Sunday, August 21, 2011

How Does Something Get into a Textbook?

A recent paper in Molecular Cell involved the study of nucleosome assembly in vitro (Torigoe et al. 2011). The authors were looking for intermediate stages in the assembly of nucleosome after DNA replication. Here's the abstract of their paper ...
Chromatin assembly involves the combined action of histone chaperones and ATP-dependent motor proteins. Here, we investigate the mechanism of nucleosome assembly with a purified chromatin assembly system containing the histone chaperone NAP1 and the ATP-dependent motor protein ACF. These studies revealed the rapid formation of a stable nonnucleosomal histone-DNA intermediate that is converted into canonical nucleosomes by ACF. The histone-DNA intermediate does not supercoil DNA like a canonical nucleosome, but has a nucleosome-like appearance by atomic force microscopy. This intermediate contains all four core histones, lacks NAP1, and is formed by the initial deposition of histones H3-H4. Conversion of the intermediate into histone H1-containing chromatin results in increased resistance to micrococcal nuclease digestion. These findings suggest that the histone-DNA intermediate corresponds to nascent nucleosome-like structures, such as those observed at DNA replication forks. Related complexes might be formed during other chromatin-directed processes such as transcription, DNA repair, and histone exchange.
Interesting but hardly Earth-shattering. More work needs to be done to confirm this result and see if it's significant in vivo. At least that's what you would think if you just looked at the paper.

You get a very different perspective if you read the press release from the University of California at San Diego: Biologists' Discovery May Force Revision of Biology Textbooks: Novel Chromatin Particle Halfway Between DNA and a Nucleosome.1
Basic biology textbooks may need a bit of revising now that biologists at UC San Diego have discovered a never-before-noticed component of our basic genetic material.

According to the textbooks, chromatin, the natural state of DNA in the cell, is made up of nucleosomes. And nucleosomes are the basic repeating unit of chromatin.
That's correct. All the textbooks have a diagram similar to the one shown here from my textbook. It shows the organization of nucleosome core particles and the completed nucleosome on DNA.

What the new result shows is that there's an intermediate stage where the core particle is bound to DNA but the DNA isn't wrapped around the core particle. That's not a big surprise and it's not going to make it into most textbooks, even if it's true.
"This novel particle was found as a precursor to a nucleosome," said James Kadonaga, a professor of biology at UC San Diego who headed the research team and calls the particle a "pre-nucleosome." "These findings suggest that it is necessary to reconsider what chromatin is. The pre-nucleosome is likely to be an important player in how our genetic material is duplicated and used."

The biologists say that while the pre-nucleosome may look something like a nucleosome under the microscope, biochemical tests have shown that it is in reality halfway between DNA and a nucleosome.

These pre-nucleosomes, the researchers say, are converted into nucleosomes by a motor protein that uses the energy molecule ATP.

"The discovery of pre-nucleosomes suggests that much of chromatin, which has been generally presumed to consist only of nucleosomes, may be a mixture of nucleosomes and pre-nucleosomes," said Kadonaga. "So, this discovery may be the beginning of a revolution in our understanding of what chromatin is."
This is mostly hype and none of this speculation is found in the actual paper. Unfortunately, this sort of press release has become the norm and that's got to stop.

This work isn't even close to making into the textbooks for a number of reasons. The most obvious is that it needs to be confirmed. Textbook writers do not immediately put new findings into their books because we've been burned too many times. But there's another reason why this ain't gonna make it—it's not important enough.

Textbooks are not encyclopedias. They will only contain information that undergraduates need to know in order to understand the basic concepts and principles in the field. I know that every scientist thinks his or her most recent discovery is Nobel Prize work and I'm sure they would like every biochemistry undergraduate to know about it. At some point a textbook author has to decide what's really important and, unfortunately, those choices mean that 99.99% of everything that's published in a given year doesn't make the cut.

It can't be any other way.

1. It even seemed important enough for Richard Biologists' Discovery May Force Revision of Biology Textbooks: Novel Chromatin Particle Halfway Between DNA and a Nucleosome.


  1. As a fledgling textbook writer, I'm curious about your decisions about what goes into a new edition and what doesn't. I find that adding in relatively recent research is a good way to breathe new life into a subject. Rather than stick with examples of evolution form the 1950s, I can look at all sorts of recent studies that can integrate natural history with genomics, etc., because scientists have many more tools at hand. I think this strategy can make a subject more interesting to students, because they can see how the science is rolling along even today--it didn't stop in 1950.

    On the other hand, I have written about really new papers that reviewers later flagged as being less impressive than they might appear. So I am finding it a tricky balancing act. What are your criteria?

  2. Good Question!

    I focus on fundamental principles and concepts. That's the stuff students need to know. If a recently published result enhances one of those concepts, or provides an interesting example, then I'll consider putting it into my book.

    Since my book is an introductory biochemistry textbook I'm not really interested in the latest results at the front line of the field. It's very rare that anything published in the recent literature will change the good old-fashioned basic concepts that students need to know.

    But here's the problem. The instructors who use the textbook are often researchers and they would dearly love to think that beginning undergraduates will be as excited as they are about the latest paper in Science or Nature.

    That's just not true. In order to understand and appreciate those papers the students will have to learn a lot of basic stuff first. We need to make that basic stuff as interesting—and as accurate—as possible and we're not doing our students any favors by sacrificing the basics for the glamor.

    It's very frustrating because some intructors won't use my book because we don't have a whole chapter on "signal transduction" or "systems biology" or "cancer", or "bioinformatics."

  3. I appreciate a mix of older classic examples in my textbooks, and some newer spins to try and give students a notion of what the frontier looks like.

    When it comes to something more involved and specialized, I think that is best approached based on the individual instructors territory. I believe students benefit, by some of the excitement, interest, and detail that you can deliver when talking about your field. The trick of course is that you can't really put that into the textbook for other people outside your field.

  4. not curious or interested in the evolution of chromatin? be critical of the mainstream encrusted tenured bioideology, it's only there to guide imagination, so some silly idea as a precursor to chromatin can open a door that suggests how far we need to go