Analysis of selection on target genes for keratinocyte exosome miRNAs in relation to human melanogenesis

Resumen

Exosomes are currently defined as a type of extracellular vesicles with a diameter of 20 to 100 nm whose origin is still not completely understood and that can carry a wide variety of molecules, such as mRNA, miRNA, cytoplasmic and membrane proteins, etc. Recently, exosomes and their cargo have been observed to play a significant role in the intercellular communication between keratinocytes and melanocytes during melanogenesis. Thus, LoCicero et al. (2015) identified a group of miRNAs, carried by keratinocytic exosomes, targeting melanocyte genes in order to regulate their expression. The main objective of this work was to identify target genes for these miRNA that were both under selection and related with melanogenesis. MiRNA target genes were predicted by computational tools such as Diana Tools and miRDB resources. DNA haplotypes for these target loci were then obtained from the 1000 Genomes Project database for both African and European populations, and were subjected to Tajima’s D test in order to detect selection on those genes. Some genes related with either pigmentation or melanoma showed to be under purifying selection. Of special interest, ERCC6, an UV-dependent gene which codes for an important nucleotide excision repair complement, showed to be under purifying selection in the African population. In addition, a region within ERCC6, which coincides with exons 11 and 12 of the gene and which comprises a binding site for c-Fos transcription factor, shows the strongest evidence of selection. This transcription factor is known to play a key role both in the regulation of melanogenesis (Tomicic et al. 2011), and in UV-induced DNA-damage repair (Torres et al. 2013).