20 July 2016

We are what they ate

How the eating habits of our ancestors changed our genes

Mikhail Petrov, "The Attic"

For thousands of years, man has adapted to living conditions: weather, predators, the change of day and night and, of course, food. The eating habits of those times are still hidden in our genes. Tatiana Tatarinova, a professor at the University of Southern California, helped the Attic to understand the influence of genes on modern human life.

Dust, heat, a crowd waiting, two boys whipping each other on the backs with whips. This is what the initiation ceremony looks like for the Fulani people living on a vast territory in West Africa. There are variations from village to village in the rite of initiation into men, but the essence is the same everywhere: prove that you are a man with your patience and perseverance.

In 2015, scientists found traces of this cruel custom in the DNA of representatives of the Fulani tribe: their genes encoding taste receptor proteins underwent mutations that reduced the sensitivity of the receptors. It turns out that shortly before the initiation, the boys are given palm beer to drink with such a terrible taste that it can only be sustained after several years of hard training and with a blunted sense of taste. Otherwise, you can't drink this stuff, and it's impossible to endure cruel blows without it.

Therefore, for centuries, evolution has selected men from the Fulani tribe with TAS2R gene mutations that allow for more efficient processing of alkaloids from palm beer and thereby facilitate initiation into adulthood. The rest simply could not stand the blows of the whips: the shame of the "failed" initiation did not allow them to marry and, consequently, leave offspring. The most insensitive will survive.

"The story of Fulani is very vivid and revealing,– says Tatiana Tatarinova. – Taste genes of modern people not only change from people to people, but also differ from Denisov and Neanderthal. For example, today we all like the smell of smoked sausage, but ancient people might not have been interested in it at all."

Fire, earth and milk rivers

Our brain is a very demanding machine. It makes up only 2% of the total body weight, but consumes up to 20% of all energy in the human body: high-performance computing, which once provided a person with the opportunity to communicate, plan their actions and make complex tools, requires a lot of money. Therefore, any innovation that made it possible to extract energy from food more efficiently made a person not so much stronger, faster or more, but smarter: excess energy was spent on the work of our main adaptive organ.

The first and most grandiose gastronomic revolution in the history of mankind is connected with the development of fire and is lost somewhere far away in the centuries. How it all happened then, scientists are still arguing. Some believe that people first developed mutations that allow them to digest fried and boiled food and not be poisoned by the by-products of such heat treatment.

These lucky people could cook the first prehistoric steaks and meatballs using forest fires or the heat of hot springs, get a solid gain in calories from this, and then used it for brain development, which eventually allowed them to master the extraction of fire.

According to another version, ancient people first learned to kindle and maintain a fire in their caves for heating, and only then the most successful of them – the owners of suitable genes – began to cook a little and get an incredible evolutionary advantage from this, which gave them the resources to bear and give birth to more children and populate the territory with their descendants.

There was no one to surprise with the taming of fire in the ancient world: both Neanderthals and Denisovans were able to cook food, and, apparently, even a working person (Homo ergaster), but agriculture turned out to be subject only to a reasonable person and forever changed our DNA. A recent study by American scientists showed that modern humans have an average of six copies of the AMY1 gene encoding the enzyme amylase, while Denisovans or Neanderthals have only two diploid copies. Saliva amylase hydrolyzes starch and glycogen in the oral cavity. "Apparently, when agriculture appeared in humans, they gradually had a completely different reaction to starch than other hominids. Neanderthals or Denisovans could not digest wheat or rice so efficiently," Tatarinova says.

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The scheme of kinship between a reasonable man, a Denisovan man and Neanderthals.
Image: Nature, translation: "Attic"

Man is the only mammal capable of consuming dairy products in adulthood, after switching to solid food. Others can drink milk only in childhood, and then the genes responsible for lactose processing will turn off so that the grown-up cubs do not follow their mother all their lives and she can feed new offspring. The same thing used to be observed in humans, but then they tamed cows, goats and sheep, and so, gradually, humanity began to get used to milk consumption.

"According to anthropological data, cows were tamed about 10 thousand years ago, and genes for milk processing appeared about 5 thousand years ago," Tatarinova says. "For five thousand years, people kept cows, produced and ate cheese, but could not drink whole milk."

It is not difficult to explain such a time delay. After all, each gene can exist in several variants at once, or, as scientists say, in "alleles". All cells of the human body, except for sex, contain two alleles of each gene at once – they carry two sets of chromosomes. If these alleles differ and contain different instructions for the synthesis of the same protein, then the body will follow only one of these instructions – the dominant one. For example, a person with two alleles of the gene that determines eye color – blue and brown – will have brown eyes, because the allele of brown eyes is dominant, and the allele of blue eyes is recessive (this is a simplified description of the case of complete dominance. In reality, the body may seem to be trying to execute two instructions at once, and the eyes will turn green – this case is called incomplete dominance).

Therefore, even the most profitable genetic innovation in humans cannot quickly gain a foothold. First, several people should accidentally have a mutant allele, the effect of which will most likely be suppressed by other, dominant variants of the gene in relation to it. Then two "mutants" should meet and produce offspring who will have two copies of the new allele at once. These descendants must grow up, survive and reproduce, and so on.

In total, it takes 150-400 generations (or 3-8 thousand years) for the novelty to gain a foothold in our DNA, and then if it gives its carriers solid advantages in everyday life.

That is why the genes of the lactose enzyme were so slow to take over the world: a genetic study of 13 skeletons found on the Great Hungarian Plain and dated 5700-800 BC showed that all the detected representatives had lactose intolerance.

By the way, this feature is still characteristic of more than half of the world's population. Only residents of the Nordic countries, including Russia, can drink milk and break down lactose: here an unusual mutation that appeared several thousand years ago was especially beneficial. In conditions of a meager diet and a shortage of solar ultraviolet, dairy products have become a key source of energy and trace elements necessary for life and the birth of healthy offspring.

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The color indicates the proportion of people with lactose intolerance in different countries of the world: from green – lactose intolerance is rare, to red – lactose intolerance is widespread. Source: Wikipedia, translation: "Attic".

By the way, a recent study in the journal Nature Genetics showed that there is a significant overlap between the increased genetic diversity of dairy genes in cows, geographical zones of Neolithic sites with the presence of cattle and the current level of lactose tolerance in Europe. So it's not for nothing, apparently, the Dutch have the most delicious cheese!

"In the genomes and food habits of modern people, we observe those factors that appeared 8 thousand years ago, during the transition to the Bronze Age," says Tatarinova.

Bone certificates

In 1994, researchers from Brigham Young University announced that they were able to obtain a fragment of mitochondrial DNA (mtDNA) of a Cretaceous dinosaur from bones 80 million years old.

It was a sensation: humanity had the opportunity to look into the genetic history of the antediluvian world. The reality turned out to be much less interesting: other laboratories could not repeat the results of this study, and the unique fragments of mtDNA found were more similar to human mtDNA than birds or reptiles. Scientists realized that they took the traces of careless laboratory technicians working with samples for prehistoric antiquities.

Such stories often happen when working with ancient DNA (dDNA, ancient DNA, aDNA) not only of dinosaurs, but also of humans. The words in the genetic annals are erased, and the manuscripts themselves fall into pages and are smeared by illiterate barbarians. dDNA molecules gradually shorten under the action of bacterial enzymes that decompose fossils, spontaneously change their structure (for example, cytosine gradually turns into thymine over time) and mix with the DNA of the same bacteria or, for example, wolves who excavated graves to feast on bones. Alas, no media on Earth is eternal.

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Over time, cytosine turns into thymine. Image: "Attic"

Therefore, scientists are very cautious about dDNA research, and the horse of the Middle Pleistocene epoch, which lived somewhere 560-780 thousand years ago, is still considered to be the oldest organism whose DNA has been sequenced. Humanity has not yet got further into the genetic history of the world.

However, you need to be careful when working not only with very ancient DNA.

"If you want to work with the remains of a great–great-grandfather who died in the Battle of Borodino, then you need to take a Chinese or even an African laboratory assistant to the team," Tatarinova says. "Even an experienced researcher can contaminate ancient samples with his DNA, but traces of Africans or Chinese in European data will be easier to weed out by specific mutations."

In addition, a careful analysis of the data will help to distinguish ancient DNA from modern ones, for example, by the very characteristic transformations of cytosine into thymine, which by their nature most often occur at the ends of DNA macromolecules – they are more actively involved in Brownian motion and therefore more reactive. Also, a careful study of ancient DNA should be carried out on several snips at once (from the English abbreviation SNP – single nucleotide polymorphism) and achieve good reproducibility of data for different laboratories and different samples found in the same burial or in the same cemetery.

We also add here the conditions of special "clean rooms" for working with DNA and meticulous bone selection. "Thick and dense bones are better suited for the study, in the depth of the tissues of which bacteria from the environment have almost not penetrated – the tibia, temporal, enamel–protected parts of the tooth," says Tatarinova. As a result, a very expensive and painstaking scheme of the experiment turns out, because there are very few good studies of ancient human DNA so far – even finding several skeletons with suitable bones in one burial is no longer easy.

Anthropologists help geneticists, whose methods of work are much more verified: for example, the diet of our prehistoric ancestors from some excavated site can be restored by the appearance of teeth and the isotopic composition of tissues.

"The ancient DNA is full of garbage, and when working with it, you need to constantly separate the "grains" from the "chaff," Tatarinova says. – Anthropology is still a much more established science, and therefore it is reasonable to take anthropological hypotheses and test them with the help of genetic data. Anthropological data can help to draw, figuratively speaking, a big target for further genetic research. But if an arrow of ancient DNA hits a target on another tree, then, most likely, something is wrong with the genetic data."

Cuisines of the peoples of the world

There is another, much simpler way to look into the kitchen of our ancestors – not to dig into their ancient DNA, but to take a closer look at the heritage, unique tastes and preferences that they left to billions of modern people. So, the diet of the Maasai, a semi–nomadic African people living in the savannahs of Southern Kenya and Northern Tanzania, looks at least strange to us, and at most even deadly.

"The Maasai can eat so much fat and not get fat that I, a European woman on an eternal strict diet, just want to die of envy," says Tatarinova. "On average, they eat six times more fat per day than Europeans, but they still remain thin."

In 1971, scientists decided to test this unusual feature of the Maasai in an experiment. They gathered two groups of subjects aged 20-24 years, each of which included both Maasai and Europeans. Scientists kept people from the control group on a regular diet, while others were added two additional grams of cholesterol per day. After eight weeks of such a diet, the Maasai felt absolutely nothing: the cholesterol content in the blood of the Maasai from both groups was the same within the margin of error.

Europeans were much less lucky: every additional 100 milligrams of cholesterol in the diet increased the level of cholesterol in the blood by 11.8 mg /100 ml (with a norm of 160-250 mg/100 ml). We can only guess how these two–month trials affected the life and health of genetically unprepared Europeans, but one thing is for sure: cholesterol is not a problem for the Maasai. By the way, that is why in their society it is customary to pass off young girls as experienced 60-year-old and 70-year-old men who are not burdened with excess weight, problems with cardiovascular diseases and, most importantly, are quite capable of leaving behind healthy offspring.

Many centuries of natural selection have left only the fittest Maasai – those who can eat fatty foods and not get themselves major problems with the heart and blood vessels.

Scientists have recently read a story similar to the situation with the Maasai or Fulani in the genes of the Eskimos of Greenland, whom they compared with some peoples of India, South Asia and Africa, historically adhering to a vegetarian diet. Scientists have tracked in these populations the frequency of the allele associated with adaptation to food in the context of omega-3 and omega-6, unsaturated fatty acids necessary for the human body, which a person can get almost only from food.

It turned out that the genes of vegetarians have been honed for centuries for enhanced food processing to extract deficient omega-3 and omega-6 from plant foods, while in Eskimos with their marine diet rich in saturated fatty acids, such mutations are not observed. Being a vegetarian is almost impossible for them.

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The prevalence of alleles adapted for vegetarian food in various countries of the world. Source: Cornell University, translation: "The Attic"

Milk, cholesterol, saturated fatty acids, alcohol – our gastronomic preferences are fixed in the genes and traditions of distant and close ancestors. A careful look at DNA will help in the future to choose the optimal diet for each of the people. Nutrigenetic scientists do not yet have a complete picture of the relationship between genes and nutrition, and it is not easy to conduct new research in this area.

Experiments on modern humans, similar to experiments with Maasai, will not be allowed by ethical commissions, since one of the groups of people will be guaranteed to receive harmful nutrition (like those Europeans fed with cholesterol). The alternatives – ancient DNA research – are still very complex and expensive.

"The cost of sequencing ancient DNA is much higher than modern DNA," Tatarinova says. – Currently, such work in different countries is funded exclusively by fundamental research agencies – little private investment is invested. But it seems to me that commercial companies will soon come to this area, since recreating the genetic picture of the evolution of food habits can significantly affect the food industry."

Moreover, food affects not only our genome, fixing the necessary mutations in it for thousands of years, but also the epigenome: any eaten product changes the activity of our genes in almost real time. About this – in the next part of the material.

About the author:
Tatiana Tatarinova is a professor at the University of Southern California, a member of the Scientific council of the Atlas Biomedical holding and an employee of the Institute of Information Transmission Problems.

Portal "Eternal youth" http://vechnayamolodost.ru  20.07.2016

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