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Open Access Research article

Primate-specific spliced PMCHL RNAs are non-protein coding in human and macaque tissues

Sandra Schmieder1, Fleur Darré-Toulemonde14, Marie-Jeanne Arguel12, Audrey Delerue-Audegond12, Richard Christen3 and Jean-Louis Nahon12*

Author Affiliations

1 Université de Nice-Sophia Antipolis, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, 660 route des lucioles, 06560 Valbonne, France

2 Biothèque Primates/Primatech, Centre National de la Recherche Scientifique, Life Science Department, Bordeaux-Valbonne, France

3 Université de Nice-Sophia Antipolis, CNRS, Virtual Biology Lab, Parc Valrose, 06108 Nice, France

4 Institut de Biologia Evolutiva (UPF-CSIC), CEXS-UPF-PRBB, C/Dr Aiguader, 88, Barcelona 08003, Spain

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BMC Evolutionary Biology 2008, 8:330  doi:10.1186/1471-2148-8-330

Published: 9 December 2008

Abstract

Background

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 Homo sapiens. PMCHL1 arose from retroposition of a pro-melanin-concentrating hormone (PMCH) 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 PMCHL1 duplicated in an ancestor of hominids to generate PMCHL2 at the human chromosome 5q13. A complex pattern of spliced and unspliced PMCHL RNAs were found in human brain and testis.

Results

Several novel spliced PMCHL transcripts have been characterized in human testis and fetal brain, identifying an additional exon and novel splice sites. Sequencing of PMCHL 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 brain cadherin (CDH12) 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 PMCHL 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 PMCHL RNA failed to reveal any protein corresponding to VMCH-p8 and protein variants encoded by spliced transcripts.

Conclusion

Our present results improve our knowledge of the gene structure and the evolutionary history of the primate-specific chimeric PMCHL 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.