Evolutionary significance of intra-genome duplications on human chromosomes.

Phylogenetic analyses indicated that a series of paralogous gene pairs, found in two extensive regions on human chromosomal bands 6p21.3 and 9q33-34, were created by at least two independent duplications. The duplicated genes on chromosomal band 6p21.3 include the genes for type 11 collagen alpha2 subunit (COL11A2), NOTCH4 (mouse int-3 homologue), 70 kDa heat shock protein (HSPA1A, HSPA1B, and HSPA1L), valyl-tRNA synthetase 2 (VARS2), complement components (C2 and C4), pre-B cell leukemia transcription factor 2 (PBX2), retinoid X receptor beta (RXRB), NAT/RING3, and four other proteins. Their paralogous genes on chromosomal band 9q33-34 are genes for type 5 collagen alpha1 subunit (COL5A1), NOTCH1, 78 kDa glucose-regulated protein (HSPA5), valyl-tRNA synthetase 1 (VARS1), complement component V (C5), PBX3, retinoid X receptor alpha (RXRA), ORFX/RING3L, and others. Among these, the genes for collagen, complement components, NAT/RING3, PBX, and RXR appear to have been duplicated around the time of vertebrate emergence, supporting the idea that they were duplicated simultaneously at that time. Another group of genes that includes NOTCH and HSP appear to have diverged long before that time. A comparison of the physical maps of these two regions revealed that the genes which duplicated in the same period were arranged in almost the same order in the two regions, with the assumption of a few chromosomal rearrangements. We propose a possible model for the evolution of these regions, taking into account the molecular mechanisms of regional duplication, gene duplication, translocation, and inversion. We also propose that a comparative mapping of paralogous genes within the human genome would be useful for identifying new genes.

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