Comparative genomics of human stem cell factor (SCF)

Abstract

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.

Keywords: Chimpanzee; Comparative genomics; Neanderthal; Stem cell factor.

Figure 1

Alternative splicing of SCF. Alternative splicing of the sixth exon of SCF mRNA produces two membrane bound forms, SCF²⁴⁸ and SCF²²⁰. SCF248 is cleaved by proteases in the domain encoded by exon 6 ( ) to produce a soluble 165 amino acid protein (SCF165 or sSCF). SCF220 or mSCF remains membrane-bound as it lacks the proteolytic cleavage site encoded by exon 6, but it may also be shed in the region encoded by exon 7 to produce a soluble form [10].

Figure 2

Signal transduction pathways of the c-Kit receptor. Homodimerized SCF binds itself to c-Kit, thus inducing c-Kit homodimerization and autophosphorylation, and activation of different signalling pathways. Activation of the PI3-kinase, Src and the small G protein Ras, in turn, induce the activation of different MAP-kinase pathways: ERK (extracellular-regulated kinase), p38 and JNK (Jun-N-terminal kinase). PI3-kinase also activates Akt/PKB. The Janus kinase (JAK) is associated with phosphorylated c-Kit, activatingthe transcription factor STAT (Signal Transducers and Activators of Transcription), SOS (son of sevenless); Grb-2: growth factor receptor-bound protein-2; MEK: MAP ERK kinase [10].

Figure 3

Phylogenic analysis of SCF cDNA sequences. BAST analysis and phylogenetic tree of cDNA sequences of SCF using NCBI BLAST tree view, Neighbor joining clustering method and Max Seq Difference 0.75

Figure 4

BLAST analysis of the cDNA sequence of human SCF using MEGA6 software

Figure 5

Phylogenetic tree of primates proposed by McKenna and Bell in 1997 [28].

Figure 6

Conservation of SCF gene. The single copy and conservation of SCF gene across Neanderthal genomes using Neanderthal genomes database (https://bioinf.eva.mpg.de/jbrowse/). Blue and red dots refer to homozygous and heterozygous variants, respectively