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Phylogenetic Analysis and in Silico Characterization of the GARS-AIRS-GART Gene which Codes for a tri-Functional Enzyme Protein Involved in de novo Purine Biosynthesis

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Abstract

Human GARS-AIRS-GART encodes a fused tri-functional enzyme protein involved in de novo purine biosynthesis, aberrant function being implicated in Down syndrome and Leukemia. We performed phylogenetic analysis to discern evolutionary relationships and in silico characterization to identify elements potentially important for gene regulation. We report that murine, bovine and chimpanzee sequences are the nearest neighbors of human GARS-AIRS-GART and that endo-duplication of the AIRS protein is restricted to insect orthologs. Convergent evolution of mono-functional bacterial orthologs to bi-functional, partly fused, yeast orthologs is observed from the rooted-NJ tree topology that bears bootstrap values exceeding 9000 in majority of the nodes. Sequence alignments reveal that introns 11–15 of human GARS-AIRS-GART are conserved among vertebrates. An inverse correlation is observed between intron size and intron density without bias for intron position. The generation time of organisms is independent of intron density. Human, bovine and murine sequences possess similar GC content with CpG islands in promoter regions. The long isoforms of cow and chicken transcripts and short isoforms of human, bovine and murine mRNA form energetically stable stem-like structures in the 3′-UTR and may regulate translational stability of GARS-AIRS-GART transcripts. Glycine-rich loops important for enzyme structure and ATP-, folate-binding residues are partially conserved.

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Acknowledgements

Disha Banerjee is the recipient of a Junior Research Fellowship from CSIR grant 27(0131)/04/EMR-II awarded to Krishnadas Nandagopal. The authors thank Mr. Subhrangshu Guhathakurta (Manovikas Kendra Rehabilitation & Research Institute for the Handicapped, Kolkata, India) for technical assistance with the preparation of figures and Dr. T. K. Mukhopadhyay (Department of Zoology, Presidency College, Kolkata, India) for critical reading of the manuscript.

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  1. Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra Rehabilitation and Research Institute for the Handicapped, 482 Madudah, Plot I-24, Sector J, Eastern Metropolitan Bypass, Kolkata, 700107, India

    Disha Banerjee & Krishnadas Nandagopal

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Banerjee, D., Nandagopal, K. Phylogenetic Analysis and in Silico Characterization of the GARS-AIRS-GART Gene which Codes for a tri-Functional Enzyme Protein Involved in de novo Purine Biosynthesis. Mol Biotechnol 42, 306–319 (2009). https://doi.org/10.1007/s12033-009-9160-1

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