My genome is full of parasites. Please help


(Stephen Matheson) #1

The average human genome consists of many millions of defunct retroviral elements and even more copies of mobile elements called transposable elements (TEs). These are virus-like pieces of DNA that can move about in genomes. Since the initial completion of the Human Genome Project, these elements have been estimated to comprise at least half of a typical human genome, but more recent analysis puts the proportion closer to 2/3.

This fact about the human genome is well known to biologists but carefully ignored by those purveying a picture of the human genome as an exemplar of “design.” But we know a lot about the consequences of carrying these TEs around in our genomes. They can come back to life, as mobile genetic elements, and wreak havoc. In fact, mammalian cells deploy an arsenal of tools to struggle against this. When/if these systems are inactivated, lots of bad things happen, most notably the disruption of the structural integrity of the genome itself. The study of damaging effects of TEs in human cells is strong and ongoing, and now there’s a new report that implicates TEs in aging.

We already knew that TEs increase during aging, at least in cells, which suggested that aging could be either a cause or a consequence (or both) of the partial unleashing of these things. Now we have some direct evidence for this, and an explanation for what’s going.

The basic summary is that a phenomenon associated with aging, called senescence, triggers a collection of problematic responses called SASP (senescence-associated secretory phenotype, if you must know), in some cells in the body. The new work shows that this response includes the sudden and dramatic liberation of a specific human TE called LINE-1. Interfering with these LINE-1 elements can protect cells (and animals) from age-related health decline.

In other words, the mobile elements in our genomes, which are DNA parasites operating on huge scales and using specific strategies to propagate themselves and which account for as much as 2/3 of our total DNA payload, are potentially a big reason for loss of health in aging.

Can “design” explain this? Yes, if by “design” you include the machinations of DNA parasites.

News article about the new paper:

https://www.nature.com/articles/d41586-018-07553-0

As always, I’m happy to send a PDF to anyone who asks.


Reaping the Whirlwind: protein function without stable structure
(Jay Johnson) #2

Thanks for the update and excellent summary. I would ask for the paper, but the news article already verges upon “over my head.” I loved the fact that there were two footnotes within the first three words, references to “old” and “diseased,” in case I didn’t know what those words meant. (Turns out, I didn’t.)

In the end, the article answered the main question that kept coming into my head, which was whether these drugs might screw up the immune system. Here’s the reply: “Encouragingly, lamivudine has been used in humans as a long-term antiretroviral therapy without major side effects — unlike other senomorphic compounds such as rapamycin, which blunts the SASP but is a potent immunosuppressant. However, there are as yet no reports that lamivudine improves the healthy human lifespan or any indications that it represses retrotransposons in humans.”

I do have a couple of questions about transposable elements. Do we know how these got into our genome? Are they “leftovers” from ancient viral infections? I really wasn’t clear on this point. Also, do TEs have anything to do with the “modular” nature of the great ape genome and the concept of structural variation? This was mentioned in the recent Nature article that you shared with us about the assembly of their genomes.


(Stephen Matheson) #3

Those are great questions. The endogenous retroelements (LINE1, or L1, is the most famous in the human genome) are not clearly traceable to viruses from the outside, at least not as far as I know. They have similar machinery to retroviruses, but I think there is a fascinating chicken-and-egg question there, since it could be that the elements first arose inside cells and then went rogue as viruses. I’m not sure what the current thinking is, and it probably depends on which retroelement is under discussion. L1, for example, is ancient and ubiquitous in vertebrates, so it “got into our genome” half a billion years ago.

We do know that TEs can induce genomic instability, which can lead to structural variation, so yes for sure. I don’t think we know much about the extent to which TEs contribute to structural variation within great apes.


(Jay Johnson) #4

That in itself says volumes.


(system) closed #5

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