Beneficial Mutations and Protein Activity

[Phydeaux]

I have been searching the internet for a while now and I will continue to do so, but I thought I would ask if anyone here knows anything about or knows of papers about protein activity and it's relation to fitness. I am curious if a significant percentage of mutations increase fitness by reducing protein activity rather than by increasing protein activity. If this is the case, I assume it could have some consequences in the evolution of complex diseases. So yeah, just curious if anyone happens to know. Thank you!

[JackBean]

I'd say this: it's more probably to decrease the activity, but more beneficial would be in many cases (especially with metabolic enzymes) the increase of activity. In the case of some regulating proteins it will depend on what and how they regulate

[kolean]

I do not know if this will help, but there are some papers on caloric restrictions that increase longevity of an organism (with analogy to the Sirtuin proteins and resveratrol) that may include restrictions on protein and its metabolism. It will not be a mutation (that I know of), but a decrease in protein activity.

[MrMistery]

kolean, what did you mean about that? Animals on CR have increased metabolism...

[kolean]

How so? And which animal are we talking about?
http://en.wikipedia.org/wiki/Calorie_restriction

[MrMistery]

pretty much all animals studied. See here a review from nature http://www.ayurveda-florida.com/Researc ... fespan.pdf

The whole reason why people started looking for CR mimmetics was the observation that respiration increases in CR, which meant that the classic "less ROS, less damage" paradigm was wrong. Subsequently David Sinclair found resveratrol, the Sir2 activator. The rest, as they say, is history

[Phydeaux]

The best I could find was an article which gave sickle-cell anemia as an example. I am a little surprised none has done a study on the percentage of mutations which are biochemically deleterious, but selectively advantageous considering the amount of research put into slightly deleterious mutations and "hitchhiking." I suppose beneficial mutations are so rare we simply do not have enough information on them yet.