Molecular Biology and Evolution, Vol 15, 196-214, Copyright © 1998 by Society for Molecular Biology and Evolution
A Viale, C Ortola, F Richard, P Vernier, F Presse, S Schilling, B Dutrillaux and JL Nahon
Two related but distinct melanin-concentrating hormone (MCH) gene systems,
i.e., the authentic and variant genes, have been characterized in the
human, while only a single MCH gene has been found in the rat. We
previously established that the variant gene corresponds to exon-I- deleted
copies of the authentic gene mapped on chromosomes 5 and 12, respectively.
In this report, we examined the expression of the authentic and variant MCH
genes in the human brain. Mature mRNAs of the authentic MCH gene appeared
to be predominantly expressed in the hypothalamus, whereas putative
unprocessed transcripts of the variant MCH gene were found in other brain
areas but not in the hypothalamus. Several products of the variant MCH gene
were identified by RACE-PCR in the fetal human brain. One of these
transcripts encoded a putative protein of 72 amino acids, while another
transcript may potentially generate a protein of 35 amino acids.
Thereafter, we explored the question of MCH gene transposition during
Primate evolution. Southern blotting, PCR analyses using several genomic
DNAs of Primates, and in situ hybridization on metaphase chromosomes led us
to define at least three types of genetic events associated with the
emergence of the variant MCH gene: (1) translocation of an exon II-exon III
copy of the authentic MCH gene onto the equivalent of the human chromosome
5p arm of Anthropoidea ancestors (between 25 and 55 MYA); (2) exon II
truncation and mutations before divergence of the Hylobatidae (about 15
MYA); and (3) duplication of the variant gene on the equivalent of the
human chromosome 5p and 5q arms in the Hominidae, i.e., 5-10 MYA. Taken
together, these results support the hypothesis that transposition/gene
rearrangement processes could underlie the evolutionary emergence of new
MCH-related genes expressed differentially in the brains of higher
Primates, illustrating the concept of genes "in search of function" instead
of true "pseudogenes."
ORIGINAL ARTICLE
Emergence of a brain-expressed variant melanin-concentrating hormone gene during higher primate evolution: a gene "in search of a function"
Institut de Pharmacologie Moleculaire et Cellulaire, CNRS, Valbonne, France.
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