Evolutionary diversification and characterization of the eubacterial gene family encoding DXR type II, an alternative isoprenoid biosynthetic enzyme
Carretero-Paulet, Lorenzo (Instituto de Biologia Molecular y Celular de Plantas (València, Espanya))
Lipska, Agnieszka (Instituto de Biologia Molecular y Celular de Plantas (València, Espanya))
Pérez-Gil, Jordi (Centre de Recerca en Agrigenòmica)
Sangari, Félix J. (Universidad de Cantabria. Departamento de Biología Molecular)
Albert, Victor A. (Instituto de Biologia Molecular y Celular de Plantas (València, Espanya))
Rodríguez Concepción, Manuel (Centre de Recerca en Agrigenòmica)

Date:	2013
Abstract:	Background: isoprenoids constitute a vast family of natural compounds performing diverse and essential functions in all domains of life. In most eubacteria, isoprenoids are synthesized through the methylerythritol 4-phosphate (MEP) pathway. The production of MEP is usually catalyzed by deoxyxylulose 5-phosphate reductoisomerase (DXR-I) but a few organisms use an alternative DXR-like enzyme (DXR-II). - Results: searches through 1498 bacterial complete proteomes detected 130 sequences with similarity to DXR-II. Phylogenetic analysis identified three well-resolved clades: the DXR-II family (clustering 53 sequences including eleven experimentally verified as functional enzymes able to produce MEP), and two previously uncharacterized NAD(P)-dependent oxidoreductase families (designated DLO1 and DLO2 for DXR-II-like oxidoreductases 1 and 2). Our analyses identified amino acid changes critical for the acquisition of DXR-II biochemical function through type-I functional divergence, two of them mapping onto key residues for DXR-II activity. DXR-II showed a markedly discontinuous distribution, which was verified at several levels: taxonomic (being predominantly found in Alphaproteobacteria and Firmicutes), metabolic (being mostly found in bacteria with complete functional MEP pathways with or without DXR-I), and phenotypic (as no biological/phenotypic property was found to be preferentially distributed among DXR-II-containing strains, apart from pathogenicity in animals). By performing a thorough comparative sequence analysis of GC content, 3:1 dinucleotide frequencies, codon usage and codon adaptation indexes (CAI) between DXR-II sequences and their corresponding genomes, we examined the role of horizontal gene transfer (HGT), as opposed to an scenario of massive gene loss, in the evolutionary origin and diversification of the DXR-II subfamily in bacteria. - Conclusions: our analyses support a single origin of the DXR-II family through functional divergence, in which constitutes an exceptional model of acquisition and maintenance of redundant gene functions between non-homologous genes as a result of convergent evolution. Subsequently, although old episodic events of HGT could not be excluded, the results supported a prevalent role of gene loss in explaining the distribution of DXR-II in specific pathogenic eubacteria. Our results highlight the importance of the functional characterization of evolutionary shortcuts in isoprenoid biosynthesis for screening specific antibacterial drugs and for regulating the production of isoprenoids of human interest.
Grants:	Ministerio de Ciencia e Innovación BIO2011-23680 Ministerio de Ciencia e Innovación BFU2011-25658 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-26
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	DXR-II ; Isoprenoid metabolism ; Horizontal gene transfer ; Gene loss ; Functional divergence
Published in:	BMC evolutionary biology, Vol. 13 (2013) , art. 180, ISSN 1471-2148

DOI: 10.1186/1471-2148-13-180
PMID: 24004839

18 p, 2.0 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Experimental sciences > CRAG (Centre for Research in Agricultural Genomics)
Articles > Research articles
Articles > Published articles