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"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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