Enrique Morett

Instituto de Biotecnología, UNAM. Ave. Universidad 2001, Col. Chamilpa, Morelos, 62210 Cuernavaca, Morelos, México
emorett@ibt.unam.mx

Prediction of gene function is one of the most challenging tasks in genomic sciences when there is no clear sequence similarity to annotated genes. However, it is even more challenging to assign the correct function to genes that display sequence similarity to genes of unrelated function. Analogous enzymes perform the same biochemical reaction but they are not phylogenetically related, such that it is not possible to identify them by sequence similarity. Here we propose that the vitamin biosynthetic pathways have experienced multiple events of gene loss and recovery of function by unrelated genes, the so-called analogous gene displacement. We carried out an extensive search for the genes that participate in thiamin biosynthetic pathways in the completely sequenced genomes. We show that the great majority of these organisms lack from a few to many orthologues to the Escherichia coli thi genes, despite the fact that they do synthesize thiamin. We searched for the analogous enzymes using gene neighbourhood, coocurrence in operons, identification of regulatory sequences, and a new method based on the anticorrelation of occurrence of genes in the genomes. These approaches resulted in the identification of several possible analogous enzymes in this pathway. Experimental verification confirmed the function of four candidate genes.

• Morett E, Korbel JO, Rajan E, Saab-Rincon G, Olvera L, Olvera M, Schmidt S, Snel B, Bork P. 2003. Systematic discovery of analogous enzymes in thiamin biosynthesis. Nat Biotechnol. 21:790-795.
  
  
• Chaney M, Grande R, Wigneshweraraj SR, Cannon W, Casaz P, Gallegos MT, Schumacher J, Jones S, Elderkin S, Dago AE, Morett E, Buck M. 2001. Binding of transcriptional activators to sigma 54 in the presence of the transition state analog ADP-aluminum fluoride: insights into activator mechanochemical action. Genes Dev. 15:2282-2294.
  
  
• Juarez K, Flores H, Davila S, Olvera L, Gonzalez V, Morett E. 2000. Reciprocal domain evolution within a transactivator in a restricted sequence space. Proc Natl Acad Sci USA. 97:3314-3318.