What is the typical rate of spontaneous mutations?
Rates of spontaneous mutation seem to be determined by evolutionary balances between the deleterious consequences of many mutations and the additional energy and time required to further reduce mutation rates. Bacteria, Archae, and Eukaryotic microbes produce about one mutation per 300 chromosome replications. For E. coli this works out to be between 10-6 and 10-7 mutations per gene per generation, however it is important to note that there are certain "hot spots" or "cold spots" for spontaneous mutations. (A "hot spot" is a site that has a higher rate of mutations than predicted from a normal distribution, and a "cold spot" is a site with a lower rate of mutations than predicted from a normal distribution.) Higher eukaryotes have the same rate of spontaneous mutation, so that rates per sexual generation are about one mutation per gamete (close to the maximum compatible with life). RNA viruses have much higher mutation rates -- about one mutation per genome per chromosome replication --
and even small increases in their mutation rates are lethal.
DNA Mutation Rates and Evolution
This Poisson approximation shows that out of 10,000 offspring, only 2,202 of them would have the same or less than the original number of detrimental mutations of the parent population. This leaves 7,798 with more detrimental mutations than the parent population.51 Of course, in order to maintain a steady state population of 5,000, natural selection must cull out 5,000 of these 10,000 offspring before they are able to reproduce. Given a preference, those with more detrimental mutations will be less fit by a certain degree and will be removed from the population before those that are more fit (less detrimental mutations). Given strong selection pressure, the second generation might be made up of ~2,200 more fit individuals and only ~2,800 less fit individuals with the overall average showing a decline as compared with the original parent generation. If selection pressure is strong, so that the majority of those with more than 7 detrimental mutations are removed from the population, the next generation will only have about 1,100 mating couples as compared to 2,500 in the original generation. With a reproductive rate of 4 per couple, only 4,400 offspring will be produced as compared to 10,000 originally. In order to keep up with this loss, the reproductive rate must be increased or the population will head toward extinction. In fact, given a detrimental mutation rate of Ud = 3 in a sexually reproducing population, the average number of offspring needed to keep up would be around 20 per breeding couple (2eUd/2). While this is about half that required for an asexual population (2eUd), it is still quite significant.
In this light, consider that more recent estimates suggest that the deleterious mutation rate is even higher. "Extrapolations from studies of humans and Drosophila (Mukai, 1979; Kondroshov, 1988; Crow, 1993) suggest that Ud > 5 is feasible." 49 However, the number of required offspring needed to compensate for a detrimental mutation rate of Ud = 5 would soar to 148 per female per generation! And, this is not the worst of it. Recent genetic studies have shown that much of what was once thought of as "junk DNA" is actually functional ( Link ). In fact, these recent studies suggest that the total amount of functional DNA in the human genome is not actually 2-3% as previously thought, but is upwards of 85-90% ( Link ). Consider also that what were once thought to be neutral mutations are now being discovered to be functional mutations governed by natural selection. In a 2007 paper published in the Indian Journal of Human Genetics, author Clyde Winters claims to have made a very interesting discovery.
It is often assumed that selection plays a limited role in the mtDNA control region. . . However, there is a selective constraint on mutation frequencies of an mtDNA site. Some of the East African transitions . . . are the most rapidly occurring nucleotide substitutions in the human mitochondrial genome. These transitions are often referred too as "hotspots." These hot spots of mutational activity suggest that positive selection influences mutation rates and not neutral selection which, theoretically, would manifest parallel mutations.53
Of course, this is not the only region in the human genome that was once thought to be limited to neutral mutations alone. Much of the genome is now known to be subject to differential selection.
So what. What does this matter? It matters to this particular problem because the actual detrimental mutation rate would be a significantly greater percentage of the total number of mutations experienced by the genome in each generation. As noted above, the total number of mutations per offspring per generation is at least 175. If the functional genome percentage was actually 50% (instead of just 2%), the likely detrimental mutation rate (Ud) would be well over 30 instead of the usual estimates of ~3 noted above. This would increase the reproductive rate needed to avoid genomic decay from ~20 offspring per woman per generation to well over 10 trillion offspring per woman per generation - obviously an impossible hurdle to overcome.
In short, the best available evidence overwhelmingly supports the theory that the human genome is in decay. The various forms of "positive epistasis" (see illustration by Rice below) 49 do not solve this problem.