12 November 2020

Are cell nuclei former viruses?

Russian scientists have found evidence of the viral origin of cell nuclei

RNF Press Service

Scientists from MSU and SPbPU for the first time studied how a bacterial cell changes when infected with a giant virus of bacteria – phiKZ bacteriophage. It turned out that as the pseudonucleus formed by the phage matures during infection, a dense network of strands of viral DNA and proteins appears inside it, functionally resembling DNA packaging in the nuclei of living organisms. This may speak in favor of the theory that the cell nuclei of both humans and other animals, as well as plants, have a viral origin. The results of the work supported by a grant from the Presidential Program of the Russian Science Foundation are published in the journal Viruses (Danilova et al., Maturation of Pseudo-Nucleus Compartment in P.aeruginosa, Infected with Giant phiKZ Phage). 

phiKZ.jpg

Pseudomonas aeruginosa bacterium infected with phiKZ bacteriophage in the late stages of infection. The image was obtained by electron tomography. Source: Danilova et al. / Viruses, 2020.

The main feature of eukaryotic cells is the nucleus, a special cellular organ made of two membranes that protects DNA. Prokaryotes, on the other hand, are nuclear–free organisms whose nucleoid performs the function of the nucleus. This is the name of the area of the cell containing DNA and saturated with protein. Prokaryotes include, for example, bacteria. Exactly how simple prokaryotes evolved into more complex eukaryotes is still unknown. Nevertheless, it is believed that the appearance of the nucleus was one of the first events on the path of evolution.

Now there are several hypotheses of the origin of the eukaryotic nucleus: from a bacterium captured by a predatory precursor of eukaryotes; from the penetration of its own outer membrane; from a virus that, after infecting the cell, began to control it. According to the latter hypothesis, the virus should have been as large as the cell nucleus. Thus, the existence of giant viruses, such as the smallpox virus or giant amoeba viruses, can be considered an argument in favor of the viral origin of the nucleus. In their work, scientists from Lomonosov Moscow State University (MSU) and Peter the Great St. Petersburg Polytechnic University (SPbPU) found out what happens when Pseudomonas aeruginosa is infected with a giant bacterial virus - bacteriophage phiKZ.

"Some time ago it was shown that the bacteriophage phiKZ forms a spherical compartment inside a bacterial cell during infection, and its size is comparable to the bacterium itself. It is covered with a protein shell, inside which a huge amount of the DNA of this virus is packed, as well as part of the DNA-binding proteins. In shape and intended function, this compartment resembles the nucleus of a eukaryotic cell, which is why it is called a pseudonucleus," says project manager Maria Yakunina, Candidate of Biological Sciences, researcher at the Laboratory of Molecular Microbiology at the Institute of Biomedical Systems and Biotechnology of SPbPU.

In their work, scientists infected bacterial cells with phiKZ bacteriophage. To see what happened, they dyed the virus's DNA and the bacterium's own DNA with fluorescent ("glowing") dyes after certain time intervals. It turned out that bacterial DNA leaves the central position in the cell and goes to the periphery, while its place is gradually taken by viral DNA, which is becoming more and more. The same result was shown by another method – transmission electron microscopy: within five minutes after infection, the nucleoid of the bacterium shifts to the periphery, and after 15 minutes a pseudonuclear with viral DNA appears. From the very beginning of infection, the DNA of the bacteriophage is located inside special spherical compartments, then inside the pseudonucleus and, finally, is transferred to newly formed phage particles. According to the authors, each of these "compartments" effectively separates DNA from the host's defense systems.

New bacteriophages appear 30 minutes after the start of infection. To study the structure of the mature pseudonucleus at this stage, scientists used 3D electron microscopy, or electron tomography. They showed that the three-dimensional organization of phage DNA inside the pseudonucleus resembles a network of DNA-protein complexes. This probably reflects the complex mechanism of compaction of phage DNA, similar to the packaging of eukaryotic DNA.

"We have shown that infection with the phiKZ bacteriophage leads to significant rearrangements inside the bacterial cell, turning the bacterium into something absolutely unlike its former one," comments Maria Yakunina. – The theory of the viral origin of the nucleus is only one of many. However, observing the processes inside a cell infected with the giant phage phiKZ, it is quite easy to imagine that this could really have happened many, many centuries ago (so in the text – VM). At the same time, there is a high probability that the proteins inside the pseudonucleus perform a function similar to that of histones when packing DNA in the nucleus of a eukaryotic cell."

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