#transposable elements

Switched Off

Hidden within our genome are sequences of DNA called transposable elements (TEs) that can move between locations, and potentially disrupt key genes. Our germ cells – precursors of eggs and sperm – have evolved a defence in the form of piwi-interacting RNAs (piRNAs), which silence TEs. But whether piRNAs also silence genes involved in producing germ cells was unclear. Using the nematode worm as a model, researchers found that piRNAs silenced genes involved in sperm formation. In worms with mutated non-functioning piRNAs (bottom), there were more germ cells expressing genes linked to creating sperm (red) compared to a ‘normal’ worm (top). As these worms are hermaphrodites, they need this ‘switch off’ of sperm production to be able to start making egg cells (yellow). This study shows that piRNAs could have wider roles in humans beyond simply silencing TEs.

Written by Sophie Arthur

Image from work by Eric Cornes and colleagues

Mechanisms of Epigenetic Inheritance, Department of Developmental and Stem Cell Biology, Institut Pasteur, UMR 3738, CNRS, Paris, France

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Developmental Cell, January 2022

I’ve talked before the research done in my lab here, but I haven’t talked about my personal research interests. My of interest is, yes you read the title, transposons. What are transposons though? Transposons, or transposable elements, are bits of genetic code that is transposable (hence the name). In essence, I, you, and nearly every organism that has ever existed has bits of DNA in them that will jump around at random. One minute you could have DNA in spot A in chromosome 1, and the next day it will be in spot Q in chromosome 12. This is the nature of a transposable element.

Transposons were discovered in the late 40s by Barbara Mcclintock while experimenting with maize with broken chromosomes who had noticed that some leaves had unusual color patterns. She hypothesized that these were due to certain parts of the gene breaking in some cells and being added to other cells during cell division. This turned out to be false after she had observed that parts of chromosomes had switched places. The fact that DNA could move was so groundbreaking that she was largely ignored for 20 years. However, her work was fortunately rediscovered when transposable elements were discovered in bacteria in the late 70s. And in 1983 she won a Nobel prize for Physiology or Medicine, so the waiting game did pay off eventually.

Today we know transposable elements are in nearly every organism, from the lowly starfish to the mighty echidna, and everything else with DNA. Why and how they came to exist is anyone’s guess. It’s possible that one transposon developed in the first organism and spread, or it occurs multiple times separately. We don’t have DNA samples from the dawn of life, which makes answering this question very hard. Another curiosity of the transposon is how similar it operates to a retrovirus. A retrovirus inserts its own DNA to a host cell’s DNA (like a transposon) to trick the host into producing more viruses (also like a transposon).

There are two classes of transposons, aptly named Class I and Class II, and both of these classes has to do with how they ‘jump’. Class I transposons (aka retrotransposons) move by being copied into DNA’s sister molecule, RNA. The RNA, now free from the chromosome, moves around until it is copied back into DNA. Like a bad neighbor, this DNA then takes the liberties of reinserting itself back into the DNA.

Class II transposons (aka DNA transposons) are much more direct. Instead of going through the messy process of being copied and converted multiple times, it just up and leaves the spot in the chromosome it’s located in and then enters a new area. What’s good (for the transposons anyway) is that most of the information needed to move is located within the transposon, meaning that as long as it doesn’t mutate it can keep up this seemingly random nomadic lifestyle.

Exit for Two

We all begin as one cell which divides into two – but for an embryo to advance further in development, a so-called jumping gene MERVL needs to be rapidly switched off. MERVL is known to be controlled by a factor called Dux, but how Dux is regulated and affects exit from the two-cell stage was unclear. Now, researchers have discovered that the cell’s nucleolus plays a role in regulating Dux. The nucleolus (pictured; DNA in cyan, nucleolus compartments in various colours) is part of our cell’s headquarters – the nucleus – and responsible for making our protein-making factories called ribosomes, and not commonly associated with gene regulation. By disrupting the nucleolus, Dux quickly re-activated, leading to increased levels of MERVL keeping the embryo stuck at the two-cell stage. Not only does embryonic exit from the two-cell stage require genes, like MERVL, to be switched off, the embryo also requires a functioning nucleolus to advance.

Written by Sophie Arthur

Image from work by Sheila Q. Xie and colleagues

Chromatin and Development Group, MRC London Institute of Medical Sciences, Imperial College London, London, UK

Image copyright held by the original authors

Research published in Genes & Development, March 2022

Remember that 86% of "junk" DNA we're carrying around? We're discovering new useful characteristics in it all the time, but a sizeable chunk - probably at least 40%  - is legitimate parasitic junk. Transposons are small DNA sequences prone to "jumping" around your genome, deleting themselves from one chromosome to appear in the middle of another.

The consequences of this jumping vary. If a transposon inserts itself in the middle of a functional gene and interrupts it, you might be in big trouble. Fortunately, you have two copies of every gene in your body, so in most cases you'll be okay even with a case of Rude Transposon. And don't forget, only 1% of your genome is dedicated to producing protein. Most of the time these transposons just swim around in other junk.

(Knock knock. Who's there. Interrupting transposon. Interrupting transpos - HI I'M HERE TO TAKE ADVANTAGE OF YOUR REPLICATION MACHINERY.)

Like anything that's been around throughout evolution, transposons may have been co-opted to perform actual genetic functions - sort of a "might as well use what we have" approach. These findings are still emerging, but some researchers have suggested cells use transposons to regulate gene expression. Others argue transposons form part of a cellular stress response.

Like any form of mutation, transposons also drive evolution. Their unpredictable nature contributes variation to our genomes, letting us cast a wider net in our genetic search for advantageous changes. One paper argues that transposons are responsible for rapid human evolution - in particular the unprecedented increase in brain size that gave us modern human brains. From the paper:

Evolution of the lineage leading to humans during the last several million years was striking. In this period the brain in our lineage tripled in mass... What we know is that the result was the modern human brain, which has been called the most complex thing in the universe.

Transposons are distinct from viruses because they do not code for proteins and they are not infectious. But they do bear minimal resemblance: both are genetic elements that rely on the transcription machinery of a host in order to propagate. Like viruses, transposons are not alive, but like living things, they exist because of their propensity to be replicated. Despite the detriment to their host genomes, they have not been eradicated by evolution. They might simply be too hard to catch as they jump everywhere. Or perhaps their contributions - providing variation to a population or services to a host cell - outweigh the risks of their presence.

Barbara McClintock by chid0 :