Convergent evolution links molybdenum insertase domains with organism-specific sequences

Author: mycolabadmin
10/18/2024
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Summary

Scientists discovered that fungi have uniquely evolved a special way to make molybdenum cofactor, a molecule essential for life. When researchers tried to swap the fungal version with versions from plants or animals, the fungi couldn’t survive properly. A specific 20-amino acid section turned out to be critical for the fungus to use nitrate as food. This finding shows that evolution has created highly specialized solutions for the same biological problem in different organisms.

Background

Molybdenum cofactor (Moco) biosynthesis is a conserved process essential for eukaryotic organisms and embedded in carbon, nitrogen, and sulfur metabolism. Mutations in Moco biosynthesis genes cause fatal genetic disorders including seizures, intellectual disability, and neonatal death in humans. The final two steps of Moco biosynthesis are catalyzed by Mo insertase, which in higher organisms consists of two fused domains linked by a variable linkage region.

Objective

This study investigated the evolutionary significance of Mo insertase gene fusion and the functional importance of organism-specific linkage sequences between the G and E domains. The researchers aimed to understand why Mo insertase genes were repeatedly fused during eukaryotic evolution and whether linkage sequences could be interchanged between species.

Results

Substituting the fungal linkage region with sequences from plants, mammals, or bacteria resulted in Moco deficiency and impaired growth on nitrate medium. Separate expression of G and E domains failed to rescue deficient strains. Stepwise truncation revealed a critical 20-amino acid sequence (A184-G203) essential for fungal growth and Mo insertase function, with structural modeling showing this region forms a helical structure crucial for proper enzyme function.

Conclusion

The study demonstrates that convergently evolved Mo insertase linkage regions are highly species-specific and cannot be interchanged between organisms. The 20-amino acid A184-G203 region is critical for Moco biosynthesis in fungi, likely functioning in substrate channeling or protein-protein interactions rather than direct catalysis. These findings highlight the evolutionary importance of gene fusion and specific sequence composition in eukaryotic Mo insertases.

Published in:Communications Biology,
Study Type:Molecular Biology Research Study,
Source: PMID: 39424966, DOI: 10.1038/s42003-024-07073-w