So this seems to justify the new time, but the paper also warns that this is only true if the variation is "selectively neutral," which I flat out don't believe. So instead of using a mathematical model with a suspect assumption, lets look at Fossil evidence. I found this paper quite interesting - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471373/As noted above, the net sequence divergence between human and chimp APOE genes was estimated as 64.7; the average pairwise sequence difference among human haplotypes in the same genomic region was 2.93. If a constant molecular clock is assumed and the humans-chimpanzee time of divergence is taken as 5 million years BP, the time required to generate the observed variation would be ∼226,000 years.
It has lots of good stuff, but what I found most interesting looking at modern man DNA from fossils in Europe ranging in age between 1,500 and 43,000 years ago (post Neanderthal) to see if there was a temporal pattern to ApoE varients. They came up with the following:
Which had two big surprises
1. The oldest E4 was 8,000 years ago, and most were less than 5,000 years ago. This while E3s went as far back as 24,000 years ago.
2. All except the oldest one were homozygotes - 4/4, 3/3 or 2/2.
Since we know E4 is the oldest variant, it suggests to me a couple of things. First off, there seems to be little mixture of ancient DNA among separate groups, Each group was either all 4 or all 3. E3 likely arose around 40,000 years ago and gave advantage to farming/high carb groups and spread throughout Europe during the next 35,000 years until it was the only one. Around 5,000 years ago, the Yamnaya people from near the Black Sea developed the wheel and used horses. They swept west into Europe, particularly in the North. If you compare the Yamnaya percentage of DNA in different areas of Europe, you will find it very similar to the percentage of E4. https://en.wikipedia.org/wiki/Yamnaya_c ... migrations