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Chromosome organisation explained by using a physics model

March 19, 2014 09:49 pm | Updated May 19, 2016 09:54 am IST

Gene-density dependent positioning of chromosomes has been explained.

It is a significant trend that present day advancements in computational techniques have made possible interdisciplinary studies that lend a completely different perspective to problems in biology and medicine. A case in point is a recent work published in the open-access journal Nucleic Acids Research (January 22) in which physics principles have been used to explain the gene-density dependent arrangement of chromosomes within the nucleus.

For a long time it has been known that chromosomes organize themselves within the nucleus such that those chromosomes with a higher gene density are found at the centre of the nucleus and those with less gene-density are found near the edges. There has been much speculation on why this occurs. Nirmalendu Ganai, Surajit Sengupta and Gautam Menon explain this organisation based on a simulation in which they make use of a discretised Langevin equation.

According to their results, this density-dependent radial segregation of chromosomes arises as a consequence of non-equilibrium activity across chromosomes. Non-equilibrium processes are very common in day-to-day life. For example, the way our body maintains its temperature at a constant value despite changes in the external temperature. Such non-equilibrium activity is associated with an increase in energy locally and the molecule ATP found in the cell can supply the energy needed for such processes. For instance, when an ATP molecule breaks up, it releases energy which is of the order of 20 K T, where K T is the equilibrium value.

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By invoking a model in which the inhomogeneous distribution of ATP in chromatin gives rise to non-equilibrium activity, the researchers show that such a density dependent arrangement, or organisation, of the chromosomes emerges naturally.

They compare the predictions of their model with known data on distribution functions for chromosomes 12, 18, 19 and 20 in the relatively spherical human lymphocyte nuclei and find reasonable agreement.

When asked to comment on this, Prof. Ramakrishna Ramaswamy, an expert in computational biology remarked that the model was very interesting especially as it underlined the importance of interdisciplinary work in the solution of biological problems…

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It would be interesting to see what predictions it would make for diverse organisms [with different number of chromosomes] and if these could be validated by experiments.

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