Journal of Biological Chemistry
Volume 273, Issue 4, 23 January 1998, Pages 1923-1932
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CARBOHYDRATES, LIPIDS, AND OTHER NATURAL PRODUCTS
Characterization and Molecular Evolution of a Vertebrate Hyaluronan Synthase Gene Family*

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The three mammalian hyaluronan synthase (HAS) genes and the related Xenopus laevis gene,DG42, belong to a larger evolutionarily conserved vertebrate HAS gene family. We have characterized additional vertebrate HAS genes from chicken (chas2 and chas3) andXenopus (xhas2, xhas3, and a uniqueXenopus HAS-related sequence, xHAS-rs). Genomic structure analyses demonstrated that all vertebrate HAS genes share at least one exon-intron boundary, suggesting that they evolved from a common ancestral gene. Furthermore, the Has2 andHas3 genes are identical in structure, suggesting that they arose by a gene duplication event early in vertebrate evolution. Significantly, similarities in the genomic structures of the mouseHas1 and Xenopus DG42 genes strongly suggest that they are orthologues. Northern analyses revealed a similar temporal expression pattern of HAS genes in developing mouse andXenopus embryos. Expression of mouse Has2, Has3, andXenopus Has1 (DG42) led to hyaluronan biosynthesis in transfected mammalian cells. However, only mouse Has2 and Has3 expressing cells formed significant hyaluronan-dependent pericellular coats in culture, implying both functional similarities and differences among vertebrate HAS enzymes. We propose that vertebrate hyaluronan biosynthesis is regulated by a comparatively ancient gene family that has arisen by sequential gene duplication and divergence.

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*

This work was supported by individual National Research Service Award 1 F32 HL09311-01 (to A. P. S.), by American Heart Association, Arizona Affiliate, Beginning Grant-in-aid Fellowship AZGB-19-96 (to A. P. S.), and by funds from the Mayo Foundation for Education and Research.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) AF015780 (X. laevis HAS-related sequence, xHAS-rscDNA), AF015779 (X. laevis xHas2 partial cDNA), AF015778 (xHas3 partial cDNA), AF015776 (chicken, G. gallus, chas2 partial cDNA), and AF015777 (chicken chas3 partial cDNA).