Publish at December 03 2020 Updated November 21 2024
Your DNA is an open book that tells more about your ancestors than it does about you, in which each of them has left a trace, a mutation or a mark of what they experienced, representing a new fork in the genetic tree of the human species that you carry and will pass on to your descendants.
Human genetic information is made up of 30,000 genes, which is hardly more than that of the c. elegans flatworm, the drosophila fly or the mouse. Protein-coding genes account for just 2% of total DNA, while 98% is non-coding and 50% is viral DNA.
Just breathe! All is well! You're still the same person, which doesn't make you more viral than human. Rest assured, no one is trying to develop a vaccine against humanity.
These mostly inactive viral remnants are the result of horizontal genetic transfer, whereby an organism receives genetic material from another organism, in this case a virus, and integrates it permanently into its genetic heritage. A fraction of these elements remain mobile and constitute Transposable Elements (TEs). These TEs can copy and paste themselves and move within the DNA, sometimes taking a gene or regulatory element with them, thus contributing to the plasticity of their host's genome. Mobile elements have played a major role in the evolution of many species, and continue to do so today.
In his thesis "Étude de transferts horizontaux de matériel génétique entre virus et animaux" (Study of horizontal transfers of genetic material between viruses and animals), Vincent Loiseau deals with the fascinating subject of horizontal transfers of genetic material, in the form of a compilation of commented scientific publications.
The aim of this thesis was to dissect the process by which viruses act as DNA vectors between different hosts. To do this, the student broke down and explored this problem from different angles:
The central subject of this thesis shatters a paradigm of biology that many students still believe to be true: the vertical transmission of genetic information. This thesis is part of a body of literature that is gradually breaking down this dogma, highlighting the infinite complexity of the living world.
The author's narrative draws us into the logical unfolding of his thoughts, in which we share the excitement of hypothesis formulation, the hazards of method, the eroticism of a plausible solution, and the rational critical sense in the face of the latter, which interweaves failure, disillusionment and hope.
The author reminds us all that research is punctuated by failures, and emphasizes that an experimental failure remains a result that in no way justifies closing the parenthesis on a project, but on the contrary, shows imagination in going beyond the challenges encountered.
"Several thousand such horizontal transfers of ETs have been identified, whereas only one example of horizontal transfer of a non-ET gene between animals [an antifreeze protein shared between various fish species] has been described to date.
ETs are selfish mobile genetic elements, capable of moving and duplicating themselves within genomes. They are generally classified into two categories:
- class I ETs, or retrotransposons, which transpose by a copy/paste mechanism via an RNA intermediate; and
- class II transposons, or DNA transposons, which transpose by a cut-and-paste mechanism via a DNA intermediate.
Because of the numerous repeated sequences of ETs in genomes, their study has proved and continues to prove complicated, as they interfere with the assembly of good-quality genomes. Although the number of copies in metazoan genomes varies, virtually all eukaryotes are considered to carry ETs in their genomes.
Examples include the human genome, which is estimated to contain around 50% of ETs, and the maize genome, which is over 85% ETs. ETs are thus part of the non-genic repeated DNA of genomes, and have long been perceived as useless. Moreover, waves of ET transposition in genomes often result in deleterious mutations, negatively impacting host selective value.
Today, this view is tending to be nuanced as studies show that these sequences can shape host genomes and influence the evolution of organisms, being a source of mutations, genetic polymorphism, chromosomal rearrangements and participating in the regulation of gene networks."
The results did not reveal either an expression pattern or a general increase in overall ET expression induced by viral infection. Nevertheless, some ETs appear to be overexpressed and transcribed in conjunction with the virus during certain infections. This seems to indicate that some ETs from the host under study have transposed and been transcribed from the viral genome, allowing integration in a second infected host.
The student remains cautious about his conclusions, however, due to a sequencing methodological limitation. At the open end of this section, he presents an elegant theory of how ETs are used by cells to sabotage viral replication as intracellular immune tools, giving the host immune system more time to deal with the infection.
Comparison of data on different virus-host systems shows different dynamics of ET insertion in viral genomes specific to each system. The average frequency of ET insertion in a virus observed by the student is less than 10%, with some viruses having frequencies in excess of 26%. The results obtained show that for some viruses, the quantity of ETs that can be integrated represents 25% of the final viral DNA. Thus, some virus-host systems appear to be favorable to transposition into viral genomes, while others are less so.
The researcher reports for the first time a case of transfer of mobile elements between two viruses of different species within the same host. This reinforces the supposed contribution of viruses as vectors of ETs, and explains the persistence of these ETs within them, constituting dynamic genomic ecosystems. In addition, the student highlights a family of viruses capable of infecting a wide variety of hosts, although no studies of horizontal transfer and frequency have yet been carried out on them.
This research work is the first to report in detail a case of interspecies horizontal transfer vectored by a murine Bxv1 retrovirus to the human Hep2-clone 2 B cell line. This virus-mediated horizontal transfer can be seen as the confirmation of two key steps: the acquisition of a piece of the host genome by a virus, followed by the integration of this genomic fragment into the genome of another host. Moreover, if this experiment is reproducible, it could provide an interesting molecular study model for future research.
This thesis shows the unity of life on earth, sharing a common code of information which is DNA. It also shows that our evolution is not only the result of simple random mutation of ancestral information inherited from a common ancestor, but also of horizontal transfers vectored in part by viruses.
In a world where GMOs are demonized as unnatural by some sections of public opinion, what are we to make of these natural processes of copy/paste and intra- and inter-species genetic editing? In other words, what is natural in the context of genetic modification?
Gentlemen, if your child is more like your best friend, your neighbor or your letter carrier, don't necessarily question your partner's fidelity. It could just be a bad viral joke.
Vincent Loiseau. Study of horizontal transfers of genetic material between viruses and animals.
Evolution [q-bio.PE]. Université Paris-Saclay, 2020. French. ⟨NNT : 2020UPASL018⟩.⟨tel-02983223⟩
Link to thesis open archive: https: //tel.archives-ouvertes.fr/tel-02983223
Link to thesis PDF: https://tel.archives-ouvertes.fr/tel-02983223/document
Link to the research team associated with this thesis: http: //www.egce.cnrs-gif.fr/?page_id=4003
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