Viruses bring new genes to the human genome
To adapt to new conditions during evolution, organisms change genetically, among other things, and new genes are formed. Viruses, which are grouped under inanimate nature, contribute to the genetic diversity of living organisms.
For a long time, it has been thought that genes form only as a result of the duplication of chromosomes, genome regions or single genes in protein-coding regions. It has been thought to be unlikely in non-coding genomic regions. By now, we have found that most genes are indeed created by duplication, but also in regions that do not code proteins.
In certain organisms, new genes may be formed also by horizontal gene transfer, wherein the genetic material of one species is transferred to an organism of another species. This phenomenon is mostly common in bacteria, and therefore, they have acquired several useful genes over time, some of which have also come from viruses.
It has been long known that bacteriophages, i.e., viruses that infect bacteria, have the ability to take the genes of bacteria from one cell to another, and thus, this ability is also being utilised in the methods of molecular biology. Sometimes the viral gene turns out to be so useful for the bacterium that it becomes an integral part of the bacterial genome. This phenomenon had not been expected to occur in eukaryotic organisms, including humans. The horizontal gene transfer from RNA viruses to eukaryotes had been considered especially unlikely.
Therefore, it was only quite recently discovered that this phenomenon has occurred in mammals on several occasions. “By today, it is clear that the event, which until recently had been thought impossible, has not been that rare after all, and gene transfers from RNA viruses to eukaryotes have taken place at least dozens of times in the last few tens of millions of years. At first glance, the genes transferred from viruses to mammals can have quite unexpected functions – for example, one gene transferred from a virus to humans is very important in the development of the placenta,” explained Aare Abroi, a senior research fellow in virology at the University of Tartu’s Institute of Technology.
It is difficult to study the evolutionary history of viruses because unlike many living organisms, they do not leave geological fossils. The genes transferred from a virus to the host a long time ago are in a way molecular fossils, which help us understand the history of viruses. However, research is complicated by the fact that we need to look back tens or even hundreds of millions of years. The relatively recent virus-to-host gene transfers are easy to identify by comparing pairs of genetic or protein sequences, but due to the fast evolution of viruses, genes with the same precursor may, over time, lose their reliable sequence similarities.
A doctoral student of bioinformatics at the University of Tartu, Heleri Kirsip, and a senior research fellow, Aare Abroi, applied a method for studying viruses, which enables to avoid the deficiencies of current methods. They used the hidden Markov models (HMM), which for a long time have been used mainly in the field of statistics, but for the first time by the scientists from Tartu also for studying viruses. “The primary limitation with previous methods was the inadequate identification of the more distant relatives – upon visual inspection, it is not easy to see how humans and seals could be related, but the relation becomes obvious when comparing their skeletons. The applied method does something similar, i.e., it enables to study a characteristic that is quite stable in time, the so-called protein skeleton, which cannot be seen with a simple visual inspection,” commented Abroi.
By using this novel method, it was discovered that a gene of an RNA virus infecting plants was integrated into the genome of insects between about 70 and 110 million years ago and has been fixed there, but what is more, this new knowledge confirms the effectiveness of the method. Furthermore, the approach described in Kirsip’s and Abroi’s research increases the time-related depth of gene transfer research two to five times and is significantly more precise and sensitive.
The work of the scientists opens up new possibilities for studying gene transfer from a virus to a host and vice versa. The method allows us to study the long-term coexistence and interaction between viruses and hosts, and also more thoroughly explain the evolution of viruses, and assess their age and role in global evolution. According to Abroi, the extent of genetic transfer allows us to conclude that gene transfer is also occurring today. Therefore, the senior research fellow finds that when studying the human genome, especially in personalised medicine, it should also be taken into account that the patient’s genome may contain genetic material from viruses and this may cause certain physiological characteristics.
Viruses are typically thought of as pathogens. However, studying viruses is important as they are the most abundant, genetically diverse and widely spread biological objects on our planet, which is why they play a significant role in the whole biosphere. There are about ten times more bacterial cells in the human organism than human cells, and the number of viral cells is even an order of greater magnitude. That is why it is important to understand the different roles of viruses in the biosphere as well as in the well-being and pathology of a human being. The senior researcher believes that society’s attitude towards viruses is going to change soon:
“About 30 years ago, bacteria were also seen negatively, fearing that they would only cause problems and diseases, and thinking they should be destroyed from everywhere at any cost (a good example are the antibacterial soap campaigns). Today, we know how necessary bacteria are to the human organism in the intestinal tract as well as on the skin, not to mention to the ecosystem. Excessive cleanliness causes several allergies and the lack of the right bacteria causes food intolerances and other problems. The same change in our knowledge and attitude is to be expected with viruses – even though viruses will remain to be parasites, they are not always pathogens but an important part of the ecosystem surrounding us.”
Read more about viruses and their genetics in the article "Protein Structure-Guided Hidden Markov Models (HMMs) as A Powerful Method in the Detection of Ancestral Endogenous Viral Elements" published in Viruses.
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