Piper LR, Ruvinsky A (eds) The Genetics of Sheep. CAB International: Wallingford, UK, pp. 51-85.
  41. Stella, A., Ajmone-Marsan, P., Lazzari, B. & Boettcher, P. (2010). Identification of selection signatures in cattle breeds selected for dairy production. Genetics, 185, 1451-1461.
  42. Stickens, D., Zak, B. M., Rougier, N., Esko, J. D. & Werb, Z. (2005). Mice deficient in Ext2 lack heparan sulfate and develop exostoses. Development, 132, 5055-5068.
  43. Teo, Y. Y., Fry, A. E., Clark, T. G., Tai, E. S. & Seielstad, M. (2007). On the usage of HWE for identifying genotyping errors. Annals of Human Genetics, 71, 701-703.
  44. The R project for statistical computing: Free software environment for statistical computing and graphics. http://
  45. UniProtKB Gene.
  46. Wang, H., Zhang, L., Cao, J., Wu, M., Ma, X., Liu, Z. & et al. (2015). Genome-wide specific selection in three domestic sheep breeds. PLoS ONE, 10(6), e0128688.
  47. Wei, C. H., Wang, H. H., Liu, G., Wu, M. M., Cao, J. X. V., Liu, Z. & et al. (2015). Genome-wide analysis reveals population structure and selection in Chinese indigenous sheep breeds. BMC Genomics, 16, 194.
  48. Weir, B. S. & Cockerham, C. C. (1984). Estimating F-Statistics for the analysis of population structure. Evolution, 38(6), 1358-1370.
  49. Xu, L., Bickhart, D. M., Cole, J. B., Schroeder, S. G., Song, J., Tassell, C. P. & et al. (2015). Genomic signatures reveal new evidences for selection of important traits in domestic cattle. Molecular Biology and Evolution, 32, 711-725.