Promoters and transcription factors - Human Gene Evolution - page 253

cases, element function (measured in terms of influence on transcription) is
directly proportional to the probability that a specific site is bound by the tran-
scription factor protein. It follows that the same function can be achieved with a
strong binding site and a small amount of protein as with a weak binding site and
a large amount of protein. The extent of selective pressure on the DNA sequence
is therefore likely to be determined by a combination of the cellular abundance of
the protein, the functional activity of the protein and the initial binding strength
of the DNA-protein interaction (Berg, 1992). Transcription factor binding may
however also be influenced by the number of binding sites available on the pro-
moter (Section 5.1.11). Thus, the pituitary-specific growth hormone ( GH1 ;
17q22-q24) gene of humans and rats contains two binding sites for the transcrip-
tion factor Pit-1 whereas four such sequences occur in the promoter of the homol-
ogous Gh1 gene of Oncorhynchus mykiss , the rainbow trout (Argenton et al ., 1993).
Rat Pit-1 has been shown to be capable of binding to three regions of the trout
gene promoter thereby driving expression of a downstream reporter gene
(Argenton et al ., 1993).
5.2.9 Exon shuffling in the evolution of transcription factors
Transcription factors are sometimes encoded by genes that are evolutionarily
unrelated yet share the same type of DNA-binding domain. Such genes may have
arisen by exon shuffling (Chapter 3, section 3.6), the process by which functional
domains encoded by one or more exons have been dispersed to a variety of differ-
ent proteins. That some DNA-binding domains are encoded by several exons
implies that these exons must have been shuffled together as a single block.
Matsuo et al . (1994) have suggested that the presence of short unconserved introns
with different types of splice junction within the mammalian Oct-2 ( POU2F2 ;
chromosome 19) gene may have served to prevent recombination between the
exons comprising the conserved POU domain without inhibiting the shuffling of
this domain in its entirety between different transcription factor-encoding genes
during evolution.
The divergence of the mammalian T-box family of transcription factors, which
began before the separation of the vertebrate, arthropod and nematode lineages,
has occurred both by the insertion or deletion of specific introns, or by intron slid-
ing (Chapter 3, section 3.4) leading to variations in exon length (Wattler et al .,
1998).
References
Adey N.B., Schichman S.A., Graham D.K., Peterson S.N., Edgell M.H., Hutchison C.A. (1994a)
Rodent L1 evolution has been driven by a single dominant lineage that has repeatedly acquired
new transcriptional regulatory sequences. Mol. Biol. Evol . 11 : 778-789.
Adey N.B., Tollefsbol T.O., Sparks A.B., Edgell M.H., Hutchison C.A. (1994b) Molecular
resurrection of an extinct ancestral promoter for mouse L1. Proc. Natl. Acad. Sci. USA 91 :
1569-1573.
Adler A.J., Danielsen M., Robins D.M. (1992) Androgen-specific gene activation via a consensus
glucocorticoid response element is determined by interaction with nonreceptor factors. Proc. Natl.
Acad. Sci. USA 89 : 11 660-11 663.