Abstract
BackgroundGene promoters have guided evolution processes for millions of years. It seems that they were the main engine responsible for the integration of different mutations favorable for the environmental conditions. In cooperation with different transcription factors and other biochemical components, these regulatory regions dictate the synthesis frequency of RNA molecules. Predominantly in the last decade, it has become clear that nuclear organization impacts upon gene regulation. To fully understand the connections between Homo sapiens chromosomes and their gene promoters, we analyzed 1200 promoter sequences using our Kappa Index of Coincidence method.ResultsIn order to measure the structural similarity of gene promoters, we used two-dimensional image-based patterns obtained through Kappa Index of Coincidence (Kappa IC) and (C+G)% values. The center of weight of each promoter pattern indicated a structure similarity between promoters of each chromosome. Furthermore, the proximity of chromosomes seems to be in accordance to the structural similarity of their gene promoters. The arrangement of chromosomes according to Kappa IC values of promoters, shows a striking symmetry between the chromosome length and the structure of promoters located on them. High Kappa IC and (C+G)% values of gene promoters were also directly associated with the most frequent genetic diseases. Taking into consideration these observations, a general hypothesis for the evolutionary dynamics of the genome has been proposed. In this hypothesis, heterochromatin and euchromatin domains exchange DNA sequences according to a difference in the rate of Slipped Strand Mispairing and point mutations.ConclusionsIn this paper we showed that gene promoters appear to be specific to each chromosome. Furthermore, the proximity between chromosomes seems to be in accordance to the structural similarity of their gene promoters. Our findings are based on comprehensive data from Transcriptional Regulatory Element Database and a new computer model whose core is using Kappa index of coincidence.
Highlights
Gene promoters have guided evolution processes for millions of years
In the third analysis we examined the distribution of Kappa IC values against the number of genetic diseases associated with each chromosome
Our results suggest that promoters located on chromosomes which contain regions frequently included in heterochromatin, seem to exhibit only average to low Kappa Index of Coincidence values (Figure 2B), which further suggests that among other roles, heterochromatin is acting as a shield for the inner core against point mutations originating from outside the nucleus
Summary
Gene promoters have guided evolution processes for millions of years. It seems that they were the main engine responsible for the integration of different mutations favorable for the environmental conditions. Euchromatin domains which are never stored as facultative heterochromatin are usually under active transcription and contain housekeeping genes, otherwise crucial for basic cell functions [15]. Genes embedded inside facultative heterochromatin can transit to and from euchromatin, depending on different functions that the cell needs to perform, in certain time intervals or under the action of certain external stimuli. Polycomb-group proteins and other biochemical mechanisms reshape chromatin depending on the cell type, allowing a favorable positioning of these genes inside euchromatin domain [32]. In terminally differentiated somatic cells, Hox genes are permanently silenced by their inclusion inside heterochromatin domain. In female morphogenesis an X chromosome is silenced through its condensation inside facultative heterochromatin [33,34,35] (the Barr body), while the active X chromosome is included in euchromatin domain.
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