Multiple Gene Duplication and Rapid Evolution in the groEL Gene: Functional Implications

Abstract

Abstract. The chaperonins, GroEL and GroES, are present ubiquitously and provide a paradigm in the understanding of assisted protein folding. Due to its essentiality of function, GroEL exhibits high sequence conservation across species. Complete genome sequencing has shown the occurrence of duplicate or multiple copies of groEL genes in bacteria such as Mycobacterium tuberculosis and Corynebacterium glutamicum. Monophyly of each bacterial clade in the phylogenetic tree generated for the GroEL protein suggests a lineage-specific duplication. The duplicated groEL gene in Actinobacteria is not accompanied by the operonic groES despite the presence of upstream regulatory elements. Our analysis suggests that in these bacteria the duplicated groEL genes have undergone rapid evolution and divergence to function in a GroES-independent manner. Evaluation of multiple sequence alignment demonstrates that the duplicated genes have acquired mutations at functionally significant positions including those involved in substrate binding, ATP binding, and GroES binding and those involved in inter-ring and intra-ring interactions. We propose that the duplicate groEL genes in different bacterial clades have evolved independently to meet specific requirements of each clade. We also propose that the groEL gene, although essential and conserved, accumulates nonconservative substitutions to exhibit structural and functional variations.

Homologous cpn60 genes in Rhizobium leguminosarum are not functionally equivalent

“…It is likely therefore that the multiple groEL homologues in Rhizobia have arisen by a mixture of gene duplication, speciation, and horizontal gene transfer. Because of the high similarity between the genes, the details of this are unlikely to be decipherable, a conclusion also reached in a recent detailed analysis of GroEL phylogeny (Goyal et al 2006).…”

Multiple chaperonins in bacteria—novel functions and non-canonical behaviors

“…The existence of multiple groEL genes opens up several hypotheses on their function and evolution and on the distribution of the substrates. The organism expressing multiple GroELs might benefit either from the dosage effect of multiple chaperonins (Kondrashov and Kondrashov 2006) or from the functional divergence of different chaperonins (Goyal et al 2006). The former appears unlikely since the levels of chaperonins are always high in the cell.…”

“…Consequent to their hampered oligomeric nature, mycobacterial GroELs failed as chaperones: displayed weak ATPase activities and failed in either refolding or preventing aggregation of the denatured polypeptides. Furthermore, evolutionary studies on Mtb groEL sequences have suggested rapid evolution of the groEL1 gene (Goyal et al 2006) and that the difference in the rates of evolution between GroEL1 and GroEL2 has been proposed to be due to differential interaction of these chaperonins with the host immune system (Hughes 1993). Although these studies have principally employed biochemical tools on purified proteins and convincingly demonstrated the inability of Mtb GroELs to act as chaperones, further genetic studies on these chaperonin genes have provided evidence towards the hypothesis that Mtb GroELs are inactive as chaperonins (Kumar et al 2009;Henderson et al 2010;Kumar and Mande 2011).…”

Taxonomic analysis of Sorangium strains based on HSP60 and 16S rRNA gene sequences and morphology

“…HSP60 is ubiquitous and highly conserved in bacteria, and thus is being used more frequently to infer eubacterial phylogenies (Karlin & Brocchieri, 2000). The groEL gene is present as a single copy in most bacterial species, but two or more copies are found in some bacteria (Goyal et al, 2006). In this paper, two different HSP60 genes (groEL1 and groEL2) were amplified from Sorangium strains.…”