Is ApoE4 Neanderthal?

[mike]

In addition to telling me I was E4/E4, 23andMe said I had above average (2+ %) Neanderthal DNA and it got me to thinking. The E4 variant appeared some 220,000 years ago. At that point, Neanderthal had already broken off from modern man and left for Europe. It could be that in Africa at that time, man had discovered how to cook tubers, and the E3 variant came about, allowing man to access carbs year round. Then when man again came out of Africa, they came with the ability to better utilize carbs than the Neanderthal. A new and likely more available food source during harsh winters. A huge advantage.

[NF52]

In addition to telling me I was E4/E4, 23andMe said I had above average (2+ %) Neanderthal DNA and it got me to thinking. The E4 variant appeared some 220,000 years ago. At that point, Neanderthal had already broken off from modern man and left for Europe. It could be that in Africa at that time, man had discovered how to cook tubers, and the E3 variant came about, allowing man to access carbs year round. Then when man again came out of Africa, they came with the ability to better utilize carbs than the Neanderthal. A new and likely more available food source during harsh winters. A huge advantage.

Hi Mike,
I think you were one of the folks whose posts on Friday got lost in the ether when our forum's server company had an inadvertent data deletion. Here's a link to Julie G's explanation if you're interested https://www.apoe4.info/forums/viewtopic.php?f=23&p=59286#p59286. Thank you for taking the time to re-post. I had seen this Friday, and hadn't had a chance to respond. Great question and fascinating topics!

Like you, I have a decent amount of Neanderthal DNA, 313 variants or a little less than 4% of my total DNA. My ApoE 3/3 husband has 315 Neanderthal variants more than 95% of 23&me users, and our daughter has more than 98% of 23& me users (and does not look at all like a Neanderthal!)

Although we were all taught that the Neandearthals were a completely different type of human (and assumed they were inferior), recent fascinating research has re-created both Neanderthal DNA and that of another ancient human group called the Denisovans, whose ancestral DNA can be found in some people in areas such as Papua New Guinea. Caves have been found with a Neanderthal burial of an old individual who had an old, serious injury and would have been cared for, and whose grave had flowers brought from a distance. It's possible that our ancestors in fact had a skillful knowledge of how to use local plants and animals for food sources to survive the winters. (You can see a re-creation of it at the Smithsonian's Museum of Natural History in Washington, D.C.)

Here's a brief excerpt from an article in the Guardian about a well-respected researcher, David Reich, who along with others has developed techniques that have upended thinking about our family "tree": [emphasis added]
David Reich: ‘Neanderthals were perhaps capable of many modern human behaviours’

Reich's... tests succeeded and subsequently showed, to everyone’s surprise, that many modern humans carry small amounts of Neanderthal DNA in their genomes. “Non-African genomes today are around 1.5 to 2.1% Neanderthal in origin,” he says.

So yes, Homo sapiens and Neanderthals had a common ancestor, about 500,000 years ago, before the former evolved as a separate species – in Africa – and the latter as a different species in Europe. Then around 70,000 years ago, when modern humans emerged from Africa, we encountered the Neanderthals, most probably in the Middle East. We briefly mixed and interbred with them before we continued our slow diaspora across the planet.

In doing so, those early planetary settlers carried Neanderthal DNA with them as they spread out over the world’s four quarters. Hence its presence in all those of non-African origin. By contrast, Neanderthal DNA is absent in people of African origins because they remained in our species’s homeland.

Reich has since established that such interbreeding may have occurred on more than one occasion. More importantly, his studies show that “Neanderthals must have been more like us than we had imagined, perhaps capable of many behaviours that we typically associate with modern humans”. They would, most likely, have had language, culture and sophisticated behaviours. Hence the mutual attraction.
That itself is intriguing. However, there is another key implication of Reich’s work. Previously, it had been commonplace to view human populations arising from ancestral groupings like the trunk of a great tree....Reich believes ... that the standard tree model of populations is basically wrong. Throughout our prehistory, populations have split, reformed, moved on, remixed and interbred and then moved on again...“There was never a single trunk population in the human past. It has been mixtures all the way down.” Instead of a tree, a better metaphor would be a trellis, branching and remixing far back into the past, says Reich.

As for me, I appreciate that nature likes some variety, and hope that we can find ways to control the occasional glitch in the programming!

[mike]

Yes, I've been interested in human evolution since college. DNA has recently allowed for huge strides. The E4 variant would have been perfect for the northern feast and famine cycles that the hunter gatherer Neanderthal would have faced. Evidence is beginning to point to earlier control of fire than previously thought, and Man probably used the extra usable food made available from cooking to expand brain size. Both Neanderthal and modern man have similar brain size. If the 220,000 years timing is correct, and if it happened in Africa, then the Neanderthal would not have the E3 variant. Seems like this could be testable (DNA guys?). Folks have been wondering why modern man displaced the Neanderthal in such a short period... Could it be just a single gene variation allowing for better access to carbs!?

[circular]

I’m not sure, but I think they would already know whether Neanderthals had ApoE4. What I’ve read about is that certain of our HLA genes come from Neanderthals. I figure if Neanderthals were notably ApoE4 we’d already have heard it, but not sure. I think you must be right about that though?

[Anna]

This is something I have wondered too, as a 4/4 with more Neanderthal DNA than 99% of 23andMe users.

I’m not sure, but I think they would already know whether Neanderthals had ApoE4.

I’ve had this thought too but couldn’t find anything difinitive.

[NF52]

This is something I have wondered too, as a 4/4 with more Neanderthal DNA than 99% of 23andMe users.

I’m not sure, but I think they would already know whether Neanderthals had ApoE4.

I’ve had this thought too but couldn’t find anything difinitive.

It seems more likely that some of the earliest hominids had ApoE 4. Remember that some of the highest percentages are found in Nigerian populations, but that people with only African ancestry have no Neanderthal genes.

[mike]

It seems more likely that some of the earliest hominids had ApoE 4. Remember that some of the highest percentages are found in Nigerian populations, but that people with only African ancestry have no Neanderthal genes.

From what I read in the Primer, it sounds like E4 existed before 220,000 years ago, when E3 showed up. It is my understanding that Neanderthal left Africa in the 300,000-600,000 years ago range, prior to the appearance of E3. Did E3 appear in both places at the same time? Unless there was continuous migration out of Africa after 220,000 (not supported by evidence), this seems unlikely. If E3 first appeared in Africa, then it would spread in Africa, but you would still see some E4. In the Case of Nigeria, how much mixing of their DNA with the rest of Africa? Does a single E4 provide some advantage to the Nigerians? Getting AD at 80 was probably not much of a disadvantage... If E3 did first appear in Africa, then what you would NOT see would be E3 in pre-contact Neanderthals in Europe. I can't find anything either way, which means they probably haven't thought to look yet. Someone on this forum attached to folks doing current DNA research? Sounds like a nice PhD thesis!

It makes sense that E3 would come about to make use of a new food source. Fruit is seasonal, and useful to put on fat prior to winter, but there were no year-round carbs available to early man. Man likely had control of fire prior to this point (current research suggests up to 1.5 million years ago), and used it to make use of cooking food to get additional calories. Both Neanderthal and modern man had similar brain sizes, so that particular evolution happened prior to their splitting. They would have been cooking existing food - meat, nuts, etc. that allowed for this brain growth. Tubers without cooking are not eatable, so early man would have ignored them. At some point prior to 220,000 years, but after Neanderthal left for Europe, African man discovered tubers and incorporated into diet. E3 shows up, and is advantageous for those eating carbs year round. Could easily explain why modern man displaced Neanderthal in such a short period.

[Julie G]

I agree with your assessment of early man's diet. I also think it would have included long periods of famine.

We've spoken about the correlation between E4 and Neanderthal before. You may want to do a search. Evolutionarily, it makes perfect sense that we would be higher, but I recall that this didn't hold true for all of us. I'm 4/4 and higher than 94%, low brow and knuckle scraping . I'd love to hear from others who know.

[ru442]

I have more than 98% of those with variants, with less than 4% of Neanderthal DNA, 328 variants. My brow seems normal and my knuckles seem to be OK!

[Julie G]

I have more than 98% of those with variants, with less than 4% of Neanderthal DNA, 328 variants. My brow seems normal and my knuckles seem to be OK!

You're not trying hard enough