Research On The Evolution Of Upstream Stimulatory Factors

Upstream stimulating factors (USF), belonged to multifunctional transcription factor family, are ubiquitously expressed in eukaryote. It contains the two members of USF1 and USF2. USF is also a kind of alternatively spliced gene, for example, USF2 may create many splicing variants by alternative splicing, such as USF2⊿1, USF2⊿2, USF2⊿3 and USF2⊿4 in rat. These variants can interact with each other to control the expression of the genes containing E-box regulatory elements. USF proteins possess the typical structure of the conserved basic-Helix-Loop-Helix- Leucine-Zipper, and are involved in cell proliferation, glucid-lipid metabolism and UV-activated pigmentation as well as the synthase of prostaglandin in granulosa cells. Moreover, the abnormity of USF function may lead to several diseases, such as dyslipidemias and diabetic glomerulosclerosis. It therefore is great significance to further study the function of USF, and in this article, the molecular evolution of the protein family was systematical investigated using both exon-intron structure and protein sequences. Comparative analysis of protein sequences and gene structures revealed that usf1 and usf2 are resultants of gene duplication. The position and phase of introns of usf1 and usf2 seemed to imply that independent intronic deletion or insertion may have occurred in separate lineages, and the protein sequences and exon-intron structure of usf genes in vertebrates are highly identical, in contrast with the high diversity seen in between invertebrates, which implied that vertebrate usf genes may have undergone very sharp convergence in evolution. Comparative analysis also found that alternative splicing patterns of usf family genes are highly conserved. Point mutation and additional sequence insertion in introns might have given rise to new isoforms. In addition, prediction for leucine zipper had indicated that this structural domain may be newly inserted into usf genes. Above results seem to have delineated the evolutionary dynamics of usf genes in eukaryotes.