Abstract
BackgroundBrain-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.ResultsSeveral 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.ConclusionOur 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.
Highlights
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
In order to further precise the exon/intron structure of PMCHL genes and to further investigate the tissue distribution of spliced PMCHL transcripts, we examined the presence of additional RNAs in human testis and cortex Marathon cDNA libraries, as well as in a human fetal prefrontal cortex sample
Which kind of sequences allows invasion by foreign sequences? Which kind of sequences can we find at the segmental duplication boundaries? No clear boundaries specificities are described for segmental duplication except for a significant enrichment in short interspersed elements (SINEs) such as young Alu Y and Alu S sequences and other repeats similar to these involved in Ig heavy chain recombination in pericentromeric and interstitial segmental duplications [2,13,43]
Summary
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. Combination of exon shuffling, retrotransposition and gene promoter fusion have led to genes harbouring completely new structures and expression patterns selectively in the primate lineage (reviewed in [22,23]). These rare events would have been important in shaping human genes found expressed in reproductive organs, as exemplified by the chimeric POTE-actin genes [24], or involved in hominoid brain neurotransmission, as exemplified by the GLUD2 gene [25]
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