@Mercer -
Your point is well-taken. It is true that I haven’t been heavy in the research of this lately. To give a bit of history, this paper that I’m presenting is actually itself almost ten years old. I wrote the paper shortly after doing a poster presentation on the topic. The road to publication has been long. When I first wrote it, I tried to publish it at an ordinary journal, and had mixed reviews (one very positive, one very negative). I wasn’t very familiar with the publication process at the time, so I wasn’t really sure where to go or what to do or who to send it to. Anyway, I first sent it to BIO-Complexity in 2012, where it was rejected because at the time they were only doing experimental papers. A few years later, they had opened it up to more types of papers, and I submitted it again, and it was rejected because I had some mathematics errors. A few years later, I went back through and did a detailed cleanup of the math and got a mathematician friend, Asatur Khurshudyan (who had previously coauthored a mathematics paper with me on changes to the second derivative) to help me out (he’s mentioned in the acknowledgements). I submitted this, and the mathematician had some initial pushback, but finally got it through.
All that to say, there are indeed older references, but that is due to the publication history. Would it be great if I had the time to keep up with everything? Sure, but I also have a day job, a teaching job, and two secondary writing jobs, so it is true that I don’t always have time to keep up with everything. However, a cursory review of the paper you cited seemed to indicate that it was a AID site prediction study, not an experimental study (actually it looked like a combined study, but it was hard to tell from a brief review how much was predicted vs. demonstrated). The problem with prediction techniques is that it assumes that the cell doesn’t have compensation machinery as well (in fact, it also assumes that SMH is the only valid usage of AID). But nonetheless, I will certainly grant that you have a broader knowledge of the SMH literature than I do.
Anyway, if you are correct, then that would not argue against my main idea (that you can measure active information and this is a good way to measure it), but only the application (that I have correctly applied the idea that I stated). If there winds up being less active information in SMH than I think there is because I measured it too casually, so be it. It’s not the main idea, just a way to understand how simplifications of the concept can work.
Another thing to notice, though, is that “selection” is being used in an equivocal way here. If the organism targets a cell for destruction because it doesn’t meet the standards, that is not “selection” in the Darwinian sense, but more similar to targeted mutation. If the cell simply falls apart because it is broken, then that is indeed selection in the Darwinian sense. But, if the organism is terminating the cell because it detects that the cell is operating outside its boundaries, that’s not Darwinian selection. Is it active information? Probably not, because the organism did indeed “try” at that point. Anyway, it is an interesting discussion, and I’m happy to say that you know more about the details than I do.
Again, my goal, as stated in the paper and in this thread, is to supply a mechanism for testing the question of whether or not organisms contain information about likely targets of evolution. I am not invested in any particular outcome for any particular process, especially as the present paper is concerned. I’m only concerned with whether the testing mechanism, if wielded by the appropriate person, would perform as indicated. Matheson, despite thinking the paper isn’t worthwhile, did in fact think that the testing mechanism would in fact perform as indicated. I don’t really care if Matheson likes me or the paper, or thinks that me or the paper is worth the time of day. I am interested in the fact that he thinks that the paper does what it says it will do.
I will say, however, that, in my (admittedly limited) reading, I have several times found that lack of targeting has occurred due to identifiable mutations which make off-target sites more likely to occur. This is more well-documented with the RAG enzymes during V(D)J recombination, but I have found papers on it. I imagine we will find more, but, as Matheson points out, my suppositions aren’t science.
@Dan_Eastwood -
I think you are still thinking of the paper in the same way that Swamidass started out thinking. You say,
This is a complete misunderstanding of what I am doing. I am not testing whether or not mutations follow a uniform probability. I am testing whether or not mutations, as they occur in nature, are more successful or less successful (or even) than they would be if they did follow a uniform probability. This is the important point. Let’s say there is a strong bias of mutations. But, let’s say that this bias generally doesn’t favor the organism’s results. This would be negative active information, because it would be pointing away from success. The reason why a uniform distribution of mutations is the right thing to test against is because we have no reason for thinking that mutations should or should not be biased towards function. Using the amount of function that a uniform distribution gives tells us where the “zero point” is - the expected value of an arbitrary mutation. Mutational biases may be more helpful or more harmful than arbitrary mutations. That’s what active information seeks to find out.
When someone says that “mutation is random with respect to function”, they are saying (or at least most people are understanding) that the outcome of the mutation is no more or less functional than any other arbitrary transformation on the genome. Therefore, this measures this question and assigns a value to it. Note that the measurement is useful (as mentioned previously) even if this was not the original question intended by the statement “mutation is random with respect to function”. But, in addition to its uses in detecting possible, previously-unknown mutational mechanisms, it also serves the function of forcing people to be more quantitative about statements like this
Anyway, this has been fun, and I appreciate everyone’s thoughtful contributions. Unless anyone has specific questions for me, I’m happy to leave y’all with the last word.