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Monthly Archives: November 2012
My son and I just listened to a completely engrossing podcast on inheritance from RadioLab. The episode had three stories about different aspects of inheritance and genetic control. The first didn’t capture my interest nearly as much as the next two, so I won’t discuss it here.
The second story proposed and interesting idea of Lamarckean inheritance based on the extraordinary record-keeping of a far-north town in Sweden. In this town, the church kept amazingly detailed records about births, deaths, disease, health and even crop production year to year. When all these data were analyzed, researchers found a strong correlation between the availability of food to men in the village and the health and wellbeing of that man’s children. What might seem unintuitive is that contrary to what you might think, the children of men who suffered through years of starvation when they were ~9-12 years old fared the best. If dad ate well, your health prognosis was poor. If dad ate poorly, your prognosis was better. The effect even seemed to trace down two generations.
The explanation for this was that at this time in a man’s life he is making the cells that will go on to make sperm. Somehow, these cells can receive genetic imprinting that improves the fitness of the offspring.
Let me stop here. I have to say, I think this is entirely unconvincing. I can think of at least one simpler explanation for these data. Further, I can easily imagine how if it was possible to turn on these beneficial changes, evolution would make this the norm rather than the exception.
Consider a population of 100 kids in the target age group during a year of ‘feast.’ 100% of these kids survive and have children. These children have an average lifespan of 50yrs. Given the same group during a year of ‘famine.’ 50% of the kids survive and have children. The children live to an average age of 75 yrs. It appears that the famine during the elder generation improved the fitness of the younger.
But, if we examine the ‘feast’ population again, we might see that they can be broken up into two natural groups, one with a 75yr lifespan (the healthier 50%) and one with a 25yr lifespan (the less healthy). If the famine year selectively kills the weaker kids, then we are simply selecting our way to better health rather than causing it.
Because this is published research I expect that this simple answer was excluded somehow and I hope to find the original work to see that, but the burden of proof rests on the group proposing the more complex explanation.
I’ll see if I can research this a little and write again later, but I wanted to comment right away because I thought that it was an interesting example of how numbers can sometimes lead you astray if you’re not careful.
Oh, and very quickly, the last story…
The last story was about a woman who had adopted a baby girl, Destiny, from a mother who was addicted to drugs and couldn’t support the child. Amazingly, the next three years after that, the same mother gave birth to three more addicted babies that were all adopted by the same family. Because of her frustration about how this woman was so casually bringing more children into the world, one a year, each addicted to heroin et al. at the time of birth, the adoptive mother tried to pass a law to somehow prevent this from happening. When that failed, she worked directly to set up a fund to pay addicted women to undergo surgical sterilization or get long term birth control.
Many saw this as eugenics in action. Personally, I see no convincing connection to eugenics whatsoever based on the fact that the procedure was voluntary and based on a behavior rather than an innate characteristic of the women. Nevertheless, the conversation went places I never expected – mostly because I thought Jad and Robert would not get drawn into such ridiculous speculations and extensions of logic as they did. It was still good listening though.
I highly recommend checking out this episode.
I just completed a survey on the HHMI website that introduced me to some of their resources that I have not yet explored. One that I thought was relevant to our current work is on chromosomes, genes and sex determination. It can be found here.
Follow this link to the BioInteractive Animation Page where you can find the animations of DNA Replication, Transcription and Translation (among others) that we watched and discussed in class.
DNA Replication occurs during the S (Synthesis) phase of cell cycle. The purpose of DNA replication is to create an identical copy of all the DNA in the cell so that, following cell division, both daughter cells will have complete copies of all the information required to build a cell and do all the things the cell does.
Data from several laboratories were elegantly integrated by the work of Watson and Crick to describe the structure of DNA as comprised of two anti-parallel strands bound together by polar (hydrogen) bonds between one purine and one pyrimidine. Including:
1. Erwin Chargaff ‘s observations that
a) DNA was 50% purine (A and G) and 50% Pyrimidine (C and T) and
b) the proportion of A = the proportion of T; the proportion of C = the proportion of G .
2. Rosalind Franklin’s X ray crystallography data that indicated that DNA had a regular, repeating pattern and the molecule was of a specific width.
3. Oswald Avery’s group along with Hershey and Chase established that DNA was the genetic material (therefore making the structure of this molecule of high importance)
4. Knowledge of the distance between molecules engaged in hydrogen bonds.
5. Knowledge of the chemical properties of nucleotide molecules, comprised of hydrophilic deoxyribose sugars and phosphate groups and hydrophobic bases.
Altogether, this information provided enough background for the pair of researchers to arrive at the structure of DNA by engaging in model building.
How this all leads into the mechanism of DNA replication comes down to the following brief statement at the end of Watson and Crick’s Seminal Paper of the structure of DNA:
“It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.”1
What did they mean by this?
“The novel feature of this structure is the manner in which the two chains are held together by the purine and pyrimidine bases…joined together in pairs, a single base from one chain being hydrogen-bonded to a single base from the other chain… [O]nly specific pairs can bond together. These pairs are: adenine…with thymine…, and guanine… with cytosine.”1
So, if the sequence of DNA bases on one strand dictates the sequence of the other, then each of the strands can be used as a template to make another. When this is done with each of the two strands, the result is two identical DNA molecules.
It’s one thing to say that it hasn’t escaped your notice that there is a mechanism for duplicating DNA inherent in its structure, but quite another to say that you know how it works.
This was the question that Matthew Meselson and Franklin Stahl were to solve in 1958.2 They imagined three possibilities:
- A Conservative method of replication – the original DNA splits open and new strands are made based on that information, then the original strands comes back together and the new strands zip together. We conserve both strands of the original copy.
- A Semi-Conservative method of replication – The original DNA splits open and new strands are synthesized to pair with each of the originals, the new DNA then exists with one original strand and one new one.
- A Non-Conservative / Dispersive method of replication – Frankly, I don’t know how this would work, but the result would be two new DNA molecules where bits of each strand of each molecule may be from the original or the new DNA.
How to distinguish between these methods?
Meselson and Stahl devised an experiment that in which they grew the bacteria, E. coli in broth containing DNA made of two different isotopes of Nitrogen. In one broth, let’s call it the ‘light’ broth, they had the light form of DNA with 14N, in the other, ‘heavy’ broth, they had the heavy form of DNA with 15N.
One really is heavier than the other. When they are centrifuged, they will come to rest at different ‘heights’ in the tube.
If the bacteria is grown in broth containing only the heavy DNA, and that DNA is harvested and spun down, you would see a tube like (a) containing a single band of the heavy DNA.
If than bacteria was moved into a new medium containing light DNA, and DNA was allowed to replicate once,
Assuming semi-conservative or dispersive models of development – you would see (b) a single band of intermediate density – because all new DNA would be partly heavy and partly light.
Assuming the conservative model – you would see (c) two distinct bands – one heavy and one light.
So this immediately tests for or against the conservative model.
The actual result was a single intermediate band was found. This eliminates the conservative model of replication, but a second round of replication in the light broth is required to discriminate between those two models.
If the Semi-Conservative model is correct, then the intermediate band would remain, but a new light band would show up (d).
If the Dispersive model is correct, then the intermediate band would inch upwards (become lighter) as more light elements are mixed in randomly within the strands. (e)
What they found was exactly like that pictured in figure d. Further, if the bacteria were allowed to grow for more generations, the ‘light’ band of DNA would become larger as more light DNA is created, while the intermediate band will remain indefinitely.
- Watson. J. D. and Crick F.H.C. “A Structure for Deoxyribose Nucleic Acid” Nature 171, 737-738 (1953).
- Meselson, M. and Stahl, F.W. (1958). “The Replication of DNA in Escherichia coli”. PNAS 44: 671–82.
I forgot… I meant to post a link to an article written in Wired magazine about the EteRNA RNA folding game. It’s an interesting look into how crowdsourcing is beginning to make inroads into science and how clever gamification turns readers into players and puts them to work on deciphering some of the largest data-heavy / problem-solving questions in science. Find that article here, or you can also find the actual magazine at FSCC in the hallway magazine shelf.