Fine Read­ing: En­doge­nous Retro­viruses

by Elio

I can't think of any­thing more star­tling, more promis­ing, and more in­tractable in bi­ol­ogy than the busi­ness of en­doge­nous retro­viruses. They seem to be ubiq­ui­tous in both in­ver­te­brates and ver­te­brates, and even in plants. In hu­mans, they make up at least 8% of the genome, plus some bits and pieces. They are an­cient; in our lin­eage they go back per­haps 100 mil­lion years. Let's face it, if we hadn't been told about them, we could never have con­jured up such a strange story. It's like hear­ing that you pos­sess a limb or an or­gan that you didn't know about.

The very ex­is­tence of en­doge­nous retro­viruses (ERVs) touches us in a num­ber of ways. How is evo­lu­tion shaped by the ac­qui­si­tion of such vi­ral pack­ets of genes? How of­ten has it hap­pened? Did it arise by in­fec­tion, as seems likely? Is this an on­go­ing process that leads to fur­ther evo­lu­tion? What does this have to do with the evo­lu­tion of viruses? What does it re­veal about the reg­u­la­tion of gene ex­pres­sion? On bal­ance, do they do more good or more harm? All these ques­tions have arisen else­where, but they are brought to the fore by these strange en­ti­ties.

In­te­gra­tion of vi­ral DNA into host genome. Source

There is much to be learned, but cer­tain facts stand out. A strik­ing ex­am­ple of the good ERVs have done is seen in the case of the syn­cytin gene, whose prod­uct is in­volved in some es­sen­tial way in the de­vel­op­ment of the pla­centa. It is thought that ERVs may also play a role in the im­muno­sup­pres­sion needed to avoid fe­tal re­jec­tion by the mother. On the other hand, can they cause can­cer? With some lab­o­ra­tory-in­duced ex­cep­tions, ERVs have not been found in tu­mors. On the other hand, ERVs in hu­mans and great apes con­trol the for­ma­tion of a pro­tein (GTAp63) that pro­tects the germ line from can­cers. In ad­di­tion, ERVs may con­tribute to re­sis­tance to ex­oge­nous retro­viruses. So much for viruses be­ing "bad."

It fol­lows that know­ing about en­doge­nous retro­viruses should be part of the ed­u­ca­tion of all bi­ol­o­gists, not just retro­vi­rol­o­gists. I rec­om­mend a re­view by Jonathan Stoye en­ti­tled Stud­ies of En­doge­nous Retro­viruses Re­veal a Con­tin­u­ing Evo­lu­tion­ary Saga. Here you will find a clearly writ­ten ac­count of ERV ge­nomic ar­chi­tec­ture, re­pro­duc­tive cy­cle, and phy­logeny. Also dis­cussed are some of the con­se­quences of their pres­ence, in­clud­ing the ex­pres­sion of vi­ral pro­teins, the con­trol of host processes by ERVs, and their cost-ben­e­fit bal­ance. The com­plex sub­ject of con­trol­ling retro­vi­ral repli­ca­tion is ex­plained with clar­ity, as is the evo­lu­tion­ary in­ter­play be­tween the ERVs and their host. You might as well start some­where, and this is a good place for it.