Adaptive evolution of a stress response protein.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Little
Tom J
TJ
Institute of Evolutionary Biology, School of Biology, University of Edinburgh, Edinburgh, United Kingdom. tlittle1@staffmail.ed.ac.uk
Nelson
Lenny
L
Hupp
Ted
T
D000595:Amino Acid Sequence; D000818:Animals; D002277:Carcinoma / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism; D019143:Evolution, Molecular; D006360:Heat-Shock Proteins / Q000737:chemistry*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry*; D009369:Neoplasms / Q000378:metabolism*; D016366:Open Reading Frames; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C418764:CRNN protein, human; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53