sfs
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If your chart is based on the Kimura paper you cited, then your description of it is wrong. Kiimura's paper does not describe the real distribution of mutation effects in the human population -- which still isn't known, and wasn't remotely known when Kimura wrote his paper -- but a theoretical distribution that has some nice properties for his model. Here's where he introduces the distribution in the paper:
In other words, he simply assumed the shape of the distribution.
His curve is wrong, and massively so, for human mutations. First, note that ~95% of the genome seems to have no function, so that fraction of mutation will be completely neutral. Of the remaining mutations, a much larger fraction than the curve would suggest are highly deleterious, enough so to be removed by natural selection.
Consider just the coding regions of genes, which are the parts of the genome that are the best understood. They are about 1.5% of the genome, or 50 million base pairs. Single base subsitutions (easily the most common mutations) within coding regions either change the amino acid that is coded for (nonsynonymous) or don't (synonymous). Roughly two-thirds of substitutions are nonsynonymous. Of these, approximately 75% are deleterious enough to be removed by selection. (This can be seen both in within-species studies (Nature Genetics 22:231 (1999)) and in comparing humans and chimpanzees (Nature 437:69 (2005).) That means that fully half of all mutations are to the left of Kimura's box, which isn't at all consistent with his curve.
Of the remaining mutations, some undoubtedly are mildly deleterious, and accumulate freely in the genomes of organisms like humans. For many of them, the selective disadvantage is tiny, and the correct response is, "So what?". Being slightly less fit relative to a perfect member of your species isn't very important to evolution, when the perfect member doesn't exist; you only compete against real organisms, not ideal ones.
There is an intermediate range of mildly deleterious mutations that are more interesting, however. These have a selective disadvantage too small to be eliminated by selection in the human population, but large enough that the effects become significant as more and more mutations pile up. For example, synonymous mutations don't change the protein, but for highly expressed genes they may slow production of the protein down by a bit, since the translation machinary is forced to use less common transfer RNAs. So if you start with optimal production, repeated synonymous mutations may gradually make the expression level of the protein lower and lower, leading to a less (healthy, happy, bouncy, whatever) organism.
Does this spell disaster (i.e. extinction) for the species? Well, no. As the species drifts towards lower and lower fitness as a result of changes at that gene, the opportunity for beneficial mutations increases; the farther you are from perfect fitness, the more likely it is that a change will be good for you. In this case, a mutation that increases transcription of the gene will have a substantial benefit, and will be favored by natural selection.
For a real, finite population, then, what happens is that the species is never perfectly adapted. Instead, it is constantly drifting away from the adaptive peak, and occasionally getting bumped back toward it from selectively advantageous mutations. For really small populations, the species may be in trouble, unable to adapt fast enough to overcome the accumulation of mildly deleterious alleles. That's one reason that small populations are in danger of extinction.
I don't know what you mean, but it sounds wrong. Natural selection operates at the level of the organism.
The curve goes to infinity at 0, which might be a reason to take it with a grain of salt.
No, evolutionary theorists don't do that at all. They know quite well that deleterious alleles within the box are still deleterious, which is why they're referred to as "mildly deleterious alleles", not "completely neutral".
You are misunderstanding something fundamental here. The rate of beneficial mutations depends strongly on the environment (something Kimura actually points out in this paper). It has to. The beneficial mutation rate for an organism that is perfectly adapted to its current environment must be zero, since "perfectly adapted" means it can't get any better. Change the environment, and suddenly there are ways the organism could be improved, and so the beneficial mutation rate will go up.
There was a paper within the last few weeks in Science that reported a very nice series of experiments with bacteria (E. coli), measuring the beneficial mutation rate in an environment where the bacterium was not well adapted. They measured a beneficial mutation rate of the greater than 1 per 100,000 bacteria (i.e. 10^-5/genome replication). The total mutation rate for E. coli is only about 1 mutation per 400 replications, so the beneficial mutation rate in this environment was on the order of 1% of all mutations, which is enormous.
Of course mutations can cause a loss of information, by most definitions of information. What you need to show is that mutations must cause a loss of information.
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