The Evolution of DNA Regulatory Regions for Proteo-Gamma Bacteria by Interspecies Comparisons

AUTOR(ES)

Rajewsky, Nikolaus

FONTE

Cold Spring Harbor Laboratory Press

RESUMO

The comparison of homologous noncoding DNA for organisms a suitable evolutionary distance apart is a powerful tool for the identification of cis regulatory elements for transcription and translation and for the study of how they assemble into functional modules. We have fit the three parameters of an affine global probabilistic alignment algorithm to establish the background mutation rate of noncoding seqeunce between E. coli and a series of gamma proteobacteria ranging from Salmonella to Vibrio. The lower bound we find to the neutral mutation rate is sufficiently high, even for Salmonella, that most of the conservation of noncoding sequence is indicative of selective pressures rather than of insufficient time to evolve. We then use a local version of the alignment algorithm combined with our inferred background mutation rate to assign a significance to the degree of local sequence conservation between orthologous genes, and thereby deduce a probability profile for the upstream regulatory region of all E. coli protein-coding genes. We recover 75%–85% (depending on significance level) of all regulatory sites from a standard compilation for E. coli, and 66%–85% of sigma sites.

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