Phylogeny of related functions: the case of polyamine biosynthetic enzymes.
Genome annotation requires explicit identification of gene function. This task frequently uses protein sequence alignments with examples having a known function. Genetic drift, co-evolution of subunits in protein complexes and a variety of other constraints interfere with the relevance of alignments. Using a specific class of proteins, it is shown that a simple data analysis approach can help solve some of the problems posed. The origin of ureohydrolases has been explored by comparing sequence similarity trees, maximizing amino acid alignment conservation. The trees separate agmatinases from arginases but suggest the presence of unknown biases responsible for unexpected positions of some enzymes. Using factorial correspondence analysis, a distance tree between sequences was established, comparing regions with gaps in the alignments. The gap tree gives a consistent picture of functional kinship, perhaps reflecting some aspects of phylogeny, with a clear domain of enzymes encoding two types of ureohydrolases (agmatinases and arginases) and activities related to, but different from ureohydrolases. Several annotated genes appeared to correspond to a wrong assignment if the trees were significant. They were cloned and their products expressed and identified biochemically. This substantiated the validity of the gap tree. Its organization suggests a very ancient origin of ureohydrolases. Some enzymes of eukaryotic origin are spread throughout the arginase part of the trees: they might have been derived from the genes found in the early symbiotic bacteria that became the organelles. They were transferred to the nucleus when symbiotic genes had to escape Muller's ratchet. This work also shows that arginases and agmatinases share the same two manganese-ion-binding sites and exhibit only subtle differences that can be accounted for knowing the three-dimensional structure of arginases. In the absence of explicit biochemical data, extreme caution is needed when annotating genes having similarities to ureohydrolases.
Sekowska
Agnieszka
A
Hong Kong University Pasteur Research Centre, Dexter HC Man Building, 8 Sassoon Road, Pokfulam, Hong Kong2.|Regulation of Gene Expression, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France1.
Danchin
Antoine
A
Hong Kong University Pasteur Research Centre, Dexter HC Man Building, 8 Sassoon Road, Pokfulam, Hong Kong2.|Regulation of Gene Expression, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France1.
Risler
Jean-Loup
JL
Genome and Informatics, Université de Versailles-Saint-Quentin, 45 Avenue des Etats Unis, 78035 Versailles Cedex, France3.
D000595:Amino Acid Sequence; D000818:Animals; D001119:Arginase / Q000145:classification / Q000235:genetics; D001412:Bacillus subtilis / Q000201:enzymology / Q000235:genetics; D015317:Biogenic Polyamines / Q000096:biosynthesis*; D000458:Cyanobacteria / Q000201:enzymology / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D019143:Evolution, Molecular; D016480:Helicobacter pylori / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D014512:Ureohydrolases / Q000145:classification / Q000235:genetics*
D015317:Biogenic Polyamines; D014512:Ureohydrolases; D001119:Arginase; C498226:AGMAT protein, human; C019625:agmatinase