Tuesday, April 24, 2012

Lessons From Ötzi, the Tyrolean Ice Man. Part III

There are two reasons why I chose this time to write about Otzi.  The first is that I've been looking for a good excuse to revisit human evolutionary history, particularly that of Europeans, and what it does and doesn't tell us about the "optimal" human diet.  The second is that Otzi's full genome was sequenced and described in a recent issue of Nature Communications (1).  A "genome" is the full complement of genes an organism carries.  So what that means is that researchers have sequenced almost all of his genes. 


I have a background in genetics, but genetic anthropology is complicated and it isn't my field.  Some of what I'll present in coming posts is still vigorously debated in anthropology circles, and I don't know the details of all the arguments.  I'll do my best to present the science as I understand it, and if you happen to be a genetic anthropologist and you have a different perspective, please share it in the comments.

Otzi's Mitochondrial Genome

The first genetic information we have about Otzi predates the recent paper by 18 years.  Mitochondria are the cell's tiny power plants, and they have their own tiny genome that's passed down through the maternal lineage.  In 1994, a German group published the first analysis of his mitochondrial genome, indicating that Otzi is genetically related to present-day Europeans (2).  Later papers described his full mitochondrial genome (3, 4). 

Modern-day people are divided into mitochondrial "haplogroups", which simply indicates relatedness through the maternal lineage.  What these papers found is that Otzi belongs to haplogroup K, a haplotype that's present in about 6 percent of people in Europe and the Near East today.  Haplogroup K originated about 16,000 years ago near the cradle of agriculture in the Middle East, and spread outward from there.  It has been found in the remains of early agricultural populations in the Middle East and Europe (5, 6, 7, 8).

These mitochondrial studies indicate that Otzi was, at least in part, a genetic migrant descended from early agriculturalists in the Middle East, rather than a full descendant of local hunter-gatherer populations in Europe that adopted agriculture over time. 

Otzi's Nuclear Genome

The "nuclear genome" is the complement of genes that's contained in the nucleus, and it represents by far the lion's share of a person's genetic material.  This is what the recent paper reported sequencing (9).  It contains a number of insights:
  • Otzi is most closely related to modern-day Sardinians.
  • Otzi had several genetic cardiovascular disease risk factors that collectively would have put him at a substantially elevated risk of having a heart attack or stroke.  This may explain his vascular disease, at least in part.
  • Otzi probably had Lyme disease, a chronic and serious bacterial infection transmitted by ticks.
  • Otzi probably had brown eyes.
  • Otzi was lactose intolerant.
  • "...Otzi carried a large genomic region known as the ‘Y chromosome’, which significantly increases the risk of traipsing about in the a*se-end of nowhere with very little protective clothing, and getting shot by arrows" (10)
In addition, his Y chromosome indicated that his paternal lineage (haplogroup G) also has roots in early agricultural populations in the Middle East.  This is the same lineage that has been found in other early agricultural remains in Europe (11).  This is consistent with his mitochondrial genome and indicates that he descended in large part from early adopters of agriculture in the Middle East.

Why do We Care about Otzi's Genome?

I'm going to begin to answer that question with a question.  What was a man of Middle Eastern agriculturalist descent doing on the border of Italy and Austria 5,300 years ago?  And what were genes originating from early Middle Eastern agriculturalists doing in many other parts of Europe as early as 8,000 years ago (12)?  These findings, among many others, suggest that agricultural populations from the Middle East not only brought their subsistence strategy to Europe, they also brought their genes. 

Researchers have found that Paleolithic humans and neanderthals in Europe had a diet that was heavily focused on meat (13, 14), and this has been used to suggest that modern-day people of European descent should eat a meat-heavy, low carbohydrate diet to mimic their own ancestral dietary pattern.  But this makes a big assumption: that those Paleolithic meat eaters were the ancestors of modern-day Europeans. If instead, modern Europeans descend from Middle Eastern agriculturalists who originally came from Africa, that means they were never hunter-gatherers in Europe and therefore never ate a diet focused on meat and fat-rich large temperate game.  If they descended from Middle Eastern agriculturalists who ate a high-carbohydrate grain-based diet for some 10,000 years, this may lead to different conclusions about the ancestral European diet.

In future posts, I'll explore what research has uncovered about European ancestry, human evolution since the development of agriculture, and what that means for the human dietary niche. 

39 comments:

Eimear said...

Your final point makes an assumption- that Otzi's genetic ancestry was the same as everyone else in 'Europe' at that time. Some of that genetic material is almost certainly preserved in the gene pool, unless those middle Easterners killed everyone they found. There may well have been people who were living there and not descended from middle Eastern agriculturists, and they may have learnt about agriculture from middle Easterners rather than being wholly supplanted by them.
Also, what were the middle East agriculturists before they became agriculturists? This is the problem with paleolithic dieting. At what point in time do you decide your ancestors' diet it worth 'aping'?

Eva said...

Eimar, I don't think he's made any such assumption just yet. Sounds like data on overall European ancestry from various sources is coming in upcoming posts. However, if the presumption turns out to be that Otzi's genetics had 10,000 more years to adapt to grain eating, I would guess that those 10,000 years would have had some effect on his ability to process grain. Evolution does not stop. However, evolution also no way has been able to keep up with the very recent influx of crap we now eat. As often happens the truth probably lies somehwere in the middle.

Heath said...

For me, it isn't so much about whether an assumption of ancestry was made. It's more that it complicates the "paleo" question so as to nullify it. At least in my mind. It makes it mostly irrelevent.

Heath said...

*irrelevant

Hi Eimear! Yay Gummy bears!

Continuing on in that line of thought, we have no idea whose genes are whose. While we don't have hard evidence, it seems like everyone was sleeping with everyone else.

It seems like it's becoming apparent that our "genetic heritage" is our adaptability. Not necessarily our ability to run on GNG and lipids.

Nigel Kinbrum said...

Why don't people just "Eat, monitor and adjust accordingly"?

It's not exactly....y'know!

Breastlight said...
This comment has been removed by the author.
Breastlight said...

well this is totaly new information for me on this blog. i visit thgis blog first time and found it really interesting.

Breast awareness

Mrs. Ed said...

All of this is so interesting. I would like to learn more about mitochondrial genome. They have found a lot of mitochondrial issues in autism, and autism can run in families (three generations of my own). Is there any equivilance to an idiots guide to the mitochondrial genome that you could recommend?

Txomin said...

The difference between one or the other ancestry is just a few thousand years. Ultimately, agriculturalist have not been around for that long, comparatively speaking.

BHI said...

And yet they have been around long enough to allow us to ADAPT to many extremes of climate and diet and still thrive.

Stephan Guyenet said...

Hi Eimear,

I'm not making that assumption. We'll get there.

Geoff said...

Otzi is only 5,500 years old, and early Middle Eastern agriculturalists are at most 16,000 years old. If the paleo hypothesis predicts that 10,000 years is not enough to cause a complete adaptation to grain agriculture in modern humans, why would tacking on an extra 5,000 years make a significant difference?

Regardless of which population modern Europeans descended from, they were still hunter-gatherer homo-sapiens for 150,000 years prior, and homo-erectus/habilus/etc. for 2 million years before that.

Maybe this is my way of declaring shenanigans on population specific ancestral diets in general...

Cassandra said...

I'm a new reader (near Seattle too!) and I want to express my appreciation for this series you're doing. I became interested in genetics playing a part in nutrition when I read Native Nutrition by Ron Schmid, but haven't been able to find much more that covers the topic (online and at the library anyway). Really looking forward to more about Otzi.

Edwin said...

Hello Stephan!
I am a regular reader of your blogg and I thought that you might find this information interesting:

205 school going children (80 boys, 125 girls) were tested and got their cheek swabs analysed by 'The Genographic Project'. The children were from across The Netherlands (my home country) and were made public by prof. dr. Peter de Knijf of Leiden University.

I guess by the comment de Knijff the sample size is big enough and thus have any value for you, but the professor said that it might suggest that the hunter gatherer population adopted agricultural practices instead of being supplanted by the 'newcomers' who arrived 7000 years ago (he clearly said he wished for more samples).

According to de Knijff 78% of the children are claimed to have (paleolithic/)hunter gatherer ancestry and almost the rest farmer(/neolithic) ancestry. 2,5% of the sample was of recent immigration, mostly from Asia.

I got this information out of a newspaper article from 2008. It is also stated that the population from Spain, France and Belgium was, like in The Netherlands predominantly of hunter-gatherer origin and Germany was predominantly of 'Farmer' origin.

And a funny commercial :-p
http://www.youtube.com/watch?v=H4Zd9kEIrMk&feature=player_embedded
Is that what dutchmen should do? hehe

I hope this was at least of some interest to you.

Greetings,

Edwin

Nick said...

I don't find it surprising that there's more evidence European HGs were supplanted by agriculturalists from the east. How many examples do we have of agriculturalists interacting with HGs where the HGs don't end up exterminated? Not many. While 10ky of agriculture may have lent some of us adult lactose tolerance and a few more alpha-amylase copies, I'm not sure it necessarily follows that our genetically optimal diet includes milk and grains, merely that we can tolerate them.

Edwin said...

Hello Stephan,

I thought I just posted a comment but I don't see it so I think I did something wrong (sorry, first post here). But anyways, here is it again (or not). You can delete this or the other post, wichever you prefer.

Back in 2008 within the cadre of the Genographic Project 205 Dutch boys and girls from across the country were tested. Prof. dr. Peter de Knijff of Leiden University made public that approximately 78% of the sample were of 'hunter gatherer/paleolithic' origin and almost 20 percent of 'neolithic/farmer' origin. 2,5 percent was composed of recent immigrants from mainly Asia.

Though he clearly wished for a bigger sample, these results, if consistent with a larger sample, would suggest that instead of being supplanted by the farmers, hunter gatherers adopted the agricultural practices of the 'newcomers' wich are thought to have arrived approximately 7000 years ago.

A newspaper article stated that in countries like Belgium, France and Spain there was also a predominance of hunter gatherer origin. Germany on the other hand is thought to be predominately composed of 'newcomers'.

Could this be overlapping with haplogroup R1b and the first europeans that sought sanctuary in the Iberian peninsula? (Disclaimer: genetics is not my field, I am putting info together. I am a mere student.)

I hope this is of interest of you.

Greetings,

Edwin

Edwin said...

I really tried hard and about an hour or 2 to find any reference because i think my post deserves it but failed to find it sorry :-(

...but i found the same information in an interview with him and several respected dutch newspapers and magazines...all in dutch unfortunately

so take it what i say for what you think it is worth

MJS said...

A new diet book, _The Hunter/Farmer Diet Solution_, offers a quiz to determine if someone's phenotype is more hunter or more farmer. Like most diet books, it's a bit selective in its science. However, it does correspond to some of the Otzi issues.

Rafael. said...

Chimpz eat leafs, flowers and insects to get enough protein and energy (SCFA) and fruits to some sugar. Respectively, 12% of protein, 13% of fat, 55% sugar more starch and 20% SCFA.
In the evolutionary process, I've thought that we replaced leafs, flowers and insects per animals protein and roots, and we kept the fruit consume.
In other words, I've thought that chimpz, bonobos and homo need the same ratio protein, cho, fat. About 1g/kg of protein is optimal for them, so the paleolithic diet didn't differ too much. Our diet always has been based in low protein (10-15%E), moderate fat and high carb. Protein from animals, fat from animals and maybe nuts, and carbs from roots, fruits and maybe grains.

Rafael. said...

In paleolithic, I've suspected that we ate meat but not all the time. About 2kg of game meat per week maybe, split in three times a week on non-consecutives days or twice a week, in the protein average of 75g/d. In the most of time, fruits, roots, grains and nuts were eaten.

George Henderson said...

Just because some europeans cultivated grains 10,000YA, it doesn't mean that the habit spread quickly through the whole vast area.
In peripheral regions like scotland and scandanavia, wheat is a recent crop, and even in northern europe it dates from the late middle ages.
Rye is a bit older, barley was the grain of the classical Greeks; grains thus appear to have spread slowly from their centres of cultivation outwards.

Races adapt when the non-adapted membres die off or stop breeding; to say we are becoming adapted to grains, as some do, is another way of saying that grains are still killing us.

Jane said...

I have big problems with the idea that humans needed to be specially adapted to eat grains. Why? Why wasn't the machinery we already had good enough? As far as I am aware, there is nothing in grains that humans cannot deal with very well unless they have micronutrient deficiencies.

allison said...

I seem to recall reading that mitochondrial DNA analysis strongly indicates that 80 percent of the European gene pool is comprised of the genes of hunter-gatherers, who already occupied Europe when the farmers arrived. Imay have read that in The Seven Daughters of Eve by Bryan Sykes.

George Henderson said...

@ Jane, why would we be adapted to eat grains? They are small things, hard to find in any nourishing quantity, very hard to chew, and designed to go straight through the animals that eat them.
They are the plant's babies and toxins are their only defense.
Avoiding them is easier than eating them. We got lucky with rice, but that was the exception.

frank r said...

@George Henderson: Nuts are trees' babies and toxins are their only defense, but humans and the other apes and monkeys have surely been eating tree nuts for a very long time. Pigs and bears and rodents too. All mammals evolved from rodents originally, didn't they? Also, green plants typically have toxins and also roots. It isn't unreasonable to think that all omnivores have a general-purpose system for handling plant toxins, and that this general-purpose system also works for grains. The system is likely much more powerful in pigs, weaker in humans, due to our much smaller gut relative to our size, and with significant gaps for the borderline carnivore/omnivores, like dogs (dogs can't digest chocolate, for example).

Jane said...

Yes, I think Frank is right. Actually the idea that phytate, gluten and lectins are toxins in the conventional sense is debatable. All three have sensible functions in the developing plant. Gluten stores amino acids for future use, phytate stores phosphorus and metals, and lectins at least in one case bind and store plant hormones so they can be released when they're needed and not before. Packaging up things like this is may be necessary both for survival of the seed and for successful germination.

Jane said...

George, avoiding grains may be easier than eating them, but it seems we ate them anyway, even very small ones.

'..a collection of >90,000 plant remains, recently recovered from the Stone Age site Ohalo II (23,000 B.P), Israel, offers insights into the plant foods of the late Upper Paleolithic... The staple foods of this assemblage were wild grasses... In addition to cereals, the foragers of Ohalo II gathered large quantities of more than 5 different SGG [small-grained grasses] which, like much of the fauna hunted during the Late Paleolithic, were costly to procure compared with the returns.'
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC470712/pdf/1019551.pdf

jacob boyd said...

Here is an interesting article about more samples from the paleo/neolithic transition and spread throughout Europe in Discover Magazine.

Robert Andrew Brown said...

Thanks Stephan (-: - thought provoking material as always.

Great links Jacob and Jane - fascinating material.

It looks like seeds etc have figured in the diet for a long time, even only if in small proportions.

The Hunza ate grain and were reported to be very healthy, so the value of grain as a food source, and health and development impact, may depend on preparation, wider dietary context and overall nutrient availability.


http://www.pnas.org/content/early/2010/12/17/1016868108.full.pdf+html

"The nature and causes of the disappearance of Neanderthals and
their apparent replacement by modern humans are subjects of
considerable debate. Many researchers have proposed biologically
or technologically mediated dietary differences between the
two groups as one of the fundamental causes of Neanderthal
disappearance. Some scenarios have focused on the apparent lack
of plant foods in Neanderthal diets. Here we report direct
evidence for Neanderthal consumption of a variety of plant
foods, in the form of phytoliths and starch grains recovered from
dental calculus of Neanderthal skeletons from Shanidar Cave,
Iraq, and Spy Cave, Belgium. Some of the plants are typical of
recent modern human diets, including date palms (Phoenix spp.),
legumes, and grass seeds (Triticeae), whereas others are known to
be edible but are not heavily used today. Many of the grass seed
starches showed damage that is a distinctive marker of cooking.
Our results indicate that in both warm eastern Mediterranean and
cold northwestern European climates, and across their latitudinal
range, Neanderthals made use of the diverse plant foods available
in their local environment and transformed them into more
easily digestible foodstuffs in part through cooking them, suggesting
an overall sophistication in Neanderthal dietary regimes"

Sara said...

Does anyone know if these ancient genotypes relate at all to blood type?

Sara said...

Also.. LMAO at the risk factors correlating with the Y chromosome. :D Who doesn't love a bit of bio-geek humour.

Nyx said...

You asked: What was a man of Middle Eastern agriculturalist descent doing on the border of Italy and Austria 5,300 years ago? I wondered. Wikipedia (I know, not very scholarly) says the Ancient Near East "created a centralized government, law codes, and empires, and introduced social stratification, slavery, and organized warfare." Hmm. I might have headed west also.

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Peter said...

Nice one Stephen. Atleast the germanic-speaking Scandinavia is completely of neolithic origins:


Ancient DNA Reveals Lack of Continuity between Neolithic Hunter-Gatherers and Contemporary Scandinavians

http://www.cell.com/current-biology/retrieve/pii/S0960982209016947

Eva said...

I would not make the argument that there has been enough time for complete adaptation to grain as being equally as healthy as a more paleo type diet. But it bears keeping in mind that evolution can happen quickly and there can still be a lot of adaptation over 10,000 years. That's why you can see such a diff response to things like alcohol and grains in the diets of peoples like the Pima Indians compared to the average European genetic response to same. The Europeans have had more time to adapt/evolve to tolerate those foods. The evidence of neolithic dietary evolution is all around us even today.

Txomin said...

Grains are not edible unless cooked. As a species, and as any other species, we are adapted to eat what is edible as found.

Jane said...

@Txomin

Uncooked grains are edible if they're sprouted. I don't know if any sites have been found with evidence for grain gathering but no grinding stones.

I can't imagine that even our earliest ancestors hadn't noticed that grains turn into delicious little plants if you add water.

Amarjeet Prasad said...

Thank you for your analysis and sharing, from your article I learned more.

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G Nettick-Lea (confused) said...

Fascinating stuff, I've been searching for ages for a scientific approach to genes and diet and this discussion has that.

European is an interesting description for a very diverse land area and ethnic mix. I am pure English, so my blood is a mixture of that from Neanderthal, French, Viking, Celt, Angle, Saxon, Dane and Roman, together with their North African and German soldiers. My brother might be better at eating roasted pig than me, my diet perhaps needs to be more olive oil and grain, only studying individual genes can show that. And that only when we have learned to read them.

Recently two Sri Lankans who were related to people I knew suffered huge strokes. This shocked me, Sri Lankans were so healthy, no longer. Now they have changed their diet from coconuts fish vegetables and a small amount of brown rice to a more western style high carb diet. Corporate Scientists are there promoting 'healthy' mass produced fats, and telling them to not eat coconuts. Their old diet was healthy, there was almost no heart disease or diabetes. So what I want to know is...should I eat a cup of coconut oil a day or beef dripping or a glug of olive oil?