Adaptive Evolution of a Stress Response Protein

• Published in: PloS one Vol. 2; no. 10; p. e1003
• Main Authors: Little, Tom J., Nelson, Lenny, Hupp, Ted
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.10.2007; Public Library of Science (PLoS)
• Subjects: Amino Acid Sequence; Amino acids; Analysis; Animals; Bioinformatics; Biological evolution; Cancer; Cancer genetics; Carcinoma - metabolism; Clostridium difficile; Coevolution; Damage localization; Deoxyribonucleic acid; DNA; DNA sequencing; Drosophila; Epidermis - metabolism; Evolution; Evolution & development; Evolution, Molecular; Evolutionary Biology/Animal Genetics; Evolutionary Biology/Bioinformatics; Evolutionary Biology/Evolutionary and Comparative Genetics; Evolutionary Biology/Human Evolution; Genes; Genetic aspects; Genetics and Genomics/Animal Genetics; Genetics and Genomics/Bioinformatics; Genetics and Genomics/Cancer Genetics; Genetics and Genomics/Genetics of Disease; Genetics and Genomics/Genetics of the Immune System; Genetics and Genomics/Population Genetics; Genomes; Heat-Shock Proteins - chemistry; Humans; Hypotheses; Hypothesis testing; Identification methods; Immune response; Immune system; Immunology; Immunology/Innate Immunity; Infections; Innate immunity; Insects; Linkages; Mammals; Membrane Proteins - chemistry; Models, Biological; Molecular biology; Molecular evolution; Molecular Sequence Data; Mucosal immunity; Mutation; Neoplasm Proteins - chemistry; Neoplasms - metabolism; Nucleotide sequence; Oncology/Gastrointestinal Cancers; Oncology/Gynecological Cancers; Open Reading Frames; p53 Protein; Pathogens; Phylogeny; Population genetics; Proteins; Sequence Homology, Amino Acid; Signal transduction; Stress; Stress response; Stresses; Tumor proteins; Tumor Suppressor Protein p53 - metabolism; Viruses; United Kingdom > UK; Scotland; Edinburgh Scotland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0001003

Some cancers are mediated by an interplay between tissue damage, pathogens and localised innate immune responses, but the mechanisms that underlie these linkages are only beginning to be unravelled. Here we identify a strong signature of adaptive evolution on the DNA sequence of the mammalian stress response gene SEP53, a member of the epidermal differentiation complex fused-gene family known for its role in suppressing cancers. The SEP53 gene appears to have been subject to adaptive evolution of a type that is commonly (though not exclusively) associated with coevolutionary arms races. A similar pattern of molecular evolution was not evident in the p53 cancer-suppressing gene. Our data thus raises the possibility that SEP53 is a component of the mucosal/epithelial innate immune response engaged in an ongoing interaction with a pathogen. Although the pathogenic stress mediating adaptive evolution of SEP53 is not known, there are a number of well-known candidates, in particular viruses with established links to carcinoma.