Evolutionary diversification and characterization of the eubacterial gene family encoding DXR type II, an alternative isoprenoid biosynthetic enzyme

BMC Evolutionary Biology

Manuel Rodríguez-Concepción³  Victor A Albert²  Félix J Sangari¹  Jordi Pérez-Gil³  Agnieszka Lipska²  Lorenzo Carretero-Paulet⁴ 

[1] Department of Molecular Biology, Universidad de Cantabria and Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), UC-CSIC-SODERCAN, Avda. de los Castros s/n, Santander E-39005, Cantabria, Spain;Institute for Plant Molecular and Cell Biology - IBMCP (CSIC-UPV), Integrative Systems Biology Group, C/ Ingeniero Fausto Elio s/n., Valencia 46022, Spain;Centre for Research in Agricultural Genomics (CRAG), CSIC-IRTA-UAB-UB, Campus UAB, Bellaterra, Barcelona 08193, Spain;Department of Biological Sciences, SUNY-University at Buffalo, North Campus. 109 Cooke Hall, Buffalo, NY 14260, USA

关键词: Functional divergence;    Gene loss;    Horizontal gene transfer;    Isoprenoid metabolism;    DXR-II;   

Others  :  1086485
DOI  :  10.1186/1471-2148-13-180

 received in 2013-05-14, accepted in 2013-08-16,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Carretero-Paulet et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

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