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Science

Untangling the Human Genome – in 3D! [VIDEO]

3D image of a human genome fractal globule
The human genome represented as a 3D "entity" or fractal globule

The human genome  is comprised of some 3 billion nucleotide bases  (of which there are four, represented by the four letters A, T, C, G) which pair up and comprise our DNA, which in turn is spread out amongst 23 chromosomes located in every cell in our bodies (note: our sex cells have only half the number of chromosomes).

If one were to uncoil the genome from any one cell into one continuous strand of DNA it would measure abut two meters in length (but you couldn’t see it with the naked eye, since the uncoiled DNA is only 5 microns wide!).

One of many mysteries of the Human Genome

With powerful microscopes, scientists have observed that some portions of our genome are tightly compacted into a globular structures that, upon first examination, appear to be rather messy; base pairs of nucleotides on one end of a stretch of DNA can end up right next to nucleotides at the other end. But the exact structure of these “globules”, and their function (if any), has remained a bit of a mystery.

In reality, these globules of genetic data and building material are not so messy, but are in fact arranged in a particular geometric configurations known as fractal globules, a discovery made by Massachusetts Institute of Technology Ph.D. candidate (and Harvard Fellow) Erez Lieberman Aiden.

A new 3D mapping technique fills in gaps in genome science

In an award-winning essay publish today in the journal Science, Aiden details his original mathematical technique for mapping the human genome — a technique that is already helping geneticists and cell biologist understand the nature of the genome — in three dimensions.

Aiden’s new mapping technique addresses a critical gap in our scientific knowledge about the genome; intermediate between the smallest level of our DNA’s double helix and its nucleotide pairings, and the macro-molecular level of our cell’s 23 chromosomes, are long stretches of thousands or millions of base pairs whose particular folding structure may play a crucial role in genome functioning.

Using this new mapping technique, Aiden and colleagues Miriam Huntley and Rob Scharein have been able to expand upon earlier research to figure out which base pairs have coiled up next to each other. This knowledge allowed them to reconstruct the long string of letters (i.e., A, T, C, G) into a 3D “entity”. Their reconstruction is helping scientists see the precise way that genome packing and folding determines which genes are “on” and which are “off”.

Over the past few years, Aiden and colleagues have been analyzing these genetic globules on the order of 1 million base pairs (reflecting that intermediate level of genetic organization noted earlier). Their work has revealed an exquisite organized structure — the fractal globule — that can be uncoiled without becoming tangled.

In a humorous analogy, Aiden refers to these fractal structures in terms that every college student can understand: Ramen noodles, which come in small packages containing 30 meters of noodles, woven together, but untangled.

VIEW the short, 3D animation of the initial unraveling of a fractal globule, created by Aiden:

For more information on Aiden and this imaging technique, check out the original Sci AM article ‘Human Genome Untangled in 3-D’

Top image: (fractal globule of genetic material) Miriam Huntley/Rob Scharein/Erez Lieberman Aiden




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