> "An interesting question is: What determines the mutation rate in a living organism," Al-Hashimi said. "From there, we can begin to understand the specific conditions or environmental stressors that can elevate errors."
Which leads to an interesting point: higher mutation ratios lead to more diversity and faster evolution/adaptation, but also lead to a higher % of cells/embryos failing due to destructive mutations (such as cancer).
Similarly, lower mutation rates increase stability and decrease cell/embryo mortality rates, but at the cost of adaptability and evolution.
With that in mind, you'd expect that fast-changing environments would select for genes that increase mutation rates, leading to faster evolution but with higher mortality rates, and stable environments would select genes that decrease mutation rates, resulting in larger populations and lower mortality rates.
It is amazing to think that even the rate of mutations is probably an evolutionary response to the environment.
>With that in mind, you'd expect that fast-changing environments would select for genes that increase mutation rates
I've seen the opposite in a bioreactor (about the most stable environment you can have). Variants slowly emerged and outcompeted each other until a variant emerged with a DNA repair pathway deleted. The spawns of that variant quickly out-competed the old ones and from then on there were ~10 dominant variants at any given time instead of the previous 1-3.
Because the environment was so stable, the genes did not need to "remember" previous states of the environment and were free to optimize for the current state. The way to do this is to increase the mutation rate, as you potentially delete old genes that are no longer necessary and create new genes that are right for the moment.
Edit: I suppose this points out a difference between "fast-changing" in a single direction and "fast-changing" that repeats states, such as seasonal changes.
>It is amazing to think that even the rate of mutations is probably an evolutionary response to the environment.
Now consider that mutation is not a single "rate" across the genome. Instead, mutations are targeted to specific regions! Some genome sequences have mutation rates of 10^-3, compared to 10^-9 for most of the genome.
So, when considering mutation in relation to evolution, examine the genes with high mutation rates, especially in their regulatory regions. If fast-changing environmental FACTORS can influence evolution, then hypermutability may be advantageous in genes that interact with these factors. By targeting mutations to specific genomic regions, organisms can "bet-hedge" with specific traits, increasing the probability of survival during extreme environmental shifts.
Think about growth rates in relation to boom-bust food cycles, or neural development in relation to dynamic social conditions. What evolutionary strategies would be optimal for rapidly changing environmental factors? Increasing mutation rates genome-wide is not the answer, as you point out it leads to problems with viability. Thankfully, mutation rates are local and traits are bet-hedged against variable environments.
What a wonderfully variable species we are! We adapted to different environments worldwide! And it only took tens-of-thousands of years?! Amazing :)
It might be just about the mutation rate being "higher" or "lower" but also about the volume of reproduction. Even with higher or lower mutation rates, failed embryos/offspring can be offset by higher levels of reproduction. Think how mice reproduce huge numbers of offspring versus humans and many other mammals supporting only 1 at a time.
I would also add that volume of reproduction and lifespan of an organism also plays a role. Even if your mutation rate is "low" but you reproduce a lot and have a short lifespan (think like fruit flies) then you could offset slow mutation because your generational mutations are happening quickly.
In short, mutation rate can't be the only factor that might be selected for given environments that might be experiencing huge amounts of change.
Mutation rates can vary by orders of magnitude from tissue to tissue, with germline tissue apparently being the lowest.[1]
There is no reason to think that the rates important for adaptability/evolution have anything to do with those involving cancer and organ failure of non-gonadic tissue.
It is described as Evolution Strategies (proposed in the 1970s) which adapt individual mutation rates depending on the search landscape at hand. Unfortunately, biologist will learn about in a few decades at best.
> certain C/C++ variables can shape-shift for a thousandth of a second, transiently morphing into alternative states that can allow the program to crash or produce an incorrect result
> certain DNA bases can shape-shift for a thousandth of a second, transiently morphing into alternative states that can allow the replication machinery to incorporate the wrong base pairs into its double helix
I find this fascinating. I had always assumed that it was the shapeshifting of the polymerase that caused replication errors. Clearly that's not the whole story!
We already know the polymerase error rate is the dominant factor - Comparison between various different polymerase error rates shows differences in error rates span across a 6-7 orders of magnitude.
> certain DNA bases can shape-shift for a thousandth of a second, transiently morphing into alternative states that can allow the replication machinery to incorporate the wrong base pairs into its double helix
As I understand it, its already been mathematically proven that the efficiency of a utility function declines with the search space, and there can be no global optimum when the search space is infinite. When there is no global optimum it becomes more and more important to have a novelty function that can at least maximize the number of future possible local equilibriums, from the current equilibrium.
The search space of "Every possible life form over 4.5 billion years" is very large, so you would expect there to be a large reward for the right novelty function. And this appears to offer proof of such a mechanism.
> Such mismatches, though rare, could serve as the basis of genetic changes that drive evolution and diseases, including cancer.
The evolution part caught my attention. So we are generating some random changes that can lead to evolution (not that all evolution is good or bad, it's just different from the previous version).
And chemical processes are reprodutible, i.e., given the same conditions, you get the same the result... but in a broader sense, DNA has some unstable, changing configuration, where the molecules are constantly reshaping and can generate different combinations.
Seems that it's not easy to recreate life from chemicals elements alone.
This is just another chemical process, tautomers of nucleic acid bases are well known. Other chemical processes are just as random, but you almost always look at an ensemble of molecules where everything is averaged already.
Which leads to an interesting point: higher mutation ratios lead to more diversity and faster evolution/adaptation, but also lead to a higher % of cells/embryos failing due to destructive mutations (such as cancer).
Similarly, lower mutation rates increase stability and decrease cell/embryo mortality rates, but at the cost of adaptability and evolution.
With that in mind, you'd expect that fast-changing environments would select for genes that increase mutation rates, leading to faster evolution but with higher mortality rates, and stable environments would select genes that decrease mutation rates, resulting in larger populations and lower mortality rates.
It is amazing to think that even the rate of mutations is probably an evolutionary response to the environment.