How DNA is like a Magnet

Now that we have piles and piles of widely available genome sequence, one of our main tasks as biologists is to figure out how to read what’s in there. Protein-coding sequences have long been relatively easy to read, ever since the genetic code was worked out. Non-coding regulatory sequences – enhancers and promoters – are much more difficult to interpret, obviously. Usually our first task is to identify the individual binding sites for gene-regulating proteins in these sequences. But then what? Well, most people stop there, happy to have identified the necessary parts of the gene regulating machinery, but many of us are interested in learning the underlying logic by which this machinery operates – we want to learn the grammar of regulatory DNA. The question is, how does a particular combination of regulatory binding sites give rise to a particular pattern of gene expression? In my biased opinion, this the real secret of life – how your cells read information in your DNA in order to turn on the right genes at the right place in the right time.

So, how do we read non-coding, regulatory DNA? One way that has proven very useful is take an approach from the 1920’s that was developed to understand the physics of magnets. No, I’m not talking about the pseudoscience of biomagents; I’m talking about Ising models. Continue reading “How DNA is like a Magnet”

Scientific Award FAIL

Larry Moran reports that John Mattick, author of the infamous dog-ass plot, has won some genomics-related award that I have never heard of.

Moran has the sorry details:

I’m pretty sure that there’s no more than a handful of biochemists/molecular biologists who believe Mattick. They know that lots of noncoding DNA has a function—a fact that’s been in the textbooks for almost fifty years—but they do not believe that most of our genome encodes functional regulatory RNAs. It’s simply untrue that Mattick has proved his hypothesis over the past 18 years. Just the opposite has happened.

He quotes the press release:

The Award Reviewing Committee commented that Professor Mattick’s “work on long non-coding RNA has dramatically changed our concept of 95% of our genome”

Uh, no. Not true. Continue reading “Scientific Award FAIL”

Scientists scooped by evolution

It turns out that your classic experimental trick to mimic protein phosphorylation by mutating serines and threonines to aspartate or glutamate at phosphorylation sites was not first discovered by humans. Pearlman, Serber and Ferrell argue that many phosphorylation sites in proteins evolved from negatively charged amino acid residues, which means that phosphorylation evolved to mimic the effects of glutamate and aspartate. This, of course, occurred long before human scientists discovered in 1987 that you could replace phosphorlated serines and threonines with negatively charged amino acids and still get a functional protein.

“A Mechanism for the Evolution of Phosphorylation Sites”, Samuel M. Pearlman, Zach Serber, James E. Ferrell Jr., Cell Volume 147, Issue 4, 11 November 2011, Pages 934–946 Continue reading “Scientists scooped by evolution”

Single cell gene expression linkfest

Gene regulation is an old field, but gene regulation at the single cell level is a whole new ball of wax. Some of us in the lab are trying to get up to speed in this field, and I need to pick out five good papers for consideration.

The place to begin is with this great review, and then work through the references:

Central dogma at the single-molecule level in living cells, Gene-Wei Li and X. Sunney Xie, Nature 475, 308–315 (21 July 2011)

Picking selectively, I ended up with the list below, and unfortunately I need to somehow narrow this down to five… and preferably all five won’t be from Sunney Xie’s group. Any suggestions?

Quantifying E. coli Proteome and Transcriptome with Single-Molecule Sensitivity in Single Cells, Yuichi Taniguchi, Paul J. Choi, Gene-Wei Li, Huiyi Chen, Mohan Babu, Jeremy Hearn, Andrew Emili and X. Sunney Xie, Science 30 July 2010: Vol. 329 no. 5991 pp. 533-538 Continue reading “Single cell gene expression linkfest”

If I read the words ’emergent properties’ one more time today…

… in a developmental biology paper, I’m going to have to start breaking things.

This is almost as bad as referring to the collection of genomic data as the “canonical ensemble” approach. (FYI, Wikipedia: “canonical ensemble”)

I would like to know, when is a response to a morphogen gradient not considered an emergent property?