05 July 2010

Ten thousand animal genomes

Genome Hunters
Grigory Tarasevich, Russian Reporter magazineThis project can be put on a par with the Large Hadron Collider or even with a flight into space.

Biologists from all over the world, united, plan to decode ten thousand genomes of vertebrates. Now more than fifty laboratories and research centers are participating in the 10K Genomes project. Russia is currently represented by only one structure – the Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences.

Girls, a gift for you. Let's put it in the refrigerator quickly. – Biologist Vladimir Trifonov enters the laboratory, holding a bone with pieces of bright red meat in his hands. The bone is wrapped in polyethylene, on which the price tag is visible.

We are interested in why cytogenetics need this meat – obviously it's not broth to cook.

– This is a deer, such a deer, – Vladimir explains. – It turns out that you can buy deer meat in our supermarket. It is not much more expensive than beef or pork. We are interested in one of the genes of this animal. Let's try to sequence it....

Library named after the nucleotideA medieval peasant kept only one book at home – the Book of Hours.

Sometimes there is also a psalter or the lives of saints. And now anyone can build a personal library of hundreds of volumes.

The genome of a living being is also a book, only instead of letters, it contains nucleotides that record individual chapters – genes. Now on the shelf of scientific knowledge is the main book – the fully decoded human genome. This text of three billion nucleotides can be equated with the Bible.

Besides him, the genomes of several dozen organisms, from yeast to possum, have now been read – there is something to look through before going to bed. But it's still not enough for a full-fledged library. More than a million species of living creatures crawl, swim and run around our planet. And everyone's genes are a unique work of art.

Remember this name: 10K Genomes. Now this international project is known only in narrow biological circles, but in five to ten years it may become a hero of the first-page news, like the human genome or the cloned Dolly sheep.

The main idea is to read ten thousand genomes of different vertebrate species. The main inspirers were three Americans: David Hassler from the University of California at Santa Cruz, Stephen O'Brien from the National Cancer Institute and Oliver Ryder from the scientific department of the Zoo in San Diego.

– 50 laboratories have united: in addition to American, there are several European, Australian, Chinese have recently joined ... – says Alexander Grafodatsky (a damn charming man with a long position: head of the laboratory of animal cytogenetics of the Department of Molecular and Cellular Biology of the Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences). In the first composition of the organizing committee, he was the only non-American, thanks to which the project was called international.

Photo: Valery Klamm

– Americans – they're dudes. When they decided to expand the project, they asked me: is there science in Europe too? I answered: it is quite there…

Such tasks can only be solved by the whole world. Ten thousand animals is not just one sample. The resulting volume of data will amount to millions of gigabytes: this text will be more than the contents of all the books stored in the Library of Congress, the National Library of China and our Leninka.

The consolation is that reading genes is gradually getting cheaper. The human genome cost at least three billion dollars. But as a result, new technologies have appeared, faster and more economical, and now it takes not billions, but hundreds of thousands to decipher one genome. Well, the goal for the coming years is set as follows: "One genome for a thousand dollars and one day."

– I think in ten years the decoding of the genome will become as accessible as ultrasound in a polyclinic now, – says Alexander Grafodatsky. He believes that the main part of the project can be completed in two to three years from the moment of its launch.

However, just getting a sequence of nucleotide letters is half the battle. Even a very stupid typist can rat out the text of the "Criticism of Pure Reason" or the technical description of a thermonuclear reactor. Another thing is to analyze, understand the meaning and learn how to work with it. It takes many years, many heads and many hundreds of millions of dollars.

"Send me an elephant, a rhinoceros, a giraffe and a zebra..."

To read a lot of books, you need a good library. To decipher ten thousand animal genomes, you need to have samples of their cells. This is exactly what the project participants are doing right now – collecting and cataloging the basis of the future genomic zoo.

– Have you read Dan Brown? – Grafodatsky is interested in me. I don't quite understand what the author of detective stories about Freemasons and descendants of Christ has to do with it, but I nod just in case. – Remember, he has the Smithsonian Institution there with a huge collection that has everything. So, this institute really exists and they have a lot of things. And I am very flattered that our collection of DNA and tissue samples is comparable to the one they have.

I timidly ask if it is possible to look at this meeting. There is an underground bunker, locks, ciphers, security…

– Yes, easily, – Grafodatsky answers, – let's go, it's close here.

No bunker, just the next office. There are two metal barrels at the entrance – beer is delivered to bars in similar containers. There are about ten thousand biological samples sorted into test tubes immersed in liquid nitrogen. Everything is numbered, like in a good library.

– What we don't have here! – Grafodatsky's eyes light up like a real collector's. – Here is my American colleague Steve O'Brien – he deals with cats. And I have half a liter of sperm of the Ussuri tiger stored here for him. I'm still waiting for him to pick it up. And the other day they sent the fabrics of some completely unusual African porcupine…

In theory, a real biologist should run through the jungle with a net and net, catching something exotic. Grafodatsky is not running anywhere. He is sitting in his office, which does not prevent him from receiving samples from all over the world.

– In my youth, of course, I went on many expeditions. But now I try not to go anywhere. Why? Because "his yellow eye is burning, everyone brings it to him and says thank you," he proudly quotes Okudzhava's song. – You see, I have good connections. You write, for example, to a person somewhere in South Africa: they sent, they say, an elephant, a rhinoceros, a giraffe and a zebra.

To get the right tissue or DNA samples, scientists have to go to various tricks. For example, in exchange for a piece of behemoth, your last name can be placed among the co–authors of a scientific publication about the genes of this behemoth - the scientific rating will increase. Somewhere you have to change: you give us a hippo, we give you a deer. Scientists prefer not to disclose some schemes at all.

– Not so long ago, a new animal was discovered in Vietnam, called saola. This is a relative of the cow, very similar to the Tyanitolkaya. Local scientists are trying to sell her fabrics to Americans: the material is still unusual," says Grafodatsky. – And my little Vietnamese friends do not know that already the next year after they described their saola, its cell culture was lying on my table here. In the future, it will definitely come in handy for something, for the same sequencing.

– And how did you get it?

– Well, tell you everything! I have many friends…

Whales and other ungulatesThere is such a genre – a family saga, take at least "One Hundred Years of Solitude" or "The Saga of Forsytes": a crowd of heroes who are each other's five cousins or eight–cousins, are scattered around the world - it can be very interesting to follow all this.

Similarly, it is interesting to analyze the biographies of species. What is the relationship between an elephant and a shrew? Who is a pig to a camel? This is one of the tasks of the 10K Genomes project.

Cow jumps out of ocean waters… I saw this picture on the screen of Anastasia Kulemzina, an employee of the laboratory of animal cytogenetics, who recently defended her PhD thesis on genetic kinship among artiodactyls. Analyzing the chromosomes, she established who, when and from whom came.

The most unexpected thesis: hippos, cows, pigs and other land creatures are the closest relatives of whales. And now it is already proposed to remove the orders of artiodactyls and cetaceans from the classification, replacing them with a single order of cetaceans.

In the early noughties, paleontologists were the first to talk about this, but molecular biologists confirmed the hypothesis. So, about sixty million years ago, camels sprouted from the common ancestor of artiodactyls, followed by pigs, then hippos, and whales from them. All this can be read in the genome.

– Our data confirm that whales really belong to the order of artiodactyls. But we didn't find a single rearrangement in the chromosomes that would be common to hippos and whales.…

So, perhaps, whales are not the younger brothers of hippos, but quite full members of the artiodactyl community. Moreover, there are also contenders for the title of transitional form. About fifty million years ago, for example, a creature called indochius roamed the shores. Outwardly, it resembled a long-legged rat, but some of its bones exactly match those of a whale. It is assumed that indochius hid in the sea from predators, and his descendants got so comfortable there that they were able to give up wool, paws and claws. Another candidate for whale ancestors is pakicetid: he looked more like a dog, only with hooves on his legs and a long tail…

The study of genomes will allow you to learn a lot about kinship relationships in the animal world. Alexander Grafodatsky points to the computer – there is no longer an ocean cow, but some kind of strange beast: paws with huge claws, long ears and a completely piggy piglet.

– This is my beloved, dearly adored aardvark. It lives in Africa. When Georges Cuvier was brought the skin of this beast for the first time, he was sure that the students were playing him: well, this can't be in nature! It turned out that it could. And now, thanks to molecular biologists, it has been established that this is a relative of elephants. Moreover, in the same Africa there is an animal called a golden-mouthed. Both in appearance and in size is really a mole. And we looked at his genome – it turned out that he is also a direct relative of elephants, and has nothing to do with moles. All this is a single superorder – afrotheria, which includes huge elephants, tiny African jumpers, and manatees living in the water.

However, not everything is clear even now. For example, in South America, guinea pigs, monkeys and many other animals appeared forty million years ago, very similar to those that live in Africa. But by this time the continents had already dispersed – there was a deep ocean between them.

– I have heard the theory that, they say, they traveled for a long time from Africa through Asia, Australia and Antarctica, which was still densely populated at that time, until they eventually reached South America. There are no material traces of this migration – you might as well say that they built a balloon and flew across the ocean," Grafodatsky smiles skeptically.

There are many such mysteries in the history of evolution. But with ten thousand decoded genomes on hand, it will be possible to learn a lot about what has happened in nature over the past half a billion years.

Let the roe deer share the recipeNatural selection is the best remedy for all diseases (especially when compared with dietary supplements).

When an animal cannot fight infections or malfunctions in the body, it dies. But if there is something in the genes that allows you to resist diseases, there is a chance to pass on your inheritance to your descendants. Over millions of years of evolution, each species has received its own set of genetic drugs. Finding them is another goal of the 10K Genomes project.

– By deciphering thousands of animal genomes, we will be able to do absolutely fantastic things. For example, some species don't seem to have cancer very much," Grafodatsky reflects. - why? The root cause should be looked for in the genome. Or take the same naked digger…

Immediately a certain subject appears with a shovel in his hands, naked, sweaty and smeared with clay. But scientists are referring to the African rodent. He, of course, is no different in beauty: a kind of well-fed rat, covered with wrinkled gray-pink skin. But appearance is not the main thing. More importantly, this naked digger does not seem to age at all, which excites world science. Some individuals live for almost thirty years – at their size, this is equivalent to if a person lived to 500-800 years. This creature dies solely because of external causes: it will catch an infection or someone will kill it with a shovel.

Scientists from Belgium, the USA and the UK a couple of years ago already came up with a proposal to completely decipher the genome of the naked digger. But they did not receive funding. Perhaps, within the framework of a common project, it will be possible to solve this problem.

You can look for natural recipes for longevity not only in distant Africa.

– Do you want me to tell you the latest news, literally from the heat of the heat? – Alexander Grafodatsky smiles. – My guys recently discovered that one of the roe deer's genes has been changed, and this seems to allow her to fight a heart attack. For everyone else – from chicken to human – this gene is stable, but for some reason the roe deer is modified. Can you imagine?!

Now the laboratory staff is trying to find an anti-infarction gene in other representatives of the deer family. Just for this, a deer bone was needed, which was brought to the laboratory by one of the employees.

Such examples can be ad infinitum.

– Well, why do the same artiodactyls give birth painlessly, and a man in agony, as if the Lord cursed him so?! Grafodatsky exclaims. – I suspect that it's a mutation of literally one or two genes. Man in general is a surprisingly primitive creature, everything is bad for him.

If you continue the comparison with the library, then you can imagine that you are looking for a tastier recipe from books. And it does not necessarily have to be a culinary guide – similar descriptions can be found in "Harry Potter" and "Dead Souls". It is unclear only whether it will be possible to cook this dish in your kitchen.

Theoretically, it is possible to collect the best genes from all over the animal world and get a superman – healthy, strong, with a fine nose and sharp eyesight. Only here's how to insert someone else's heredity into our humble organism?

Since the late 90s, doctors have been talking with fervor about genetic therapy. It would seem that it is easier to find the "wrong" gene, replace it with a healthy one, and thousands of diseases will be forgotten like a terrible dream.

But not everything is so simple. First, the "right" gene should spread through the cells, and preferably not all, but only in a specific organ. Secondly, it is necessary that manipulations with DNA do not provoke a complication in the form of oncology. It's better to live with color blindness than to die of cancer, perfectly distinguishing colors.

Gene therapy, of course, is developing. There are already cured (although there are much more of them among rats and dogs than among humans). But everything is going much slower than expected. It is possible that here, too, the experience of other animals will help a person.

– What if we don't touch the genome? Grafodatsky reflects. – Look, foxes, roe deer, and some species of monkeys sometimes have so-called additional chromosomes. They don't seem to affect anything: you can remove them, add them – the fox won't turn into a goat from this. But it turns out that these chromosomes contain full-fledged copies of genes important for development. And then the idea arises: why not try to insert corrected genes into them?! Moreover, these additional chromosomes – although very small – have sometimes begun to be found in humans…

Perhaps a library of ten thousand genomes will not save you from all the sores. But it will at least give scientists ideas and inspiration, and that's not bad.


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