28 January 2011

Orangutan genome: details

Genetic retrograde
Irina Yakutenko, The Tape.Roo

On Wednesday, January 26, an article appeared in one of the most authoritative scientific journals – Nature, the authors of which for the first time determined the DNA sequence of an orangutan (Comparative and demographic analysis of orang–utan genomes). A cute monkey with red hair has joined the small list of higher primates whose genomes have been deciphered (in addition to the orangutan, it includes humans and chimpanzees). So far, experts have conducted only a preliminary analysis of the data obtained, but, nevertheless, they have already managed to find a lot of interesting things in them.

Orangutans belong to the subfamily Ponginae, or rather, to its only modern genus Pongo. These monkeys are found only in two places on Earth (not counting zoos) – on the islands of Borneo and Sumatra. Together with humans, chimpanzees, bonobo pygmy chimpanzees and gorillas, the orangutan belongs to the hominid group – the most advanced family of primates. Among the members of this family, Pongo is evolutionarily furthest from humans:

That is why his DNA is especially interesting to scientists – with its help they will be able to consider the evolution of hominids on a full scale.

Until recently, the determination of genome-wide DNA sequences was a very expensive and incredibly labor-intensive process. For example, it took 15 years and about three billion dollars to decipher the human genome (you can read more about how this happened here). The rough determination of the chimpanzee DNA sequence took about four years – the first version of the genome was presented in 2005. The date of the beginning of work with the DNA of an orangutan is not mentioned in the article, but it is reported that the authors have deciphered the genomes of eleven monkeys – six Sumatran animals and five orangutans from Borneo. It was impossible to imagine such a scale even in 2001, when the Human Genome project was completed.

The main object of the new study was a female orangutan named Susie, taken from Sumatra and living in a zoo in Texas. Her genome was decoded "the old-fashioned way" – using the so-called "shotgun method" (if this technology had not been invented, the Human Genome project would hardly have been completed in 2001). The "shotgun" cost the scientists who worked with Suzy's DNA $ 20 million, but the resulting decryption has a decent level of reliability – each "letter" of the genetic code was read an average of 5.5 times. To determine the DNA sequence of the remaining ten animals, the authors used modern and much cheaper technology, but the reliability of the final data was slightly lower.

Dislike of changeScientists conducted a preliminary analysis of the genetic data obtained and found that the orangutan genome is characterized by strange conservatism.

Genetic conservatism means that over time, fewer mutations accumulate in the genome of a particular species than in the genomes of similar species. In this case, the word "mutation" is used without a negative connotation – they serve as the mechanism of evolution. If genomes remained unchanged, organisms would not be able to adapt to unstable environmental conditions, and life on Earth would end as soon as it appeared (or rather, it would not even be able to originate).

Mutations in this case mean not only changes in individual "letters" – nucleotides, but also large-scale permutations in DNA (repeats, permutations or disappearance of individual sites).

In the genome of an orangutan, changes occur much less frequently than in the DNA of humans and chimpanzees. At the moment, researchers cannot unequivocally answer what is the reason for such a retrograde Pongo, but they already have a more or less reasonable hypothesis. The analysis showed that the activity of retrotransposons in the orangutan genome was significantly reduced. This term refers to special fragments of DNA that can move through the genome – their sequence is copied and then embedded in another part of the genome. Some viruses behave in a similar way – in fact, the structure of retrotransposons is very similar to the structure of viral genomes.

When such a mobile element is embedded in its new habitat, it can disrupt the structure of a gene or other important part of the DNA of the host cell. Sometimes such interference has a negative effect on the work of the cell, but in some cases it can lead to the appearance of new useful properties.

One of the types of retrotransposons are the so-called Alu repeats. These elements are very numerous, which means that they can significantly affect the frequency of mutations. The authors of the new work showed that in orangutans, the activity of moving Alu repeats is very much reduced compared to the Alu repeats of chimpanzees and humans. Scientists do not exclude that this feature at least partly determines the conservatism of the Pongo genome.

The work presented in Nature not only raises questions – one of the new results may help explain the mysterious feature of the biology of orangutans. Compared with other hominids – and in general with mammals – these monkeys have markedly reduced metabolic activity. The amount of calories consumed by an active orangutan is comparable to the amount consumed by a sloth spending most of its time in immobility. There is a version that a low level of metabolism was developed in orangutans because of their lifestyle - Pongo eat mainly fruits and often go without food for many days at all.

Researchers have shown that a section of the orangutan genome, which, in particular, controls lipid metabolism (and therefore is associated with metabolic activity), is a "targeted" object of selection. That is, in the course of evolution, individuals mainly survived, bearing certain changes in this region of DNA. The second target of selection turned out to be genes that control vision, which is extremely important for monkeys living in trees.

It is obvious that as the decoded orangutan genome is studied, the number of new facts about this relative of Homo sapiens will increase. And if we consider that projects on decoding the genomes of bonobos and gorillas are already in full swing, then we can hope that in the foreseeable future the history of the most advanced family of animals will become much clearer.

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28.01.2011

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