A organização do DNA é fractal, mas os autores não mencionaram a evolução

Science 9 October 2009:
Vol. 326. no. 5950, pp. 289 - 293
DOI: 10.1126/science.1181369

Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome

Erez Lieberman-Aiden,1,2,3,4,* Nynke L. van Berkum,5,* Louise Williams,1 Maxim Imakaev,2 Tobias Ragoczy,6,7 Agnes Telling,6,7 Ido Amit,1 Bryan R. Lajoie,5 Peter J. Sabo,8 Michael O. Dorschner,8 Richard Sandstrom,8 Bradley Bernstein,1,9 M. A. Bender,10 Mark Groudine,6,7 Andreas Gnirke,1 John Stamatoyannopoulos,8 Leonid A. Mirny,2,11 Eric S. Lander,1,12,13, Job Dekker5,

We describe Hi-C, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. We constructed spatial proximity maps of the human genome with Hi-C at a resolution of 1 megabase. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.

1 Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), MA 02139, USA.

2 Division of Health Sciences and Technology, MIT, Cambridge, MA 02139, USA.

3 Program for Evolutionary Dynamics, Department of Organismic and Evolutionary Biology, Department of Mathematics, Harvard University, Cambridge, MA 02138, USA.

4 Department of Applied Mathematics, Harvard University, Cambridge, MA 02138, USA.

5 Program in Gene Function and Expression and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.

6 Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

7 Department of Radiation Oncology, University of Washington School of Medicine, Seattle, WA 98195, USA.

8 Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.

9 Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.

10 Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.

11 Department of Physics, MIT, Cambridge, MA 02139, USA.

12 Department of Biology, MIT, Cambridge, MA 02139, USA.

13 Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.

* These authors contributed equally to this work.

To whom correspondence should be addressed. E-mail: lander@broadinstitute.org (E.S.L.); job.dekker@umassmed.edu (J.D.)

+++++

EXCERPT/EXCERTO:

Various authors have proposed that chromosomal regions can be modeled as an “equilibrium globule”: a compact, densely knotted configuration originally used to describe a polymer in a poor solvent at equilibrium.... Grosberg et al. proposed an alternative model, theorizing that polymers, including interphase DNA, can self-organize into a long-lived, nonequilibrium conformation that they described as a “fractal globule”. This highly compact state is formed by an unentangled polymer when it crumples into a series of small globules in a "beads-on-a-string" configuration. These beads serve as monomers in subsequent rounds of spontaneous crumpling until only a single globule-of-globules-of-globules remains. The resulting structure resembles a Peano curve, a continuous fractal trajectory that densely fills 3D space without crossing itself. Fractal globules are an attractive structure for chromatin segments because they lack knots and would facilitate unfolding and refolding, for example, during gene activation, gene repression, or the cell cycle. In a fractal globule, contiguous regions of the genome tend to form spatial sectors whose size corresponds to the length of the original region (Fig. 4C). In contrast, an equilibrium globule is highly knotted and lacks such sectors; instead, linear and spatial positions are largely decorrelated after, at most, a few megabases (Fig. 4C). The fractal globule has not previously been observed.

+++++

NOTA IMPERTINENTE DESTE BLOGGER:

Eu não me lembro o nome do cientista eminente, mas acho que foi Crick, que afirmou ser o DNA um acidente congelado. O que vemos aqui é um impressionante sistema de armazenamento de informação complexa especificada que os autores não souberam explicar evolutivamente: não há menção de evolução na pesquisa deles! Por quê???

+++++

Professores, pesquisadores e alunos de universidades públicas e privadas com acesso ao site CAPES/Periódicos podem ler gratuitamente ese artigo da Science e de várias publicações científicas.