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Flavin-dependent thymidylate synthase X limits chromosomal DNA replication.

Frédéric Escartin¹, Stéphane Skouloubris, Ursula Liebl

¹Laboratoire d'Optique et Biosciences, Centre National de la Recherche Scientifique, Ecole Polytechnique, F-91128 Palaiseau, France.

Proceedings of the National Academy of Sciences of the United States of America

|July 16, 2008

Summary

Differences in thymidylate synthase enzymes (ThyX and ThyA) impact DNA replication speed and prokaryotic genome size. The efficient ThyA enzyme supports larger genomes, suggesting thymidylate metabolism limits genome expansion and influences evolution.

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Area of Science:

Biochemistry
Evolutionary Biology
Genomics

Background:

Thymidylate synthases (ThyX and ThyA) are crucial enzymes for synthesizing deoxythymidine monophosphate (dTMP), an essential DNA precursor.
Differences in the catalytic efficiency between ThyX and ThyA may have implications for cellular processes and genome evolution.

Purpose of the Study:

To investigate the impact of varying thymidylate synthase catalytic efficiencies on prokaryotic genome evolution.
To determine if DNA replication speed is influenced by the type of thymidylate synthase present.

Main Methods:

Comparative analysis of DNA replication speeds in bacteria and archaea possessing either ThyX or ThyA.
Statistical analysis of over 400 prokaryotic genomes to correlate enzyme type with genome size.
Examination of gene replacement events involving ThyX and ThyA.

Main Results:

Prokaryotes with the less efficient ThyX enzyme exhibit DNA replication speeds up to 10-fold slower than those with the more efficient ThyA.
ThyA proteins are statistically favored in species with larger genomes, indicating thymidylate metabolism as a potential constraint on genome expansion.
ThyX and ThyA are involved in frequent gene replacement events, highlighting their dynamic role in prokaryotic evolution.

Conclusions:

The catalytic efficiency of thymidylate synthases significantly influences prokaryotic DNA replication rates and genome size.
Thymidylate metabolism acts as a key factor modulating prokaryotic genome expansion and evolution.
Enhanced kinetic efficiency in thymidylate synthesis may have contributed to the evolutionary potential of prokaryotes.