Phylogenomic analysis of the uracil-DNA glycosylase superfamily

J. Ignacio Lucas-Lledó, Rohan Maddamsetti, Michael Lynch

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The spontaneous deamination of cytosine produces uracil mispaired with guanine in DNA, which will produce a mutation, unless repaired. In all domains of life, uracil-DNA glycosylases (UDGs) are responsible for the elimination of uracil from DNA. Thus, UDGs contribute to the integrity of the genetic information and their loss results in mutator phenotypes. We are interested in understanding the role of UDG genes in the evolutionary variation of the rate and the spectrum of spontaneous mutations. To this end, we determined the presence or absence of the five main UDG families in more than 1,000 completely sequenced genomes and analyzed their patterns of gene loss and gain in eubacterial lineages. We observe nonindependent patterns of gene loss and gain between UDG families in Eubacteria, suggesting extensive functional overlap in an evolutionary timescale. Given that UDGs prevent transitions at G:C sites, we expected the loss of UDG genes to bias the mutational spectrum toward a lower equilibrium G + C content. To test this hypothesis, we used phylogenetically independent contrasts to compare the G + C content at intergenic and 4-fold redundant sites between lineages where UDG genes have been lost and their sister clades. None of the main UDG families present in Eubacteria was associated with a higher G + C content at intergenic or 4-fold redundant sites. We discuss the reasons of this negative result and report several features of the evolution of the UDG superfamily with implications for their functional study. uracil-DNA glycosylase, mutation rate evolution, mutational bias, GC content, DNA repair, mutator gene.

Original languageEnglish (US)
Pages (from-to)1307-1317
Number of pages11
JournalMolecular Biology and Evolution
Volume28
Issue number3
DOIs
StatePublished - Mar 1 2011
Externally publishedYes

Fingerprint

Uracil-DNA Glycosidase
DNA
Base Composition
Genes
gene
Eubacteria
uracil
genes
Uracil
mutation
uracil-DNA glycosylase
analysis
Bacteria
deamination
Deamination
Mutation
cytosine
Cytosine
guanine
Guanine

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics

Cite this

Phylogenomic analysis of the uracil-DNA glycosylase superfamily. / Lucas-Lledó, J. Ignacio; Maddamsetti, Rohan; Lynch, Michael.

In: Molecular Biology and Evolution, Vol. 28, No. 3, 01.03.2011, p. 1307-1317.

Research output: Contribution to journalArticle

Lucas-Lledó, J. Ignacio ; Maddamsetti, Rohan ; Lynch, Michael. / Phylogenomic analysis of the uracil-DNA glycosylase superfamily. In: Molecular Biology and Evolution. 2011 ; Vol. 28, No. 3. pp. 1307-1317.
@article{415a3d7daee74cba9d07a4c8ac0e2030,
title = "Phylogenomic analysis of the uracil-DNA glycosylase superfamily",
abstract = "The spontaneous deamination of cytosine produces uracil mispaired with guanine in DNA, which will produce a mutation, unless repaired. In all domains of life, uracil-DNA glycosylases (UDGs) are responsible for the elimination of uracil from DNA. Thus, UDGs contribute to the integrity of the genetic information and their loss results in mutator phenotypes. We are interested in understanding the role of UDG genes in the evolutionary variation of the rate and the spectrum of spontaneous mutations. To this end, we determined the presence or absence of the five main UDG families in more than 1,000 completely sequenced genomes and analyzed their patterns of gene loss and gain in eubacterial lineages. We observe nonindependent patterns of gene loss and gain between UDG families in Eubacteria, suggesting extensive functional overlap in an evolutionary timescale. Given that UDGs prevent transitions at G:C sites, we expected the loss of UDG genes to bias the mutational spectrum toward a lower equilibrium G + C content. To test this hypothesis, we used phylogenetically independent contrasts to compare the G + C content at intergenic and 4-fold redundant sites between lineages where UDG genes have been lost and their sister clades. None of the main UDG families present in Eubacteria was associated with a higher G + C content at intergenic or 4-fold redundant sites. We discuss the reasons of this negative result and report several features of the evolution of the UDG superfamily with implications for their functional study. uracil-DNA glycosylase, mutation rate evolution, mutational bias, GC content, DNA repair, mutator gene.",
author = "Lucas-Lled{\'o}, {J. Ignacio} and Rohan Maddamsetti and Michael Lynch",
year = "2011",
month = "3",
day = "1",
doi = "10.1093/molbev/msq318",
language = "English (US)",
volume = "28",
pages = "1307--1317",
journal = "Molecular Biology and Evolution",
issn = "0737-4038",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - Phylogenomic analysis of the uracil-DNA glycosylase superfamily

AU - Lucas-Lledó, J. Ignacio

AU - Maddamsetti, Rohan

AU - Lynch, Michael

PY - 2011/3/1

Y1 - 2011/3/1

N2 - The spontaneous deamination of cytosine produces uracil mispaired with guanine in DNA, which will produce a mutation, unless repaired. In all domains of life, uracil-DNA glycosylases (UDGs) are responsible for the elimination of uracil from DNA. Thus, UDGs contribute to the integrity of the genetic information and their loss results in mutator phenotypes. We are interested in understanding the role of UDG genes in the evolutionary variation of the rate and the spectrum of spontaneous mutations. To this end, we determined the presence or absence of the five main UDG families in more than 1,000 completely sequenced genomes and analyzed their patterns of gene loss and gain in eubacterial lineages. We observe nonindependent patterns of gene loss and gain between UDG families in Eubacteria, suggesting extensive functional overlap in an evolutionary timescale. Given that UDGs prevent transitions at G:C sites, we expected the loss of UDG genes to bias the mutational spectrum toward a lower equilibrium G + C content. To test this hypothesis, we used phylogenetically independent contrasts to compare the G + C content at intergenic and 4-fold redundant sites between lineages where UDG genes have been lost and their sister clades. None of the main UDG families present in Eubacteria was associated with a higher G + C content at intergenic or 4-fold redundant sites. We discuss the reasons of this negative result and report several features of the evolution of the UDG superfamily with implications for their functional study. uracil-DNA glycosylase, mutation rate evolution, mutational bias, GC content, DNA repair, mutator gene.

AB - The spontaneous deamination of cytosine produces uracil mispaired with guanine in DNA, which will produce a mutation, unless repaired. In all domains of life, uracil-DNA glycosylases (UDGs) are responsible for the elimination of uracil from DNA. Thus, UDGs contribute to the integrity of the genetic information and their loss results in mutator phenotypes. We are interested in understanding the role of UDG genes in the evolutionary variation of the rate and the spectrum of spontaneous mutations. To this end, we determined the presence or absence of the five main UDG families in more than 1,000 completely sequenced genomes and analyzed their patterns of gene loss and gain in eubacterial lineages. We observe nonindependent patterns of gene loss and gain between UDG families in Eubacteria, suggesting extensive functional overlap in an evolutionary timescale. Given that UDGs prevent transitions at G:C sites, we expected the loss of UDG genes to bias the mutational spectrum toward a lower equilibrium G + C content. To test this hypothesis, we used phylogenetically independent contrasts to compare the G + C content at intergenic and 4-fold redundant sites between lineages where UDG genes have been lost and their sister clades. None of the main UDG families present in Eubacteria was associated with a higher G + C content at intergenic or 4-fold redundant sites. We discuss the reasons of this negative result and report several features of the evolution of the UDG superfamily with implications for their functional study. uracil-DNA glycosylase, mutation rate evolution, mutational bias, GC content, DNA repair, mutator gene.

UR - http://www.scopus.com/inward/record.url?scp=79952147727&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952147727&partnerID=8YFLogxK

U2 - 10.1093/molbev/msq318

DO - 10.1093/molbev/msq318

M3 - Article

C2 - 21135150

AN - SCOPUS:79952147727

VL - 28

SP - 1307

EP - 1317

JO - Molecular Biology and Evolution

JF - Molecular Biology and Evolution

SN - 0737-4038

IS - 3

ER -