Field of Science

The computer model of USS evolution

Yesterday the postdocs and I spent some time thinking/talking about our computer model project. I have all sorts of assumptions that the postdocs don't, resulting from all the work I did last year on this, so a lot of time is spent discovering these, explaining them (which requires my rethinking them) and then deciding whether they should be kept or discarded for the present work.

I also worked on my draft (outline, really) of the manuscript describing this work, and got in in good enough shape that it could be given to the postdocs. They can use it to get a clearer idea (because in writing) of what I'm thinking, and thus as a framework to see ways our various ideas can be improved.

And I went through the code of some versions of the program from last summer. Programming (for me) is like experimental research in that I mostly have a series of goals, each resulting from rethinking the previous work and results, but do a lot of blundering around. Thus the various versions have different sub-goals and different flaws, some of which I made of and some of which I didn't. And they're in different degrees of completion - some I think I had set aside without finishing making changes...

But luckily I was very conscientious about annotating the code as I wrote it, so every line or group of lines has at least a few words of explanation. On rereading I found the overall structure of the programs (all very similar) to be less complex than I had remembered it. It was easy for me to bracket off the little clusters of commands and label them with what they were accomplishing. The details of how they accomplish it are not so clear, because I've forgotten how many of the commands work, especially the search and replace ones that are the heart of the program.

I think it's a very nice program. Our first big challenge is to get it to run to 'equilibrium'. That is, after enough generations under any specified settings of the mutation rate and DNA uptake probabilities, the simulated DNA sequence should get to a state where its properties are not changing. Because the simulated steps have a component of randomness, there will still be lots of changes from generation to generation, but when averaged over many generations there should be no net change. Our main scientific goal is to characterize the equilibria, and the approach to equilibria, over a wide range of biologically-relevant conditions.

But getting to and recognizing the equilibria is challenging for a couple of reasons. First, because of the randomness, it's not easy to decide on good criteria for recognizing equilibrium. I'll post more on this another time. Second, getting to equilibrium ( or close enough to meet whatever criteria we set) can take a long time, and so we need to modify the model so we can run it on a fast computer 'grid' we have access to.


  1. Does "achieving equilibrium" mean that you are starting with a naive genome (2Mb of random DNA sequence?) that has never seen a USS (thus has ~8 or so?), then start bombarding it with both USS (which modify the genome through recombination) and point mutations (which can arise anywhere)? Then you wait many generations and see whether you achieve a stable rate of change arising only through "background" point mutations and recovery of USSs through recombination after they have mutated to one-offs?

  2. I think I remember you talking about this program before during lab meeting. So by doing this, you can construct an evolutional tree with the bootstrap % right?

  3. I've read over the outline and found it helpful for clarifying our goal and plan of action. I would be interested in talking about your old analytical model too.

    I've spent some time with the code today and plan to do more this weekend. I am now working with the file. I've added in several lines at the beginning so that we can have an error file, instead of errors being printed to the screen.

    Other than that, I've printed all of your blogs concerning this project and plan to read and think about it some more this weekend/early next week. So I am sure I will have plenty of questions!

  4. scmt: Yes, that's a good description of what we're doing. I don't know that I'd describe the equilibrium as "a stable rate of change". Instead it's a stage where the mean number of USS is stable despite generation-to-generation fluctuations. I suspect that the locations of the USS will not be very stable, with some occasionally being lost and new ones arising at different locations.


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