mutation – Jonathan Eisen's Lab

Punctuated equilibrium of my blog … and a look at an old science rap

Well, with my new role in PLoS Biology as Academic Editor in Chief, I had planned to start blogging more about PLoS and PLoS Biology. And I will. However, I am going to have to do a half effort on this for at least a week or two as I have a lovely ailment called trigger finger which is making typing rather awkward. So in lieu of a detailed blog I simply have to make a brief comment on one of the articles in this months issue

The article in which I am interested is a nice primer on mutational meltdown in mammalian mitochondrial genomes by Dave Rand. This is in relation to a paper by Stewart et al. in this issue. But enough about science. For those who do not know, Dave Rand published what I believe was the first rap in a scientific article. In an article in Genetics he presented a rap about repeat induced point mutation (something known as RIPPING). This RAP about RIPPING I think was presented at the Evolution meeting in Berkeley (I think I was at the talk where he did the RAP but I am not sure — I could have, like Andy Pettite, misremembered the whole thing).

And well, here it is:

Yo! you’ve got my DNA and you think it is a-RIPping,
Your dog is so excited her saliva is a-dripping,
She seems to think the polymerase is doing some a-skipping,
But then again, you never know, she might just be a-quipping.
Are you sure induction by repeats did make it happen?
If it’s just associated, why not call it RAPpin’?
What motifs are necessary to keep the strands a-snappin’?
I don’t know and I don’t care, but something did some zappin’.

What can Justin Timerblake tell us about evolution?

I read with fascination an article in the New York Times magazine this weekend on Pop Culture entitled “Is Justin Timberlake a Product of Cumulative Advantage?” No, I was not fascinated by the Timerlake part. But what was interesting was Duncan Watt’s argument that it is very difficult to predict the success or failure of entities in pop culture. He presented a model that is summarized as “The cumulative advantage:”

The reason is that when people tend to like what other people like, differences in popularity are subject to what is called “cumulative advantage,” or the “rich get richer” effect. This means that if one object happens to be slightly more popular than another at just the right point, it will tend to become more popular still

He then described an experiment they performed that was published in Science last year where

more than 14,000 participants registered at our Web site, Music Lab (www.musiclab.columbia.edu), and were asked to listen to, rate and, if they chose, download songs by bands they had never heard of. Some of the participants saw only the names of the songs and bands, while others also saw how many times the songs had been downloaded by previous participants. This second group — in what we called the “social influence” condition — was further split into eight parallel “worlds” such that participants could see the prior downloads of people only in their own world. We didn’t manipulate any of these rankings — all the artists in all the worlds started out identically, with zero downloads — but because the different worlds were kept separate, they subsequently evolved independently of one another.

They used this set up to test among two different possibilities.

First, if people know what they like regardless of what they think other people like, the most successful songs should draw about the same amount of the total market share in both the independent and social-influence conditions — that is, hits shouldn’t be any bigger just because the people downloading them know what other people downloaded. And second, the very same songs — the “best” ones — should become hits in all social-influence worlds. What we found, however, was exactly the opposite. In all the social-influence worlds, the most popular songs were much more popular (and the least popular songs were less popular) than in the independent condition. At the same time, however, the particular songs that became hits were different in different worlds, just as cumulative-advantage theory would predict. Introducing social influence into human decision making, in other words, didn’t just make the hits bigger; it also made them more unpredictable.

Why you may ask am I so fascinated by this? Well, what he described is mathematically and conceptually identical to Luria and Delbruck’s fluctuation test (see my earlier blog about L & D), where they were testing the origin of mutants. Luria and Delbruck designed a test where they grew E. coli from the same starting point in different culture tubes. Then they exposed these tubes to selective pressures. If the number of mutants in the tubes were basically the same, this would mean that the mutants arose in response to the selection. If the number of mutants were vastly different (somehting they called a jackpot pattern) this would mean the mutants arose in the growth of the bacteria in the tubes prior to selection.

In the entertainment experiment, the different music “worlds” are the equivalent to the different test tubes. And the preferences of people are the equivalent of the selection. Their result in the music experiment was the jackpot pattern – the same thing seen by Luria and Delbruck. For Luria and Delbruck this meant selection did not guide mutation. For the music, this means the personal preference for the music has less influence than the random history of which music was picked early on.

So – thank you Justin for a modern lesson in evolution.

Classic papers in genetics and evolution that are available in Pubmed Central – Paper 1 – Luria and Delbruck on the origin of mutations

I am starting a new series here —- finding and writing about classic papers in Evolution and Genetics and Molecular Biology that are available for free in Pubmed Central. And though plenty of classic papers are not avilable, a good collection of them are.

My first selection is Luria and Delbrück’s paper from 1943 on the origin of mutations. This papers is near and dear to my heart in many ways and I still remember looking it up for the first time when I was an undergraduate. I was taking a class from Jennifer Doudna on the origin of life, and we had to write a paper as part of the class. In the class we had discussed a new paper by John Cairns and colleagues that revisitid the origin of mutations question. Cairns et al. result suggested to them at least that bacteria could pick and choose the mutations they needed for increased fitness in a particular situation (suggestive of so-called Lamarckian evolution to them). I was fascinated by this work (so much so, that it became the topic of my grad. school application essays and the topic of my first two years of PhD research in Phil Hanawalt’s Lab). So I chose to write a paper on the origin of mutations.

Obviously, to write such a paper I had to go to Luria and Delbrück’s work since they were the first to experimentally test the question of how much mutations pre-existed selection and how much they arose after selection. I stillremember sifting through the old journals in the library at Harvard to find this and turning the pages in teh dust covered volume to read it.

Luria and Delbrück chose as their experimental system resistance to bacteriaphage and their model organism, Escherichia coli. In their paper first the describe the theoretical underpinning of their wor. In their theory they come up with a way to do an experiment to test whether mutations pre-exist selection or arise in response to it – something now generally known as a fluctuation test. Basically the idea is simple. Take a particular form of the bacteria. Innoculate multiple test tubes with a small amount and let each test tube grow up to a dense culture. Then expose bacteria from each tube to the selective pressure. If the mutations pre-exist selection then there should be big differences between the replicate test tubes in the number of mutants since in some the mutation would arise early in the growth of the culture and in some they would arise late (this is known as a jackpot distribution). If the mutations arise after selection then each tube should have somewhat similar numbers (with some variation around a mean).

And when they did the experiments the results followed very closely the jackpot model. They stated:

We consider the above results as proof that in our case the resistance to virus is due to a heritable change of the bacterial cell which occurs independently of the action of the virus. It remains to be seen whether or not this is the general rule. There is reason to suspect that the mechanism is more complex in cases where the resistant culture develops only several days after lysis of the sensitive bacteria.

And thus they showed that mutations unequivocally pre-exist selection. Now, it turns out that their experiment had a flaw – since they were using a lethal selection (phage) the system did not really allow for a long period of time for the mutations after selection to arise (when your dead it is hard to generate mutations). The Cairns experiment (and Ryan’s before him) showed that some unusual results occurred if you used a non lethal selection. So one cannot really use Luria and Delbrück’s experiment to disprove the possibility that mutations arise after selection. Nevertheless, their proof that mutations can exist before selection was a fundamental discovery. And their methods were used throughout bacterial genetics for years (to this day in fact). For more detail see Access Excellence page about Luria and Delbruck.

This is such a fundmentally important paper, and it is great that this paper is available, free to all, in Pubmed Central. See below:

Mutations of Bacteria from Virus Sensitivity to Virus Resistance.

Luria SE, Delbrück M.

Genetics. 1943 Nov; 28(6): 491-511.
PMCID: 1209226
| Abstract | PDF-1.3M |