Life without dUTPase

TL;DR

This study reveals that many bacteria and archaea lack the dUTPase gene, challenging previous assumptions, and identifies alternative survival strategies that allow these organisms to maintain DNA integrity despite the absence of this enzyme.

Contribution

It systematically analyzes microbial genomes and uncovers multiple independent losses of the dUTPase gene, proposing novel survival mechanisms in these organisms.

Findings

Many bacterial and archaeal species lack dUTPase genes.

Loss of dUTPase has occurred multiple times evolutionarily.

Organisms employ alternative strategies like UNG inhibition or phage-derived enzymes.

Abstract

Fine-tuned regulation of the cellular nucleotide pools is indispensable for faithful replication of DNA. The genetic information is also safeguarded by DNA damage recognition and repair processes. Uracil is one of the most frequently occurring erroneous base in DNA; it can arise from cytosine deamination or thymine-replacing incorporation. Two enzyme families are primarily involved in keeping DNA uracil-free: dUTPases that prevent thymine-replacing incorporation and uracil-DNA glycosylases that excise uracil from DNA and initiate uracil-excision repair. Both dUTPase and the most efficient uracil-DNA glycosylase UNG is thought to be ubiquitous in free-living organisms. In the present work, we have systematically investigated the genotype of deposited fully sequenced bacterial and Archaeal genomes. Surprisingly, we have found that in contrast to the generally held opinion, a wide number of bacterial and Archaeal species lack the dUTPase gene(s). The dut- genotype is present in diverse bacterial phyla indicating that loss of this (or these) gene(s) has occurred multiple times during evolution. We have identified several survival strategies in lack of dUTPases: i) simultaneous lack or inhibition of UNG, ii) acquisition of a less dUTP-specific sanitizing nucleotide pyrophosphatase, and iii) supply of dUTPase from bacteriophages. Our data indicate that several unicellular microorganisms may efficiently cope with a dut- genotype potentially leading to an unusual uracil-enrichment in their genomic DNA.