Evolutionary Origin and Genomic Organization of Micro-RNA Genes in Immunoglobulin Lambda Variable Region Gene Family

The genomic organizations and functions of many miRNA genes have been described in recent years, but the origin and evolution of miRNAs in the exons of protein-coding genes are not well understood. The overlap of miR-650 genes with the protein-coding region of immunoglobulin lambda variable (IGVL) region genes has given a unique opportunity to witness a birth of miRNA gene. Both sequence comparisons and structure predictions indicate that the miR-650 genes are present in multiple copies and overlap in the same transcription orientation with the leader exon of primate IGVL genes of a specific phylogenetic clan (clan II). By reconstructing the phylogeny of the clan II IGVL genes, the stages in which the mutations accumulated in the leader exon and gave rise to a stable hairpin structure of miR-650 could be documented. The copy number variation of miR-650 genes among different species is the result of the duplication or deletion of the IGVL genes. To my knowledge, this is the first report of a genomic association between miRNA and the protein-coding genes of a multigene family. Analysis of the upstream region of the leader exon suggests that the IGVL and the mir-650 genes use the same promoter region for their transcription. However, in contrast to the general expectation about the expression of miRNAs that overlap with other genes in the same transcriptional orientation, this analysis provides evidence that the miR-650 gene is apparently transcribed independently of the IGVL gene with which it overlaps because they are expressed in different cell types.