Conference Paper Abstract/Meeting Abstract ()
George S & Leaver M (2006) Xenobiotic conjugation in fish: Organisation and diversity of phase 2 genes revealed by genome sequence and EST data (Meeting Abstract).
The UDP-glucuronosyl transferase (UGT) and glutathione s-transferase (GST) multigene families of enzymes of mammals exhibit a wide substrate specificity for detoxification of xenobiotic compounds. Whilst enzyme purification studies have revealed the presence of multiple isoforms in fish, few have been characterised. With the recent availability of extensive genome sequence and EST data for puffer and zebrafish we have now been able to identify homologues of many of the mammalian genes which will lead the way to their heterologous expression and the determination of their catalytic capabilities. GST genes with homology to classes Alpha, Kappa, Mu, Omega, Pi, Theta, fish GST-A class and microsomal GST enzymes were identified in all species confirming their ancient lineage and implying their broad functional capacity. Multiple fish UGT genes were also identified, supporting the participation of distinct isoforms catalysing the variety of conjugation activities observed in fish. In mammals, the UGT1 family genes display duplication of the aglycone specific exon 1 and alternative splicing to produce different isoforms with differential specificity towards bilirubin, thyroid hormones, planar and non-planar phenols. Our analysis shows that the homologous UGTs of zebrafish also exhibit duplication of exon 1's and alternative splicing but that they represent a distinct clade from the mammalian genes. Most interestingly, the UGT Family 1 genes of Puffer do not show this phenomenon and appear to be duplicated in their entirety. This would imply that UGT1B1 of puffer (and plaice) are of ancient lineage and that duplication of exon 1's of the Cyprinid and Mammalian UGT1 family genes were independent evolutionary events. Support funding was provided by NERC.
|Authors||George Stephen, Leaver Michael|
Marine Environmental Research: Volume 62, Issue Supplement 1 (2006)