Garte: The Meaning of "Random" Mutation

[T_aquaticus]

@sygarte

That does seem like a good analogy, but it actually misses the point, I believe. Because the bets are not random, meaning people who place bets are not equally likely to bet on a 2 and a 7, They know the odds, and will bet on 7 whenever possible (and they do).

The same applies to the environment with fitness being non-random.

@sygarte

As for mutations, there actually are some connections between what the organism needs, and the mutations that do happen. Josh on another thread agreed that “All these mutational mechanism are biased towards changes that are more likely to increase fitness.”

What he meant (I think) is that mutations are biased towards conservative amino acid changes, that is changes towards amino acids that are more like the original amino acid. However, there is no specificity with respect to the environment or the specific genetic locus. It is very much like 7 being more common than 2 or 12 in craps.

@sygarte

And as you pointed out above, we also know that expressed genes are more susceptible to mutation, resulting in a higher number of beneficial mutations (also deleterious ones, but they don’t count) in those genes, which can appear as if the organism favors mutation sites that provide a benefit. This is probably the explanation of the results of John Cairns in 1988, later confirmed by Susan Rosenberg and others.

As you state, this only increases the mutation rate in genes, and those mutations occur whether they are neutral, beneficial, or detrimental. As an analogy, this is like poor people buying more lottery tickets than rich people. Even though this trend exists the lottery is still random.

@sygarte

So, like Perry, I am still perplexed by the meaning of random when applied to mutations. Clearly cells dont decide to mutate specific genes in response to stress, but there do seem to be many mechanisms in place (including error prone repair, which I dont think has been mentioned yet) that tend to bias the results of mutations in a positive direction. I dont see how that process could be labelled random, unless the definition being used is different from the statistical one I have in mind.

A scenario I would consider non-random would be a membrane bound protein that sensed antibiotics and then triggered other enzymes to make a specific mutation in a specific gene to produce antibiotic resistance.