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Can viruses interfere with our genome?

Clément Gilbert
Clément Gilbert
CNRS Research Fellow in Genetics at Université Paris-Saclay
Key takeaways
  • Horizontal genetic transfer is the phenomenon by which genetic material is transmitted from one external organism to another, without the latter being a descendant.
  • These transfers lead to strong sequence similarities between two species that are too far apart in the tree of life for the similarity to be explained by a common ancestor.
  • By studying the genomes of 200 insect species and 300 vertebrate genomes, the researchers revealed more than 2,000 horizontal transfers of transposable elements between insects and more than 900 between vertebrates.
  • Viruses are small organisms known to carry genetic material. They could therefore be potential vectors for horizontal transfers.
  • If their hypothesis is confirmed, they will have uncovered an important mechanism in the evolution of species.

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.

A remarkable rarity

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.

On the viral trail

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
1R. Acuña et al., PNAS 2012 109 (11) 4197–4202 ; DOI : 10.1073/pnas.1121190109
2A sin­gle-celled organ­ism with free DNA in the cell
3Organ­isms whose DNA is enclosed in a nucle­us, and which can be mul­ti­cel­lu­lar
4J. Xia et al., Cell 2021, 7, P1693-1705.e17. DOI : 10.1016/j.cell.2021.02.014
5LA Gra­ham, PL Davies, Trends in Genet­ics 2021, 6, P501-503, June 01, 2021. DOI : 10.1016/j.tig.2021.02.006
6J. Pec­coud et al., PNAS 2017, 114 (18) 4721–4726 DOI:10.1073/pnas.1621178114
7HH Zhang et al., Nat. Com­mun. 2020, 11, 1362. DOI : 10.1038/s41467-020–15149‑4
8V. Loiseau et al., Mol Biol Evol 2021, 38, 3512–3530. DOI :. Error! Hyper­link ref­er­ence not valid.10.1093/molbev/msab198

Contributors

Clément Gilbert

Clément Gilbert

CNRS Research Fellow in Genetics at Université Paris-Saclay

Clément Gilbert is a CNRS Research Fellow at the Evolution, Genomes, Behaviour, Ecology (EGCE) laboratory (UMR 9191 CNRS/Université Paris-Saclay). His research focuses on horizontal transfers of genetic material between species. He seeks to quantify these transfers using comparative genomics approaches, and to characterise the biotic and abiotic factors that influence their distribution in the phylogeny of eukaryotes. His work also aims to elucidate the molecular mechanisms involved in horizontal transfers, in particular by studying the role of certain viruses as vectors in these transfers.