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 d uplicated genes on chromosomal band 6p21.3 include the genes for type 11 collagen alpha 2 subunit (COL11A2), NOTCH4 (mouse int-3 homologue), 70 kDa heat shock protein (HSPA1A, HSPA1B, and HSPA1L), valyl-tRNA sy nthetase 2 (VARS2), complement components (C2 and C4), pre-B cell leuk emia transcription factor 2 (PBX2), retinoid X receptor beta (RXRB), N AT/RING3, and four other proteins. Their paralogous genes on chromosom al band 9q33-34 are genes for type 5 collagen alpha 1 subunit (COL5A1) , NOTCH1, 78 kDa glucose-regulated protein (HSPA5), valyl-tRNA synthet ase 1 (VARS1), complement component V (C5), PBX3, retinoid X receptor alpha (RXRA), ORFX/RING3L, and others. Among these, the genes for coll agen, complement components, NAT/RING3, PBX, and RXR appear to have be en duplicated around the time of vertebrate emergence, supporting the idea that they were duplicated simultaneously at that time. Another gr oup of genes that includes NOTCH and HSP appear to have diverged long before that time. A comparison of the physical maps of these two regio ns revealed that the genes which duplicated in the same period were ar ranged in almost the same order in the two regions, with the assumptio n of a few chromosomal rearrangements. We propose a possible model for the evolution of these regions, taking into account the molecular mec hanisms of regional duplication, gene duplication, translocation, and inversion. We also propose that a comparative mapping of paralogous ge nes within the human genome would be useful for identifying new genes. (C) 1997 Elsevier Science B.V.