Hominid history and chimeric genes

n° 392 - April 2001

"What are the genetic events associated with the emergence of new functions in higher primates?" This is the fundamental question being addressed by Jean-Louis Nahon and colleagues at the "Institut de pharmacologie moléculaire et cellulaire" (Institute of Molecular and Cellular Pharmacology) in Valbonne (CNRS-Université de Nice-Sophia-Antipolis). They decided to investigate the molecular history of PMCHL1 and PMCHL2, two chimeric human genes that both derived from the melanin-concentrating hormone (MCH) gene. Currently scientists believe that new genes occur through complex processes involving exon shuffling, retrotransposition, and gene duplication. The "authentic" human MCH gene maps to chromosome 12 and encodes a neuropeptide molecule, while PMCHL1 and PMCHL2 map respectively to chromosome 5p14 and 5q13 and encode putative nuclear proteins. Strikingly, only the PMCHL1 gene appears to be transcribed in the human brain, whereas both genes are active in other organs. The CNRS researchers performed a detailed structural, expression and phylogenetic analysis of the PMCHL genes located on the two arms of chromosome 5. They concluded that the PMCHL1 gene was created nearly 25 million years ago (Mya) by a complex mechanism of exon shuffling through retrotransposition of an antisense MCH messenger RNA coupled to de novo creation of splice sites. The PMCHL2 gene arose 5 to 10 Mya by a chromosomal duplication event involving a large DNA region encompassing the PMCHL1 locus. This work gives insights into the remarkable molecular and genetic events that went into creating the Hominid-specific PMCHL genes. The laboratory is currently investigating the expression pattern of PMCHL1 in the central nervous system of various primates, including humans, and its possible contribution to the evolution of novel human brain functions.

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