21 May 2008

A supercomputer in a Petri dish

Microbes counted burnt pancakesAlexey Petrov, "Newspaper.

Ru»The ability of the DNA molecule to store information in itself, as well as its ability to self-organize, has already forced engineers and scientists to develop schemes of biological computers and nanorobots based on the "molecule of life".

There are other concepts of biological computers implying the use of self-organizing DNA molecules and their complexes with protein globules in vitro ("in vitro"). However, the computing power of such systems is limited by inanimate systems and does not allow for the proper realization of the possibilities of parallel computing, which are a priori due to the ability of DNA to replicate (double) and divide living cells.

Scientists from the University of Missouri and Davidson College in the USA, led by Carmella Haynes, demonstrated the fundamental possibility of organizing biological computing systems in vivo (in a living organism).

They genetically programmed Escherichia coli bacteria to solve a classical mathematical problem, which, for persuasiveness and clarity, mathematicians call the problem of burnt pancakes.

The scientists' work has been accepted for publication in the Journal of Biological Engineering (temporary link).

The problem can be illustrated as follows: there are several pancakes stacked in a traditional pancake stack. At the same time, all the pancakes on one side are burnt and all differ in size. It is necessary to arrange the pancakes in the minimum number of steps and lay out the stack in descending order of the size of the pancake, and all the pancakes in the final stack should be turned with the burnt side down. In one step, you can flip one pancake or a small stack of them. The answer to the problem should be the minimum number of permutations.

The pancake problem is of fundamental importance for many aspects of computational mathematics. In biology, and especially synthetic biology, which aims to create artificial living systems from individual parts, the problem of sorting using appeals and permutations (namely, the problem of burnt pancakes is called in a scientific way) is of particular importance in comparative genomics. This area of the study of the genome aims to identify the patterns of evolution by comparing the genomes of both very close and very distant taxonomically species.

The fact is that the evolutionary distance between two synentic genes (genes having the same location on the chromosomes of organisms belonging to different taxa) is determined by the minimum of permutations and reversals necessary to sort the gene sections of one organism to coincide with the order and orientation of the components of a related gene of a taxonomically distinct organism.

You can stack n burnt pancakes in a stack of 2 n n! in ways. The number of possible permutations in such a stack is even greater. The rapid increase in the number of possible permutations with an increase in the number of elements significantly complicates the process of calculating the minimum required number of permutations to establish a correspondence between two genes. Even if a million billion operations are performed every second (10-15 operations, petaflop), then the lifetime of the Universe will not be enough to sort through the options for arranging hundreds of elements. There are 300 times more genes in the human genome alone, and 30 million times more nitrogenous bases.

At the same time, plasmid DNA replication and exponential growth in the number of bacterial cells in the nutrient medium open up the prospect of using bacteria to solve the problem of conversions and permutations – it takes less time and space and is much simpler than using silicon computer algorithms.

Where is the connection between burnt pancakes and E.coli bacteria?

In their experiment, the scientists provided the DNA of bacteria with modular sections – "pancakes", which are subject to circulation and have different lengths. The role of the ruddy and burnt sides of the pancake is assumed by the remnants of saccharide bridges on both sides of the modules: each DNA fragment has one end called 3', and the second 5' – the difference is due to a slight difference in the configuration of deoxyribose molecules at the left and right ends of the fragment.

The cellular DNA control mechanism allows you to rearrange and reverse the orientation of various DNA blocks. Of all living organisms, bacteria have been particularly successful in this art, for which the transfer of genes from one species to another is more than in the order of things. The corresponding cellular mechanics is particularly well developed in salmonella Salmonella typhimurium.

E.coli bacteria do not have such a DNA recombination system, but they are excellent objects for observation, so scientists carried out their genetic modification and equipped them with a salmonella DNA recombination apparatus. Thus, E.coli DNA obtained fragments similar to burnt pancakes, and tools for turning them over.

It remained only to make this genetic apparatus work – to turn over and build "pancake fragments" in the necessary sequence.

To do this, scientists have established constant pressure on experimental strains from the antibiotic tetracycline, toxic to E.coli.

The bacteria were also equipped with a gene that causes resistance to the action of an antibiotic, but its activity was manifested only if all the DNA blocks ("burnt pancakes") were arranged in the right sequence and correctly oriented. Only those E.coli that manage to do this faster than tetracycline will kill them survive. And it is those who make the permutation faster than others that will multiply faster.

Each revolution, regardless of the length of the fragment, takes a certain well-known time for bacteria. This means that according to the minimum time required for any one E.coli to rearrange DNA fragments in the desired sequence, it is possible to determine the minimum number of permutations and appeals to trigger the mechanism of resistance to the action of an antibiotic. It is in this way that bacteria allow us to solve the problem of burnt pancakes.

According to the authors of the study, such biological calculations in a Petri dish containing billions of bacteria allow you to run parallel calculations: each bacterium in this case is a kind of biological computer. It is possible to solve rather complex combinatorial problems in this way much more efficiently with the help of live systems.

However, it is hardly worth thinking that someday bacteria will replace millions of computers around the world - the versatility of silicon devices is still significantly higher.

Portal "Eternal youth" www.vechnayamolodost.ru21.05.2008

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