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Evolutionary and functional relationships within the DJ1 superfamily
Sourav Bandyopadhyay1, Mark R Cookson
1Laboratory of Neurogenetics, National Institute on Aging, 9000 Rockville Pike, Bethesda, MD 20892, USA. bandys@mail.nih.gov
BMC Evolutionary Biology
|April 9, 2004
Summary
The human DJ-1 protein, linked to Parkinson's disease, likely evolved from bacterial ThiJ kinase. Eukaryotes repurposed this gene for a new function after losing the original thiamine biosynthesis pathway.
Area of Science:
- Evolutionary biology
- Molecular biology
- Biochemistry
Background:
- Protein function is often inferred from sequence homology.
- This method is challenging for large protein superfamilies with diverse functions.
- The DJ-1/ThiJ/PfpI superfamily includes human DJ-1, associated with Parkinson's disease.
Purpose of the Study:
- Investigate sequence homology within the DJ-1/ThiJ/PfpI superfamily.
- Determine the evolutionary origins and potential function of human DJ-1.
Main Methods:
- Comparative sequence analysis of DJ-1/ThiJ/PfpI superfamily members.
- Phylogenetic clustering of orthologs across species.
- Comparison with characterized superfamily members (kinases, proteases).
Main Results:
- Eukaryotic DJ-1 orthologs form a distinct cluster.
- Bacterial ThiJ genes, involved in thiamine biosynthesis, are the most closely related.
- Similarity to proteases is remote, consistent with lack of catalytic triad in crystal structures.
Conclusions:
- Human DJ-1 may have evolved from bacterial ThiJ kinase.
- The kinase function was lost in eukaryotes as thiamine became an essential nutrient.
- The DJ-1 gene was likely co-opted for a novel function in eukaryotes.