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In your blog, you have commented on the prospect of re-creating
a neandertal from a "completed" genome.....I agree with your views
and predictions.

However, given the apparent widespread occurrence of small pieces
of the neandertal genome in contemporary humans, there should be
a large variability in the fraction of each person's genome which he/she
shares with at least the small number of neandertals whose DNA has
been sampled.

And though one could argue that ethics would be trampled, one could
selectively breed exisiting humans to enhance their complement of
neandertal genes. Not that I am suggesting this should be done, but
such breeding could be entirely voluntary, may have already occurred,
and would overcome at least some "Jurassic Park" and Frankensteinian
objections to the enterprise??

You bet -- that's not only plausible in principle, it's exactly what people are trying to do with cattle to backbreed something like aurochsen.

The success (not withstanding the time required) hangs on the distribution of Neandertal variation in the current genome. We don't know yet how clustered it is -- is it a 3 percent average, but people have random parts, or is it that most people share the same 3 percent? If it's more scattered, then a larger representation of the Neandertal genome still exists, distributed among many people; if not, we may not be able to get more than a few percent of a Neandertal by backbreeding.

My son, a student at [redacted university], was recently ridiculed by his professor in class when my son suggested that the human brain has been shrinking for the last 20,000 years (the teacher insists that it has not changed). When my son cited the article in September Discover, he was (somewhat understandably) further ridiculed for such a source. My question is: can you provide me with some links to credible sources for this information? He has started to work on this, but wading through so many sources that mention brain size, etc. has proven difficult. We would appreciate any help you could provide.

Thank you for writing -- that is indeed sad but not surprising; I hear all too often from people who have teachers that can't be bothered to read.

The reduction in brain size during the last 10,000 years is a really well-known fact in anthropology, it is not at all controversial. It is, for example, discussed in the introductory-level textbook that I assign my students. I have attached several papers that include primary data from archaeological or historical samples. In Europe the trend is most clearly documented, because of the large number (many thousands) of skeletons that have been studied, but the trend is also apparent in South Africa, China, and Australia. Some of the papers include many other characters that also changed during the same time span.

We cannot rule out that other locations might have had stasis instead of reduction in brain size, but there is not yet a well-documented example of it.

The most common explanations for a reduction in brain size are (a) diet and the consequent reduction in body size; and (b) warmer Holocene climate. Larger brains are always bad, in that they require more development and time, so what we are looking at in the Holocene is a change in the stabilizing selection -- either an intensification of selection against larger brains, or a relaxation in selection against small brains.

Body size also did get smaller during the past 50,000 years, which gives rise to the question of whether the brain has reduced *more than should be expected* from the reduction in body size. My research indicates that it has done so (this was one topic covered in the Discover article), but I would not say this is yet a consensus view.

Re: Neandertal DNA

I have a question about your "Neandertals Live!" entry written on May 8, 2010.

When you say that living non-African populations (ancestry) derive
1-4% of their genomes from Neandertals, does this mean all living
individuals of non-African descent have some genomic contribution from
Neandertals? In other words, could one say if you or myself
specifically have some kind of Neandertal DNA contribution? Or, does
the 1-4% only refer to certain populations outside of Africa, while
nothing can be said about individual non-Africans?

For example, would having Neandertal genes be analogous to certain
populations, like certain ethnicities, having a particular founder
mutation on a haplotype, like sickle-cell anemia in people of African
descent? In other words, some living groups of individuals have them,
but not all living individuals have them?

The comparison results from the greater similarity of European (and other non-African) people to the Neandertal sequence, compared to African people. It takes 1-4% genetic contribution to explain this similarity.

That's an unusual comparison, and it leads to unusual limitations. The number is genome-wide and we don't know (yet) whether some parts of the genome are more consistently Neandertal than others. We also don't know (yet) whether Africans have no Neandertal at all, or just 1-4% less than non-Africans.

We know nothing at all about individuals (at this moment) although I expect we'll be able to say something about the heterogeneity of Neandertal contribution fairly soon.

I expect that some genes will have a very common Neandertal-derived haplotype outside of Africa because of selection, and that these will account for a predominant fraction of the admixture. But I can't say we know this yet empirically.

Re: "Time to revise the mtDNA timescale?":

You said "The timescale of mtDNA divergence is already out of whack with the rest of the genome."

What's the time scale for the rest of the genome? It seems to me it should be expected to be at least twice as much as that for mtDNA since at least half the instances of mtDNA - those in males - dead end each generation. With perfect mixing and replacement, 50% of the mtDNA instances pass from one generation to the next, while 75% of the autosomal instances do. Imperfect mixing and replacement would make both numbers lower, but the mtDNA number would still remain much lower than the autosomal number, so the coalescence time should still be expected to be much lower.

Thanks for noticing that, it's leading to something but I haven't yet described the problem. My apologies for being less than clear.

What you're describing (you probably already know) is commonly described as the "four-times rule" -- the uniparental inheritance and single copy number give mtDNA one fourth the effective size, on expectation, as an autosomal locus.

That's in a constant-sized population. Which of course we haven't been. For around the past 100,000 years, African populations were big enough that genetic drift didn't decrease their genetic diversity markedly. The mtDNA coalesces around 100,000 years before that, compared to more than 700,000 years for the typical autosomal locus -- it's 7 times instead of four. That discrepancy is probably not significant given the huge intrinsic variance of the coalescent. But I don't think it's been seriously investigated.

The real problem is that the out-of-Africa timescale for mtDNA is now very short -- less than 65,000 years -- while the nuclear timescale looks long -- maybe up to 140,000 years. Maybe these can also be reconciled; it's not yet clear. But it's a problem.

Re: australopithecine tools:

Eh, now that I think about it, your bonus prognostication doesn't seem that outlandish. Capuchins use stone tools. I'll repeat that: capuchins use stone tools. You mention chimp technology, and since we use tools - isn't it logical to assume tool manufacture was a trait of the LCA, therefore anything on the lines from the LCA to both chimps and humans had the capacity to make some sort of tool? Without tools and Isaac-approved butchery sites, the more interesting question remains the same: what happened around Gona's antiquity that made hominins start doing things differently than capuchins and chimps?

Yeah, the bonus is never all that unlikely. I still think somebody will find a robust australopithecine in Asia.

It's the mad persistence of Oldowan (and later Acheulean) that gets me. But then maybe it's not really so different from chimpanzees. Honey extraction, bushbaby spearing, and lots of other things are only at one or two field sites. But termite/ant fishing is everywhere. How do they keep that going? I suppose it's partly innate, or they have an innate bias toward learning it. Maybe Oldowan is like that, so there is a biological trigger supporting stone tools in later australopithecines.

Regarding "Bubbling through college":

- - - - and can remember which pages are where.

This alludes to something big that goes largely unnoticed, it seems, and about which I have trouble deciding.

In my own 1960s-80s educated brain, the *location* of knowledge is deeply tied my access to and retention of it. Clearly with online learning and e-books, this means of structuring knowledge goes away, and nothing in particular replaces it. I've lost this strong tendency myself -- I no longer remember a fact, for example, even by *where on the page* the text was located.

But does this matter? Is this "ergonomics" of knowledge essential to all human brains, or is it only a trivial habit developed by a few arbitrary generations in the course of history? Does its loss mean knowledge will be less structured in the future, or merely structured in equally useful but different ways?

I still find myself doing this with PDFs, and I can remember well details of grade-school textbooks this way. But I have no knowledge of how common this may be. It seems to me that we may be exploiting an ancestral "geographic" ability, and it harks back to the "method of loci" which has been a trick for remembering things as far back as Roman times. But how natural is it?

There may be many other kinds of tricks that exploit innate brain abilities that wouldn't ordinarily be recruited for narrative information.

I read some older posts on your blog about dispersal of lactase persistance world wide. Is it not so that everyone can digest lactose at birth and that the production of the enzyme lactase persists as long as milk consumption persists, whether it is human, goat or cows milk? There is also the matter of pasteurization which kills beneficial bacteria that help digest the lactose. Raw milk is better tolerated than pasteurized milk by all populations wordwide, and as far as I can tell; lactose intolerance is actually an intolerance to pasteurized milk.

Even those who drink pasteurized milk have plenty of beneficial bacteria, but bacterial digestion of lactase in the gut is problematic. The bacteria generate lactic acid and CO2, which in large quantities lead to malabsorption of other nutrients and discomfort.

Malabsorption apparently was not a barrier to early dairying peoples; today pastoralists who rely on milk but do not have lactase persistence tend to ferment or culture the milk in ways that cut lactose content.

The target of selection on lactase persistence was likely energy recovery. Lactose accounts for roughly 30 percent of the calories in milk, and increasing the fraction absorbed was probably highly beneficial, particularly for pregnant and lactating women. But some scientists think that the target of selection was the intestinal effect of lactose-absorbing bacteria, as diarrheal diseases exerted a high mortality risk in preindustrial peoples.

Small amounts of milk will not hurt anyone unless they have a milk allergy, which is a separate issue. Lactase production is universal in infants, children's lactase production declines at an age that varies but is usually late childhood or adolescence.