Man Mark over at Good Math, Bad Math got an advanced copy of Behes latest, 'The Edge of Evolution.' (Foiled by D-list blogging again-- Deniers didnt send me an advanced copy of Blondies 'Science Outsold'. I even asked!)
Now, Behe has always aggravated me, as I first became aware of his existence when I was taking introductory immunology... and I found I could refute his 'arguments' regarding the immune systems. "That dude isnt right" I said to myself at the time.
Ive tried to ignore him as best as I could since then. Honestly, I thought it was a little funny that he went after the bacteriologists with the damn flagellum and the immunologists with "Immune system cant evolve blah blah", but I never thought he be silly enough to go after something I research. I mean Im sure he reads my blog daily and knows hed be snarkified by a chick half his age if he tried to touch stuff I do.
*giggle*
GM/BM-- Anyway, the new book is based on what comes down to a mathematical argument - a mathematical argument that I've specifically refuted on this blog numerous times. I'm not mentioning that because I expect Behe to read GM/BM and consider it as a serious source for his research...
Okay, so I cant claim 'D-list blogger help help Im being repressed' this time. I guess Behe doesnt read much of anything, if Marks summary of his latest book is accurate.
Ouch. I dont talk about my research directly a whole lot here (except for pretty pictures, of course), but like I put in my blurb, I study the evolution of HIV within patients and within populations. Fitness and fitness landscapes are vital to my research. And if Mark has summarized Behes claims properly-- Im kinda peeved *fumes*The basic argument in this chapter is the good old "fitness landscape" argument. And Behe makes the classic mistakes. His entire argument really comes down to the following points:
- Evolution can be modeled in terms of a static, unchanging fitness landscape.
- The fitness landscape is a smooth, surface made up of hills and valleys, where a local minimum or maximum in any dimension is a local minimum or maximum in all dimensions.
- The fitness function mapping from a genome to a point of the fitness landscape is monotonically increasing.
- The fitness function is smoothly continuous, with infinitessimally small changes (single-point base chanages) mapping to infinitessimally small changes in position on the fitness landscape.
No one can have a basic, basic, basic understanding of 'fitness landscapes' and come out thinking those four points are valid. Just watch, Ill explain fitness landscapes to you all right now in the context of HIV, and you will get it! You, even those of you with zero biological training, will be able to refute Professional Creationist Michael Behe! Yay!
Okay, check it out-- think of a graph. On the Y-axis, think of something that contributes to natural selection. For HIV, a good one is T-Cell escape. On the X axis, every point is a potential HIV sequence. EVERY possible HIV sequence. X-axis is real long, but lets pretend it looks like this:
The HIV genome sequences that are 'better' at staying under the radar of T-cells have higher Y-axis values (peaks), and the ones that cant escape very well have lower values (valley).This is a two dimensional graph. Its not really two dimensions. You see, for every contribution to natural selection, you add another dimension. Add a Z-axis to that graph-- escape gp120 antibodies. Add a W-axis-- escape gp41 antibodies. Add how fast Env can get the virus into the infected cell, host nutrition, resistance to Drug 1, resistance to Drug 2, resistance to TRIM5a, resistance to APOBEC, etc etc etc etc etc. Physicists get excited when they find another dimension... but they aint got nothin on HIV fitness landscapes. I dont think you could even quantify how many dimensions there are to that simple 2D graph from above.
So Sequence 1 might be GREAT at escaping T-cells... But it might be awful at controlling TRIM5a. Sequence 2 might be incredibly efficient at infecting cells, but isnt resistant to Norvir. So HIV explores all these possibilities and creates a quasispecies-- instead of points on a graph, like above, when you combine all the possible fitness axes, you get a cloud of maximally fit viruses. NOT optimally fit! Maximally fit, for the given parameters!
This is what you find when you take a blood sample from an infected patient and sequence all the HIV viruses you find-- Most viruses have a very similar sequence, but different enough that you get a cloud, not a single point of identical viruses. Let me amuse you and draw a picture in paint:
But this picture is just a snapshot. One week later, the patient might try a new drug-- the quasispecies will shift. One week later, the patient might transmit a virus to her partner-- quasispecies is presented with an entirely new landscape.
So:
- Fitness landscapes are never static. At least I cant think of a scenario where that would happen. Ever. Someone give an example if you can think of one.
- A peak in one dimension can be a valley in another dimension. This is clearly demonstrated in HIV, where drug resistant viruses obviously have a fitness cost. When you take the patient off the drug, drug resistant HIV is rapidly overtaken by wild-type viruses.
- What is it with Creationists and things always getting 'better'. Right now Im trying to determine if fitness increases/decreases/randomly changes over time in long-term drug naiive HIV patients. For all I know, HIV viruses are decreasing in fitness over time, but increasing in transmissibility. Things dont always go in one direction!
- Dumb, dumb, dumb. One/Two/Three base-pair changes in HIV can tank a sequence from the top of a peak in one dimension (replicative capacity) to the bottom of that dimension, and pop you to the top of the quasispecies in another dimension (drug resistance). One mutation doesnt equal a little better, another mutation equals a little better, another mutation, etc etc etc.












