Molecular Biology and Evolution, Vol 16, 194-207, Copyright © 1999 by Society for Molecular Biology and Evolution
DL Crawford, JA Segal and JL Barnett
Many molecular studies describe how components of the proximal promoter
affect transcriptional processes. However, these studies do not account for
the likely effects of distant enhancers or chromatin structure, and thus it
is difficult to conclude that the sequence variation in proximal promoters
acts to modulate transcription in the natural context of the whole genome.
This problem, the biological importance of proximal promoter sequence
variation, can be addressed using a combination of molecular and
evolutionary analyses. Provided here are molecular and evolutionary
analyses of the variation in promoter function and sequence within and
between populations of Fundulus heteroclitus for the lactate
dehydrogenase-B (Ldh-B) proximal promoter. Approximately one third of the
Ldh-B proximal promoter contains interspersed regions that are functionally
important: (1) they bind transcription factors in vivo, (2) they effect a
change in transcription as assayed by transient transfection into two
different fish cell lines, and (3) they bind purified transcription factors
in vitro. Evolutionary analyses that compare sequence variation in these
functional regions versus the nonfunctional regions indicate that the
changes in the Ldh-B proximal promoter sequences are due to directional
selection. Thus, the Ldh-B proximal promoter sequence variations that
affect transcriptional processes constitute a phenotypic change that is
subject to natural selection, suggesting that proximal promoter sequence
variation affects transcription in the natural context of the whole genome.
ORIGINAL ARTICLE
Evolutionary analysis of TATA-less proximal promoter function
Division of Molecular Biology and Biochemistry, University of Missouri, Kansas City 64110, USA. crawd@cctr.umkc.edu
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