Comparative genomics of human stem cell factor (SCF)

Document Type: Original article


Genetics Division, Department of Biology, Faculty of Science, University of Isfahan, Isfahan, Iran


Stem cell factor (SCF) is a critical protein with key roles in the cell such as hematopoiesis, gametogenesis and melanogenesis. In the present study a comparative analysis on nucleotide sequences of SCF was performed in Humanoids using bioinformatics tools including NCBI-BLAST, MEGA6, and JBrowse. Our analysis of nucleotide sequences to find closely evolved organisms with high similarity by NCBI-BLAST tools and MEGA6 showed that human and Chimpanzee (Pan troglodytes) were placed into the same cluster. By using JBrowse, we found that SCF in Neanderthal had a single copy number similar to modern human and partly conserved nucleotide sequences. Together, the results approved the gene flow and genetics similarity of SCF among human and P. troglodytes. This may suggest that during evolution, SCF gene transferred partly intact either on the basis of sequence or function from the same ancestors to P. troglodytes, the ancient human like Neanderthal, and then to the modern human.


1. Ali S, Ali S. Role of c-kit/SCF in cause and treatment of gastrointestinal stromal tumors (GIST). Gene 2007;401:38-45.

2. Hutt KJ, McLaughlin EA, Holland MK. Kit ligand and c-Kit have diverse roles during mammalian oogenesis and folliculogenesis. Mol Hum Reprod 2006;12:61-69.

3. Anderson DM, Anderson DM, Williams DE, Tushinski R, Gimpel S, Eisenman J, Cannizzaro LA, Aronson M, Croce CM, Huebner K, Cosman D, Lyman SD Alternate splicing of mRNAs encoding human mast cell growth factor and localization of the gene to chromosome 12q22-q24. Cell Growth Differ 1991;2:373-378.

4. Linnekin D. Early signaling pathways activated by c-Kit in hematopoietic cells. Int J Biochem Cell Biol 1999;31:1053-1074.

5. Zhang Z, Zhang R, Joachimiak A, Schlessinger J, Kong XP. Crystal structure of human stem cell factor: implication for stem cell factor receptor dimerization and activation. Proc Natl Acad Sci USA 2000;97:7732-7737.

6. Martin FH, Martin FH, Suggs SV, Langley KE, Lu HS, Ting J, Okino KH, Morris CF, McNiece IK, Jacobsen FW, Mendlaz EA, Birkett NC, Smith KA, Johnson MJ, Parker VP, Flores JC, Patel AC, Fisher EF, Erjavec HO, Herrera CJ, Wypych J, Sachdev RK, Pope JA, Leslie I, Wen D, Lin CH, Cupples RL, Zsebo KMPrimary structure and functional expression of rat and human stem cell factor DNAs. Cell 1990;63:203-211.

7. Williams DE, de Vries P, Namen AE, Widmer MB, Lyman SD. The Steel factor. Dev Biol 1992;151:2368-2376.

8. Pandiella A, Bosenberg MW, Huang EJ, Besmer P, Massague J. Cleavage of membrane-anchored growth factors involves distinct protease activities regulated through common mechanisms. J Biol Chem 1992;267:24028-24033.

9. Huang EJ, Nocka KH, Buck J, Besmer P. Differential expression and processing of two cell-associated forms of the kit ligand: KL-1 and KL-2. Mol Biol Cell 1992;3: 349-362.

10. Reber L, Da Silva CA, Frossard N. Stem cell factor and its receptor c-Kit as targets for inflammatory diseases. Eur J Pharmacol 2006;533:327-340.

11. Langley KE, Langley K, Mendiaz EA, Liu NL, Narhi LO, Zeni L, Parseghian CM, Clogston CL, Leslie IJ, Pope J, Zsebo KM, Boone TC Proprieties of variant forms of human stem cell factor recombinantly expressed in Escherichia coli. Arch Biochem Biophys 1994;311:55-61.

12. Lev S, Givol D, Yarden Y. Interkinase domain of kit contains the binding site for phosphatidylinositol 3¢ kinase. Proc Natl Acad Sci USA 1992;89:678-682.

13. Deshpande S, Agosti V, Manova K, Moore MA, Hardy MP, Besmer P. Kit ligand cytoplasmic domain is essential for basolateral sorting in vivo and has roles in spermatogenesis and hematopoiesis. Dev Biol 2010;337:199-210.

14. Kissel H, Timokhina I, Hardy MP, Rothschild G, Tajima Y, Soares V, Angeles M, Whitlow SR, Manova K, Besmer P. Point mutation in kit receptor tyrosine kinase reveals essential roles for kit signaling in spermatogenesis and oogenesis without affecting other kit responses. EMBO J 2000;19:1312-1326.

15. Manova K, Nocka K, Besmer P, Bachvarova RF. Gonadal expression of c-kit encoded at the W locus of the mouse. Development 1990;110:1057-1069.

16. Vincent S, Segretain D, Nishikawa S, Nishikawa SI, Sage J, Cuzin F, Rassoulzadegan M. Stage-specific expression of the Kit receptor and its ligand (KL) during male gametogenesis in the mouse: a Kit-KL interaction critical for meiosis. Development 1998;125:4585-4593.

17. Munugalavadla V, Kapur R. Role of c-Kit and erythropoietin receptor in erythropoiesis. Crit Rev Oncol Hematol 2005;54:63-75.

18. Javadirad SM, Vallian S. Phylogenic analysis of cellular life forms using U5 Snrnp components. J Appl Bioinform Comput Biol 2014;3:1-4.

19. Diogo R, Wood BA, Aziz MA, Burrows A. On the origin, homologies and evolution of primate facial muscles, with a particular focus on hominoids and a suggested unifying nomenclature for the facial muscles of the Mammalia. J Anat 2009;215: 300-319.

20. Goodman M, Porter CA, Czelusniak J, Page SL, Schneider H, Shoshani J, Gunnell G, Groves CP. Toward a phylogenetic classification of Primates based on DNA evidence complemented by fossil evidence. Mol Phylogenet Evol 1998;9:585-598.

21. Nishihara H, Maruyama S, Okada N. Retroposon analysis and recent geological data suggest near-simultaneous divergence of the three superorders of mammals. Proc Natl Acad Sci USA 2009;106:5235-5240.

22. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: Molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 2013;30:2725-2729.

23. Zhang Z, Schwartz S, Wagner L, Miller W. A greedy algorithm for aligning DNA sequences. J Comput Biol 2000;7:203-214.

24. Saitou N, Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 1987;4:406-425.

25. Desper R, Gascuel O. Theoretical foundation of the balanced minimum evolution method of phylogenetic inference and its relationship to weighted least-squares tree fitting. Mol Biol Evol 2004;21:587-598.

26. Janecka JE, Miller W, Pringle TH, Wiens F, Zitzmann A, Helgen K M, Springer MS, Murphy WJ. Molecular and Genomic Data Identify the Closest Living Relative of Primates. Science 2007;318:792-794.

27. Thorington R W, Anderson S. Primates. In: Anderson S, Jones JK, Orders and Families of Recent Mammals of the World. Wiley, New York, 1984; pp. 187-217.

28. McKenna MC, Bell SK. Classification of Mammals: Above the species level, New York, Columbia University Press. 1997; p. 631. ISBN 0-231-11013-8.

29. Goodman M, Tagle DA, Fitch DH, Bailey W, Czelusniak J, Koop BF, Benson P, Slightom JL. Primate evolution at the DNA level and a classification of hominoids. J Mol Evol 1990;30:260-266.

30. Jauch A, Wienberg J, Stanyon R, Arnold N, Tofanelli S, Ishida T, Cremer T. Reconstruction of genomic rearrangements in great apes and gibbons by chromosome painting. Proc Natl Acad Sci USA 1992;89:8611-8615.

31. Hartwig W. Chapter 3: Primate evolution. In: Campbell CJ, Fuentes A, MacKinnon KC, Bearder SK, Stumpf RM (ed) Primates in Perspective, 2nd ed. Oxford University Press. 2011; pp. 19-31. ISBN 978-0-19-539043-8.

32. Cartmill M. Primate Classification and Diversity. In: Platt M, Ghazanfar, A (ed) Primate Neuroethology. Oxford University Press. 2010; pp. 10-30. ISBN 978-0-19-532659-8.

33. Strier K. Primate Behavioral Ecology, 3rd edn, 2007; pp. 50-53. ISBN 0-205-44432-6.

34. Mishler, Brent D. Species are not Uniquely Real Biological Entities, In: Ayala FJ, Arp R, Contemporary Debates in Philosophy of Biology, 2009; pp. 110-122, ISBN 978-1-4443-1492-2, p. 114.

35. Springer MS, Meredith RW, Gatesy J, Emerling CA, Park J, Rabosky DL, Stadler T, Steiner C, Ryder OA, Janecka JE, Fisher CA, Murphy WJ. Macroevolutionary dynamics and historical biogeography of primate diversification inferred from a species supermatrix. PLoS One 2012;7:e49521.

36. Rogers J, Gibbs RA. Comparative primate genomics: emerging patterns of genome content and dynamics. Nat Rev Genet 2014;15:347-359.

37. Marques-Bonet T, Marques-Bonet T, Kidd JM, Ventura M, Graves TA, Cheng Z, Hillier LW, Jiang Z, Baker C, Malfavon-Borja R, Fulton LA, Alkan C, Aksay G, Girirajan S, Siswara P, Chen L, Cardone MF, Navarro A, Mardis ER, Wilson RK, Eichler EE A burst of segmental duplications in the genome of the African great ape ancestor. Nature 2009;457:877-881.

38. Fortna A, et al. Lineage-specific gene duplication and loss in human and great ape evolution. PLoS Biol 2004;2:e207.

39. Skinner ME1, Uzilov AV, Stein LD, Mungall CJ, Holmes IH. JBrowse: a next-generation genome browser. Genome Res 2009;19:1630-1638.

40. Pääbo S. The diverse origins of the human gene pool. Nat Rev Genet 2015;16:313-314.