Can viruses interfere with our genome?

Some very sur­pris­ing work sug­gests that vir­uses may have played a major role in evol­u­tion. Not only by for­cing their host to trans­form itself to pro­tect it, but by act­ing dir­ectly on the sequence of gen­omes. A story of hori­zont­al genetics.

In the nat­ur­al world, the shar­ing of genet­ic mater­i­al does not always take place from par­ent to child… Genet­i­cists refer to any mech­an­ism of DNA trans­mis­sion oth­er than repro­duc­tion as ‘hori­zont­al trans­fers’¹. This is a well-known phe­nomen­on in bac­teria or archaea (proka­ryot­ic microor­gan­isms²). It explains, among oth­er things, the acquis­i­tion of res­ist­ance to anti­bi­ot­ics that causes so many prob­lems in pub­lic health. Bac­teria exchange genes, via small cir­cu­lar pieces of DNA called plas­mids, which allow them to adapt quickly to new envir­on­ment­al con­di­tions, such as the pres­ence of an anti­bi­ot­ic molecule. But can multi-cel­lu­lar organ­isms, even very com­plex ones like ver­teb­rates, also exchange genes by hori­zont­al trans­fer? This is the ques­tion I am exploring…

In euk­a­ryotes³, stud­ies com­par­ing the gen­omes of dif­fer­ent spe­cies have shown that the phe­nomen­on is rare, but not impossible. Hori­zont­al trans­fers are easy to find, because they res­ult in a high degree of sequence sim­il­ar­ity between two spe­cies that are very far apart on the tree of life. They are too far apart, in evol­u­tion­ary terms, for the sequence sim­il­ar­ity to be explained by a com­mon ancest­or through the generations.

Many of the cases described involve insects, often with genet­ic mater­i­al from bac­teria. For example, beetles have a gene from bac­teria that helps them digest the pep­tide wall of plants. Oth­er sequences facil­it­ate the break­down of tox­ic com­pounds released by plants to pro­tect them­selves. The tobacco white­fly, a small white­fly cap­able of dev­ast­at­ing crops, has acquired an enzyme through hori­zont­al trans­fer that allows it to pro­tect itself from tox­ic phen­ols emit­ted by plants, as recently demon­strated by Chinese and Swiss col­leagues⁴. This time, it is not a bac­teri­um that has delivered the genet­ic solu­tion, but a plant… It appears to be a trans­fer between two euk­a­ryot­ic organ­isms, which raises the ques­tion of the under­ly­ing mechanism.

Intriguingly, the phe­nomen­on has also been doc­u­mented between two ver­teb­rates. Atlantic her­ring and two spe­cies of smelt share an anti­freeze pro­tein acquired by hori­zont­al trans­fer⁵. This is a unique example between ver­teb­rates. But if we con­sider not only genes, but all gen­ome sequences, the phe­nomen­on does not seem quite so rare.

In the­ory, to carry out a hori­zont­al trans­fer of genet­ic mater­i­al between two ver­teb­rate spe­cies sev­er­al con­di­tions must be met. It requires a mobile sequence from the donor spe­cies, a vec­tor to trans­port it and the pos­sib­il­ity of insert­ing itself per­man­ently into the gen­ome of the recip­i­ent spe­cies, i.e., into its germ line, so that it can be trans­mit­ted to the des­cend­ants of the recip­i­ent individual.

Let us con­sider the first two points: the prob­lems of donor sequences and the vec­tor. In addi­tion to genes, there are “mobile” or “formerly mobile” sequences in gen­omes. They make up a very large part of the sequences of ver­teb­rate gen­omes – more than 50% of the human gen­ome is derived from such sequences – these are the trans­pos­able ele­ments. These are non-cod­ing DNA, cap­able of mov­ing and mul­tiply­ing in the gen­ome. Most of them are now inact­ive, i.e. unable to move, but their prop­er­ties make them prime can­did­ates for par­ti­cip­at­ing in hori­zont­al transfers. 

By study­ing the gen­omes of 200 insect spe­cies and 300 ver­teb­rate gen­omes, we have revealed more than 2,000 hori­zont­al trans­fers of trans­pos­able ele­ments between insects and more than 900 between ver­teb­rates⁶⁷. For the lat­ter, most of the hori­zont­al trans­fers con­cern fish, which sug­gests that cer­tain aspects of their life­style, such as the aquat­ic envir­on­ment or the extern­al fer­til­isa­tion of eggs, could be more favour­able to the phenomenon.

In addi­tion, small organ­isms are known to carry genet­ic mater­i­al. These are vir­uses. We there­fore ima­gined that they could be poten­tial vec­tors for hori­zont­al trans­fers. Ana­lys­is of 11 dif­fer­ent vir­uses infect­ing cells in cul­ture or labor­at­ory anim­als shows that some can pick up trans­pos­able ele­ments from their host⁸. Not all were cap­able of doing so. Vir­uses spe­cial­ising in human and rodent infec­tions showed no trans­pos­able ele­ment sequences from the human or rat gen­omes. In con­trast, vir­uses from flies and but­ter­flies do have such sequences: between 0.1% and 26% of the vir­us particles ana­lysed (on aver­age 5%) had trans­pos­able ele­ments from their host.

But the demon­stra­tion is not fin­ished. To com­plete the hori­zont­al trans­fer, these vir­uses must be able to give the trans­pos­able ele­ment acquired in the host to anoth­er recip­i­ent host. We are cur­rently eval­u­at­ing this ques­tion in a but­ter­fly spe­cies. We hope to be able to observe how trans­pos­able ele­ments evolve by jump­ing from one spe­cies to another.

If our hypo­thes­is is cor­rect, we will have uncovered an import­ant mech­an­ism in the evol­u­tion of spe­cies. By allow­ing the trans­mis­sion of genet­ic mater­i­al out­side of repro­duc­tion, vir­uses would be harm­ful. They would have con­trib­uted to the diversity of gen­omes. We are there­fore explor­ing a whole aspect of genet­ic evolution.

Interview by Agnès Vernet