Many interesting points here that I wish were backed up by refs.
> "The vast majority of random mutations are harmful."
- You sure they aren't "neutral"?
> "The number of random mutations necessary to produce one lung cell that is better adapted to smoke inhalation is large enough that the entire remainder of the lung already has carcinogenic mutations."
- No, in principle it can be a single point mutation to a promoter that increases affinity for a transcription factor.
> "Sexual reproduction is a mechanism to eliminate harmful mutations without discarding the occasional beneficial mutation."
- So are apotosis and immune surveillance.
> "Humans are now technically capable of identifying a potentially beneficial genetic mutation, and inserting it into an unrelated person's genome."
- No, they aren't. They modify and select cells in a dish, not in a person.
> "It is, however, more likely that the protein result of the mutation will be used to research and develop a pharmaceutical drug or medical procedure that replicates the beneficial effects of the mutation."
- Ok, I am just including this for completeness sake.
> "In short, the probability of you spontaneously developing an adaptive mutation in a non-germline cell is absolutely infinitesimal in comparison to the probability that someone in the last 10000 generations of your ancestors developed such a mutation when producing a sperm or egg cell and passed it along to you."
- You are talking of 10^4 fertilized eggs vs 10^13 cells in my body[1]. I'm not sure how many divisions it is from egg to egg, but it has to be less than the 10^16 supposed to happen during the human life span[2].
Actually I am pretty sure I have read somewhere that the human body probably contains at least one cell that has a mutation at any given bp. I will see if there is time to find it later.
You forgot to include the probability that any given mutation occurs in a cell where such mutation can be observed to produce a beneficial effect.
If one cell in your body mutates such that it might protect your lungs against damage from smoke inhalation, it won't do you any good (nor ill, probably) if that cell is in your toenail matrix.
Nor do all cells in the body divide at a uniform rate.
I would guess that the one type of cell most likely to show an effect from non-germline mutation are the hematopoietic stem cells. They produce all types of blood cell, are self-renewing, and blood cells touch every other part of the body. But they are also only 1/10000th of all myeloid cells. There may be only 10^6 HSCs in one body
Also, 10000 generations of ancestors is not 10^4 fertilized eggs. Most people have two parents. 0 generations of ancestors is 1 fertilized egg. 1 generation is 3. 2 generations is 7. 3 generations is 15. The upper limit on N generations is 2^(N+1)-1 fertilized eggs. For 10000 generations, that is 4e3010 cells. Though the number of individuals in the species eventually limits that number, as multiple inheritance causes some of your ancestors to be counted more than once. The lower limit would be the degenerate case where all 10000 generations were siblings that had at least one son and one daughter, and that is 2e4. So quite a lot of room for variability in there.
> "The vast majority of random mutations are harmful."
- You sure they aren't "neutral"?
> "The number of random mutations necessary to produce one lung cell that is better adapted to smoke inhalation is large enough that the entire remainder of the lung already has carcinogenic mutations."
- No, in principle it can be a single point mutation to a promoter that increases affinity for a transcription factor.
> "Sexual reproduction is a mechanism to eliminate harmful mutations without discarding the occasional beneficial mutation."
- So are apotosis and immune surveillance.
> "Humans are now technically capable of identifying a potentially beneficial genetic mutation, and inserting it into an unrelated person's genome."
- No, they aren't. They modify and select cells in a dish, not in a person.
> "It is, however, more likely that the protein result of the mutation will be used to research and develop a pharmaceutical drug or medical procedure that replicates the beneficial effects of the mutation."
- Ok, I am just including this for completeness sake.
> "In short, the probability of you spontaneously developing an adaptive mutation in a non-germline cell is absolutely infinitesimal in comparison to the probability that someone in the last 10000 generations of your ancestors developed such a mutation when producing a sperm or egg cell and passed it along to you."
- You are talking of 10^4 fertilized eggs vs 10^13 cells in my body[1]. I'm not sure how many divisions it is from egg to egg, but it has to be less than the 10^16 supposed to happen during the human life span[2].
Actually I am pretty sure I have read somewhere that the human body probably contains at least one cell that has a mutation at any given bp. I will see if there is time to find it later.
[1] https://www.ncbi.nlm.nih.gov/pubmed/23829164
[2] http://bionumbers.hms.harvard.edu/bionumber.aspx?id=100379