Extensive domain shuffling in transcription regulators of DNA viruses and implications for the origin of fungal APSES transcription factors.
BACKGROUND
Viral DNA-binding proteins have served as good models to study the biochemistry of transcription regulation and chromatin dynamics. Computational analysis of viral DNA-binding regulatory proteins and identification of their previously undetected homologs encoded by cellular genomes might lead to a better understanding of their function and evolution in both viral and cellular systems.


RESULTS
The phyletic range and the conserved DNA-binding domains of the viral regulatory proteins of the poxvirus D6R/N1R and baculoviral Bro protein families have not been previously defined. Using computational analysis, we show that the amino-terminal module of the D6R/N1R proteins defines a novel, conserved DNA-binding domain (the KilA-N domain) that is found in a wide range of proteins of large bacterial and eukaryotic DNA viruses. The KilA-N domain is suggested to be homologous to the fungal DNA-binding APSES domain. We provide evidence for the KilA-N and APSES domains sharing a common fold with the nucleic acid-binding modules of the LAGLIDADG nucleases and the amino-terminal domains of the tRNA endonuclease. The amino-terminal module of the Bro proteins is another, distinct DNA-binding domain (the Bro-N domain) that is present in proteins whose domain architectures parallel those of the KilA-N domain-containing proteins. A detailed analysis of the KilA-N and Bro-N domains and the associated domains points to extensive domain shuffling and lineage-specific gene family expansion within DNA virus genomes.


CONCLUSIONS
We define a large class of novel viral DNA-binding proteins and their cellular homologs and identify their domain architectures. On the basis of phyletic pattern analysis we present evidence for a probable viral origin of the fungus-specific cell-cycle regulatory transcription factors containing the APSES DNA-binding domain. We also demonstrate the extensive role of lineage-specific gene expansion and domain shuffling, within a limited set of approximately 24 domains, in the generation of the diversity of virus-specific regulatory proteins.
Iyer
Lakshminarayan M
LM
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. aravind@ncbi.nlm.nih.gov
Koonin
Eugene V
EV
Aravind
L
L
D000595:Amino Acid Sequence / Q000235:genetics; D016367:Baculoviridae / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D017124:Conserved Sequence / Q000235:genetics; D004267:DNA Viruses / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000235:genetics*; D005809:Genes, Regulator / Q000235:genetics*; D011212:Poxviridae / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C087700:N1R protein, Rabbit fibroma virus; D014157:Transcription Factors; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins