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Glutamine synthetase sequence evolution in the mycobacteria and their use as molecular markers for Actinobacteria speciation.

Hayward D, van Helden PD, Wiid IJ - BMC Evol. Biol. (2009)

Bottom Line: Intriguingly, previous reports have shown that only one copy (glnA1) is essential for growth in M. tuberculosis, while the other copies (glnA2, glnA3 and glnA4) are not.In this report it is shown that the glnA1 and glnA2 encoded glutamine synthetase sequences were inherited from an Actinobacteria ancestor, while the glnA4 and glnA3 encoded GS sequences were sequentially acquired during Actinobacteria speciation.Different selective pressures by the ecological niche that the organisms occupy may influence the sequence evolution of glnA1 and glnA2 and thereby affecting phylogenies based on the protein sequences they encode.

View Article: PubMed Central - HTML - PubMed

Affiliation: DST/NRF Centre for Excellence in Biomedical Tuberculosis Research, US/MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Health Sciences - Stellenbosch University, South Africa. dh@sun.ac.za

ABSTRACT

Background: Although the gene encoding for glutamine synthetase (glnA) is essential in several organisms, multiple glnA copies have been identified in bacterial genomes such as those of the phylum Actinobacteria, notably the mycobacterial species. Intriguingly, previous reports have shown that only one copy (glnA1) is essential for growth in M. tuberculosis, while the other copies (glnA2, glnA3 and glnA4) are not.

Results: In this report it is shown that the glnA1 and glnA2 encoded glutamine synthetase sequences were inherited from an Actinobacteria ancestor, while the glnA4 and glnA3 encoded GS sequences were sequentially acquired during Actinobacteria speciation. The glutamine synthetase sequences encoded by glnA4 and glnA3 are undergoing reductive evolution in the mycobacteria, whilst those encoded by glnA1 and glnA2 are more conserved.

Conclusion: Different selective pressures by the ecological niche that the organisms occupy may influence the sequence evolution of glnA1 and glnA2 and thereby affecting phylogenies based on the protein sequences they encode. The findings in this report may impact the use of similar sequences as molecular markers, as well as shed some light on the evolution of glutamine synthetase in the mycobacteria.

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Related in: MedlinePlus

Multiple protein sequence alignment of the M. tuberculosis glnA encoded sequences shows the amount of variation between these proteins. Identical amino acid sequences are blocked; the insert sequence distinguishing GSIβ are in bold type and the active site tyrosine (position 429) is indicated in red.
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Figure 4: Multiple protein sequence alignment of the M. tuberculosis glnA encoded sequences shows the amount of variation between these proteins. Identical amino acid sequences are blocked; the insert sequence distinguishing GSIβ are in bold type and the active site tyrosine (position 429) is indicated in red.

Mentions: This finding was unexpected, since the glnA4-encoded GS sequence has a conserved tyrosine residue in the adenylylation region of the GS sequence, suggesting that it may rather be derived from glnA1 and would encode a GSIβ enzyme. Therefore the structural relationships between the GS protein sequences encoded by the four M. tuberculosis glnA genes were investigated by aligning the glnA1 (Rv2220; 478 amino acids), glnA2 (Rv2222; 446 amino acids), glnA3 (Rv1878; 450 amino acids) and glnA4 (Rv2860c; 457 amino acids) -protein sequences according to maximum probability of amino acid identities (Figure 4). Inspection of the aligned protein sequences of the four M. tuberculosis glnA sequences (Figure 4) showed differences in functional regions that separate the GSI and GSII protein families. This data reflects a low level of similarity between the GS sequences due to the low level of sequence conservation in regions containing putative functional domains, notably those that might be involved in the formation of the GS-catalytic site [23]. Furthermore, the protein sequences encoded by glnA2, glnA3 and glnA4 lack the insert sequence that is used to identify GSIβ sequences [5]. In addition, the tyrosine residue in the glnA1 protein sequence involved in post-translational regulation of GSIβ through adenylylation [24] is situated in a run of amino acids that is not conserved in the other three proteins. Therefore the tyrosine residue present in the glnA4-encoded GS sequence might not be subjected to post-transcriptional regulation by adenylylation, which indicates that the protein sequences encoded by the glnA3 and glnA4 genes are of the type II GS family. This observation supports the phylogenetic analysis which indicated that the glnA3 and glnA4 protein sequences are related to or may have been derived from the glnA2 protein sequence.


Glutamine synthetase sequence evolution in the mycobacteria and their use as molecular markers for Actinobacteria speciation.

Hayward D, van Helden PD, Wiid IJ - BMC Evol. Biol. (2009)

Multiple protein sequence alignment of the M. tuberculosis glnA encoded sequences shows the amount of variation between these proteins. Identical amino acid sequences are blocked; the insert sequence distinguishing GSIβ are in bold type and the active site tyrosine (position 429) is indicated in red.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2667176&req=5

Figure 4: Multiple protein sequence alignment of the M. tuberculosis glnA encoded sequences shows the amount of variation between these proteins. Identical amino acid sequences are blocked; the insert sequence distinguishing GSIβ are in bold type and the active site tyrosine (position 429) is indicated in red.
Mentions: This finding was unexpected, since the glnA4-encoded GS sequence has a conserved tyrosine residue in the adenylylation region of the GS sequence, suggesting that it may rather be derived from glnA1 and would encode a GSIβ enzyme. Therefore the structural relationships between the GS protein sequences encoded by the four M. tuberculosis glnA genes were investigated by aligning the glnA1 (Rv2220; 478 amino acids), glnA2 (Rv2222; 446 amino acids), glnA3 (Rv1878; 450 amino acids) and glnA4 (Rv2860c; 457 amino acids) -protein sequences according to maximum probability of amino acid identities (Figure 4). Inspection of the aligned protein sequences of the four M. tuberculosis glnA sequences (Figure 4) showed differences in functional regions that separate the GSI and GSII protein families. This data reflects a low level of similarity between the GS sequences due to the low level of sequence conservation in regions containing putative functional domains, notably those that might be involved in the formation of the GS-catalytic site [23]. Furthermore, the protein sequences encoded by glnA2, glnA3 and glnA4 lack the insert sequence that is used to identify GSIβ sequences [5]. In addition, the tyrosine residue in the glnA1 protein sequence involved in post-translational regulation of GSIβ through adenylylation [24] is situated in a run of amino acids that is not conserved in the other three proteins. Therefore the tyrosine residue present in the glnA4-encoded GS sequence might not be subjected to post-transcriptional regulation by adenylylation, which indicates that the protein sequences encoded by the glnA3 and glnA4 genes are of the type II GS family. This observation supports the phylogenetic analysis which indicated that the glnA3 and glnA4 protein sequences are related to or may have been derived from the glnA2 protein sequence.

Bottom Line: Intriguingly, previous reports have shown that only one copy (glnA1) is essential for growth in M. tuberculosis, while the other copies (glnA2, glnA3 and glnA4) are not.In this report it is shown that the glnA1 and glnA2 encoded glutamine synthetase sequences were inherited from an Actinobacteria ancestor, while the glnA4 and glnA3 encoded GS sequences were sequentially acquired during Actinobacteria speciation.Different selective pressures by the ecological niche that the organisms occupy may influence the sequence evolution of glnA1 and glnA2 and thereby affecting phylogenies based on the protein sequences they encode.

View Article: PubMed Central - HTML - PubMed

Affiliation: DST/NRF Centre for Excellence in Biomedical Tuberculosis Research, US/MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Health Sciences - Stellenbosch University, South Africa. dh@sun.ac.za

ABSTRACT

Background: Although the gene encoding for glutamine synthetase (glnA) is essential in several organisms, multiple glnA copies have been identified in bacterial genomes such as those of the phylum Actinobacteria, notably the mycobacterial species. Intriguingly, previous reports have shown that only one copy (glnA1) is essential for growth in M. tuberculosis, while the other copies (glnA2, glnA3 and glnA4) are not.

Results: In this report it is shown that the glnA1 and glnA2 encoded glutamine synthetase sequences were inherited from an Actinobacteria ancestor, while the glnA4 and glnA3 encoded GS sequences were sequentially acquired during Actinobacteria speciation. The glutamine synthetase sequences encoded by glnA4 and glnA3 are undergoing reductive evolution in the mycobacteria, whilst those encoded by glnA1 and glnA2 are more conserved.

Conclusion: Different selective pressures by the ecological niche that the organisms occupy may influence the sequence evolution of glnA1 and glnA2 and thereby affecting phylogenies based on the protein sequences they encode. The findings in this report may impact the use of similar sequences as molecular markers, as well as shed some light on the evolution of glutamine synthetase in the mycobacteria.

Show MeSH
Related in: MedlinePlus