| Summary: | <p>Abstract</p> <p>Background</p> <p>Brain-expressed genes that were created in primate lineage represent obvious candidates to investigate molecular mechanisms that contributed to neural reorganization and emergence of new behavioural functions in <it>Homo sapiens</it>. <it>PMCHL1 </it>arose from retroposition of a pro-melanin-concentrating hormone (<it>PMCH</it>) antisense mRNA on the ancestral human chromosome 5p14 when platyrrhines and catarrhines diverged. Mutations before divergence of hylobatidae led to creation of new exons and finally <it>PMCHL1 </it>duplicated in an ancestor of hominids to generate <it>PMCHL2 </it>at the human chromosome 5q13. A complex pattern of spliced and unspliced <it>PMCHL </it>RNAs were found in human brain and testis.</p> <p>Results</p> <p>Several novel spliced <it>PMCHL </it>transcripts have been characterized in human testis and fetal brain, identifying an additional exon and novel splice sites. Sequencing of <it>PMCHL </it>genes in several non-human primates allowed to carry out phylogenetic analyses revealing that the initial retroposition event took place within an intron of the <it>brain cadherin </it>(<it>CDH12</it>) gene, soon after platyrrhine/catarrhine divergence, i.e. 30–35 Mya, and was concomitant with the insertion of an AluSg element. Sequence analysis of the spliced <it>PMCHL </it>transcripts identified only short ORFs of less than 300 bp, with low (VMCH-p8 and protein variants) or no evolutionary conservation. Western blot analyses of human and macaque tissues expressing <it>PMCHL </it>RNA failed to reveal any protein corresponding to VMCH-p8 and protein variants encoded by spliced transcripts.</p> <p>Conclusion</p> <p>Our present results improve our knowledge of the gene structure and the evolutionary history of the primate-specific chimeric <it>PMCHL </it>genes. These genes produce multiple spliced transcripts, bearing short, non-conserved and apparently non-translated ORFs that may function as mRNA-like non-coding RNAs.</p>
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