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Comment by sevenless | Hacker News Reader

I find it fascinating we still don't really know how life works. I have a hunch we are going to find the large scale 3D structure of the chromosome is a big deal, and these genes regulate it. There aren't many good tools to study chromosome structure and it's quite possible there's a whole layer of information we've missed so far.

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Actually there are new approaches to study exactly that, and they are developing rapidly, cf: https://en.wikipedia.org/wiki/Chromosome_conformation_captur... Basically, this problem, along with a long list of other applications is being attacked by deep sequencing. The way it works is that you apply a treatment to DNA that 'glues' 3D contacts in place and covers the glued segment, apply restriction enzymes to cut out what's not covered by glue, get rid of the glue, sequence all that's left, and then map the remaining sequenced fragments to the reference genome. The output is the relative tendency of different regions to come into contact with each other.

> The 3-D organization of the genome can also be analyzed via eigendecomposition of the contact matrix.

Love it when linear algebra pops up in unexpected places!

There is a significant branch of microbiology that studies the 3D structure of chromosomes. Epigenetics is the study of how gene expression (rather than composition) affects a phenotype. There is a strong influence of structure, telomeres, centromeres, and expression modifiers that work at a physical level. It will certainly be a major component of functional life. It took decades after genetics were established for the scientific community to accept epigenetics as a valid influence and avenue of study (due to both a lack of methods to accurately study these aspects of an organism and scientific inertia).

edit: pedantics.

that's not biochemistry- it's structural biology. Biochemistry focuses almost entirely on reducible components in isolation.

That's actually already an area of active study.

See http://www.sciencedirect.com/science/article/pii/S1534580708...

You mean like this:

"Second layer of information in DNA confirmed"

http://phys.org/news/2016-06-layer-dna.html

That's a theoretical study by physicists; it's a bit of a misleading headline, and anyway it's for eukaryotes, not bacteria, which are much smaller.

Thanks for putting that into context.

>it's quite possible there's a whole layer of information we've missed so far

Can you expand on this comment? What would such a layer look like? Have we missed layers before and then found them?

The whole story of molecular biology has been discovering layers of control and information: DNA, genes, gene regulation, RNA, RNA splicing, protein structure and regulation, protein interactions, micro-RNAs... and it's usually been limited by the tools that scientists could bring to bear. Possibly there's another control layer in charge of the long range structure of the chromosome. Being wet, squishy and fragile, it's hard to study.

This was my thought as well. Likely the remaining genes represent some kind of meta-process, effecting and/or controlling how the genes we understand are expressed.

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