Sorry, it took me a little while to go through the Boyko paper. It’s super statistics heavy. What I’m reading from there is that 27.3–29.0% of mutations are neutral, 30-42% are moderately deleterious, all the rest are highly deleterious or lethal. The statistics indicate that 10-20% of mutations have been fixed by positive selection (again assuming a common ancestor with chimpanzees). Deleterious, as you mentioned, specifically means harmful to reproduction. So in this context, diseases like Huntinginton’s, hemophilia, familial ALS, sickle cell, Lynch syndrome would be considered “neutral”. These statistics are mostly derived from Americans of African decent, as the clustered rate of mutation in Americans of European decent was too high to model well.
The Jonsson paper had a similar average rate of mutation of order 10^-8 per base pair as the other paper we looked at, which translates to about 3 per generation.
So what I don’t understand, and maybe you can help me, is that in the extreme case of 20% of mutations being avoided by positive selection, there’s still 7% of mutations with potentially horrific consequences. This is already excluding the over 70% of mutations that decrease reproductive fitness. What evolutionary pressure is there to keep “neutral” genetic diseases from accumulating in a population over time? How can “beneficial” mutations outweigh this burden? Mathematically, it seems to me that macro evolution is impossible. Am I missing something?
Sorry, it took me a little while to go through the Boyko paper. It’s super statistics heavy. What I’m reading from there is that 27.3–29.0% of mutations are neutral, 30-42% are moderately deleterious, all the rest are highly deleterious or lethal. The statistics indicate that 10-20% of mutations have been fixed by positive selection (again assuming a common ancestor with chimpanzees). Deleterious, as you mentioned, specifically means harmful to reproduction. So in this context, diseases like Huntinginton’s, hemophilia, familial ALS, sickle cell, Lynch syndrome would be considered “neutral”. These statistics are mostly derived from Americans of African decent, as the clustered rate of mutation in Americans of European decent was too high to model well.
The Jonsson paper had a similar average rate of mutation of order 10^-8 per base pair as the other paper we looked at, which translates to about 3 per generation.
So what I don’t understand, and maybe you can help me, is that in the extreme case of 20% of mutations being avoided by positive selection, there’s still 7% of mutations with potentially horrific consequences. This is already excluding the over 70% of mutations that decrease reproductive fitness. What evolutionary pressure is there to keep “neutral” genetic diseases from accumulating in a population over time? How can “beneficial” mutations outweigh this burden? Mathematically, it seems to me that macro evolution is impossible. Am I missing something?