How genes with newly characterized functions originate remains a fundamental question. PMCHL1 and PMCHL2 , two chimeric genes derived from the melanin-concentrating hormone ( MCH ) gene, offer an opportunity to examine such an issue in the human lineage. Detailed structural, expression, and phylogenetic analysis showed that the PMCHL1 gene was created near 25 million years ago (Ma) by a complex mechanism of exon shuffling through retrotransposition of an antisense MCH messenger RNA coupled to de novo creation of splice sites. PMCHL2 arose 5 to 10 Ma by an event of duplication involving a large chromosomal region encompassing the PMCHL1 locus. The RNA expression patterns of those chimeric genes suggest that they have been submitted to strong regulatory constraints during primate evolution.

Recent analyses of the structure of pericentromeric and subtelomeric regions have revealed that these particular regions of human chromosomes are often composed of blocks of duplicated genomic segments that have been associated with rapid evolutionary turnover among the genomes of closely related primates. In the present study, we show that euchromatic regions of human chromosome 5-5p14, 5p13, 5q13, 5q15-5q21-also display such an accumulation of segmental duplications. The structure, organization and evolution of those primate-specific sequences were studied in detail by combining in silico and comparative FISH analyses on human, chimpanzee, gorilla, orangutang, macaca, and capuchin chromosomes. Our results lend support to a two-step model of transposition duplication in the euchromatic regions, with a founder insertional event at the time of divergence between Platyrrhini and Catarrhini (25-35 million years ago) and an apparent burst of interand intrachromosomal duplications in the Hominidae lineage. Furthermore, phylogenetic analysis suggests that the chronology and, likely, molecular mechanisms, differ regarding the region of primary insertion-euchromatic versus pericentromeric regions. Lastly, we show that as their counterparts located near the heterochromatic region, the euchromatic segmental duplications have consistently reshaped their region of insertion during primate evolution, creating putative mosaic genes, and they are obvious candidates for causing ectopic rearrangements that have contributed to evolutionary/genomic instability. There is compelling evidence that gene duplication and transposition events have played essential roles during vertebrate evolution (Brosius 1999a,b;Patthy 1999;Long 2001;Friedman and Hughes 2001a;McLysaght et al. 2002). However, the importance of such evolutionary mechanisms is not restricted to ancient times. The initial sequencing and analysis of the human genome, in combination with previously published reports, have revealed that our genome is constituted of a remarkably complex pattern of both ancient and recent duplications (Lander et al. 2001;Bailey et al. 2002a). It is now estimated that ∼5% (probably more) of our genetic material is composed of duplicated genomic segments that have emerged during the past 35 million years of primate evolution. These blocks (termed segmental duplications) range in size from a few kilobases to hundreds of kilobases, and share a high degree of sequence identity (>90%). In contrast to whole-genome polyploidization events, segmental duplications have originated from the duplicative transpositions of small portions of chromosomal material, often containing intron-exon structure of known genes, and tend to be localized in pericentromeric and subtelomeric regions (for review, see In earliest studies (Viale et al. 1998(Viale et al. , 2000

No abstract

No abstract