Functional analysis of human and chimpanzee promoters

Background: It has long been argued that changes in gene expression may provide an additional
and crucial perspective on the evolutionary differences between humans and chimpanzees. To
investigate how often expression differences seen in tissues are caused by sequence differences in
the proximal promoters, we tested the expression activity in cultured cells of human and
chimpanzee promoters from genes that differ in mRNA expression between human and
chimpanzee tissues.
Results: Twelve promoters for which the corresponding gene had been shown to be differentially
expressed between humans and chimpanzees in liver or brain were tested. Seven showed a
significant difference in activity between the human promoter and the orthologous chimpanzee
promoter in at least one of the two cell lines used. However, only three of them showed a
difference in the same direction as in the tissues.
Conclusion: Differences in proximal promoter activity are likely to be common between humans
and chimpanzees, but are not linked in a simple fashion to gene-expression levels in tissues. This
suggests that several genetic differences between humans and chimpanzees might be responsible
for a single expression difference and thus that relevant expression differences between humans
and chimpanzees will be difficult to predict from cell culture experiments or DNA sequences.