Eukaryotic genomes may exhibit up to 10 generic classes of gene promoters

The main function of gene promoters appears to be the integration of different gene products in their biological pathways in order to maintain homeostasis. Generally, promoters have been classified in two major classes, namely TATA and CpG. Nevertheless, many genes using the same combinatorial formation of transcription factors have different gene expression patterns. Accordingly, we tried to ask ourselves some fundamental questions: Why certain genes have an overall predisposition for higher gene expression levels than others ?. What causes such a predisposition ?. Is there a structural relationship of these sequences in different tissues ?. Is there a strong phylogenetic relationship between promoters of closely related species ?.

In order to gain valuable insights into different promoter regions, we obtained a series of image-based patterns which allowed us to identify 10 generic classes of promoters. A comprehensive analysis was undertaken for promoter sequences from Arabidopsis thaliana, Drosophila melanogaster, Homo sapiens and Oryza sativa, and a more extensive analysis of tissue-specific promoters in humans. We observed a clear preference for these species to use certain classes of promoters for specific biological processes. Moreover, in humans, we found that different tissues use distinct classes of promoters, reflecting an emerging promoter network. Depending on the tissue type, comparisons made between these classes of promoters reveal a complementarity between their patterns whereas some other classes of promoters have been observed to occur in competition. Furthermore, we also noticed the existence of some transitional states between these classes of promoters that may explain certain evolutionary mechanisms, which suggest a possible predisposition for specific levels of gene expression and perhaps for a different number of factors responsible for triggering gene expression. Our conclusions are based on comprehensive data from three different databases and a new computer model whose core is using Kappa index of coincidence.

To fully understand the connections between gene promoters and gene expression, we analyzed thousands of promoter sequences using our Kappa Index of Coincidence method and a specialized Optical Character Recognition (OCR) neural network. Under our criteria, 10 classes of promoters were detected. In addition, the existence of “transitional” promoters suggests that there is an evolutionary weighted continuum between classes, depending perhaps upon changes in their gene products.

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Recently, at European Congress of Diabetes (EASD) which took place in Berlin between 30 september – 5 october 2012, a Poster (number 280) presentation was related to the gene promoters associated with type I and type II diabetes. Using kappa index of coincidence and the content of %CG, the pattern of promoters was different in type I phenotype versus type II phenotype diabetes. The result was largely commented by the participants and has been proposed that this new method for approaching the genome to be extended for analysis also of gene sequences in order to compare them with the pattern of promoters.

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