Tuesday, 29 January 2008

Wonders of Molecular Biology: DNA Packaging

Inspired by biophysics lecture by ANK

What is tennis ball having to do with biology?

There are many amazing facts you will encounter when you start looking at looking at life at the very small scale. This article is the first in a series of articles I am writing about the wonders of molecular biology.

As I briefly mentioned in my previous biology post, the cell is controlled through a pathway of information flow from DNA to RNA to protein. The first step in this flow is called transcription, the creation of RNA from DNA template. For transcription to happen, the molecular machinery responsible for transcription (the RNA polymerase[1]) needs to have physical access to the appropriate DNA region (the gene) to be transcribed.

It might not be immediately obvious why this is such a big problem until you compare the scale of things. In eukaryotic[2] cells, for example in human cells, DNA is localized only in the cell nucleus[3]. The nucleus in human cell is about 6μm in diameter (this is a millionth of a meter). On the other hand, the human genome[4] contains 3.2 billion base pair[5] of DNA, which translates to about 2 meter of fully extended length in diploid[6] cell. Now imagine squeezing something 2 meter in length into a millionth of a meter. This is equivalent to squeezing a 40km fishing line into a tennis ball!

[Figure of cell with nucleus, chromosome, DNA. Taken from Wikipedia]

So how is this compaction problem addressed in the cell? This is by no mean an answered problem in biology. What we know is that DNA is compacted in a structured hierarchy: short segment of DNA is bound to form “beads-on-a-string” chromatin, chromatins are packed in increasingly complex structure to form the chromosome. In human there are two copies of 24 different chromosomes[7] in one cell.

[Reproduced from Molecular Biology of the Cell – 4th edition]

Compaction is one problem. Another problem which is less well understood is about access. This highly compacted DNA is still needed for the daily function of the cell. It is not like going to self-storage company to dump all of your clutters and forget about them. The cell needs constant replenishing of proteins to maintain its normal functions as well as to respond to the changing environment. Going back to our tennis ball analogy, this is similar to having to pull out specific bits of the heavily tangled fishing line while still keeping them compact inside the tennis ball. There are different theories about this which I would not go in any details. In short there are two classes of thoughts:
  1. The passive access, where access is available through dynamic unwinding of the compacting structure. This is the same as having the fishing line wiggles around inside the tennis ball and at certain time, a specific region of the line will be exposed for access.
  2. The active access. In this scenario, the proteins play an active role by driving the nucleosome to open up certain region of DNA.
It is likely that a mixture of both approaches is used in the cell.

I think I should stop here for now. I hope that this post give you a flavour for the interesting world of molecular biology. If you want to read more about this, check out some molecular biology texbooks. Molecular Biology of the Cell is a recommended read for its clear explanation and illustration.

PS: This post is written to laymen. I have to simplify a lot of things. So biologist, please take with a (or many if you are a salty person) pinch of salt.

[1] polymerase: “-ase” usually indicates protein that functions as an enzyme. An enzyme is something that speeds up a chemical reaction without being converted into the final product. In this case polymerase means enzyme that catalyzes the formation of long chain of polymer. The polymerase drives the formation of this polymer, but at the end of the reaction, the polymerase is still at the same condition as when it starts and is not converted in the reaction.
[2] eukaryotic: A class of organism that is characterized by the presence of nucleus inside the cell.
[3] cell nuclei (or –us when plural): An enveloped region inside the cell that contains the DNA. The nuclei is separated from the rest of the cell by a lipid membrane.
[4] genome: the complete genetic information of an organism.
[5] base pair: The DNA is formed of nucleotides (coded as A, T, G, C), each of which forms favourable chemical interaction with a specific partner (A with T, G with C). A base pair (one pair of interacting nucleotides) is a commonly used unit for measuring the length of DNA.
[6] diploid: Having two copies of every chromosome. Most of our cells are diploid, except of our germ cells (sperms and eggs) which are haploid (carrying only one copy of the chromosome).
[7] chromosome: An organizational unit of tightly packed DNA. Chromosome is formed from one piece of very long DNA.


Rand said...


Are you in science... biological sciences?

I'm a research technician in the field of proteomics (chiefly, that makes me a Mass Spectrometrist for protein samples), at the National Research Council of Canada. I actually have my name on at least three scientific journals (my boss is a very generous with authorship).

That would really be something... both Bible street evangelists AND scientists...

Take care,


Rand said...

Ah! Got it!

Jessica's husband is in science I take it (I just read the first "biology post).

Wow... God bless you, my friend. Christian and in science, we're not very numerous...


Jessica said...

Ah.. Rand! I didn't know you are a scientist as well. I know, many Christian sort of avoiding this field, which I think a bad move. We need more influential and commited christian working as scientist to convince other that science and God is not contradicting each other. Anyway, I am an embedded software engineer and my husband is the one who pursue PhD in BioPhysics in Oxford University, I understand nothing about his entries.
God bless u too!

Rand said...

"... I understand nothing about his entries."

My wife and I will be celebrating 10 years of marriage tomorrow, and she still has no idea what exactly I do for a living (she just calls it "science-stuff")