Biotechnology and Molecular Biology Reviews Vol. 2(3), pp. 086-096, August 2007
ISSN 1538-2273 © 2007 Academic Journals

Standard Review
 

Analysis and manipulation of the genome dynamic structure

Valentina Tosato* and Carlo V. Bruschi

Yeast Molecular Genetics Laboratory, International Centre for Genetic Engineering and Biotechnology, AREA Science Park – W, Padriciano 99, IT-34012 Trieste, Italy.

*Corresponding author. E-mail: tosato@icgeb.org. Tel: +39-040-375-7318. Fax: +39-040-375-7343.

Accepted 7 May, 2007

After the genomic era, during which DNA sequencing revealed genes and the post-genomic era, in which their functional analysis was implemented, the notion of a dynamic genome has become convincing. Indeed, since the early days of DNA transposition, new evidence has accumulated indicating a high level of intrinsic structural plasticity characterizing the genome. An ensemble of gross chromosomal rearrangements has been reported, together with their biological effects, some of which correlate to major cellular pathologies such as cancer. From microorganisms to human cells, the convoluted architecture of chromosomes has gained relevance not only from a descriptive point of view, but also as a potential multi-layered storage mechanism of genetic information. The higher-order structure of DNA, including hairpin turns, bending and curvature, as well as precise chromatin topology, could provide the metadata on super-information needed to explain the low number of inferred mammalian genes, perhaps conferring new scientific dignity to the infamous „junk DNA“. In this view, genome dynamics, including the clustering of essential genes and the synteny of others, appears as the paramount cellular response to varying environmental conditions, resulting in massive differential regulation of gene expression. A deeper understanding of the various orders of complexity of genomic DNA structure has allowed the design of more sophisticated biochemical and biophysical tools for its analysis and manipulation, which, in turn, has yielded a better knowledge of the genome itself. This creative cycle is providing new generations of diagnostics and intelligent drugs of pharmacogenomic origin that exploit the ever changing, yet stable, genome dynamic structure.

Key words: Genome dynamics, secondary DNA structure, gross chromosomal rearrangements