Aug 26

Aug 26 Making new genes or stealing them?

HIV viral life cycle. David S. Goodsell, The Scripps Research Institute. Attribution 4.0 International (CC BY 4.0)

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This is a podcast called Genetics Unzipped, so unsurprisingly, we spend a lot of time talking about genes. These are stretches of DNA or RNA that encode the instructions that tell cells to make specific proteins. Just to be pedantic, there are also genes that make functional non-coding RNAs, which don’t encode a protein but instead have their own job to do in cells.

As far as we can tell, all of life on earth evolved from one common ancestor, LUCA, which must have had one set of genes, whatever they looked like. But that leaves the question of how this simple set of genes diversified to encompass the incredible diversity of genes that now exist in trillions of extant and extinct species on earth. In other words: where do genes come from?

Some new genes form when nature tinkers with existing ones by accidentally changing, duplicating, blending or breaking them up. Small changes in some powerful genes can make them a major source of evolutionary change. For example, changes in HOX genes that help lay out complex organisms’ body shape, telling your body ‘make a head here’, ‘make feet here’ can have enormous consequences for the resulting organism.

HOX genes are often arranged in clusters thought to have formed when a single original HOX gene was duplicated. For example, humans have 39 HOX genes in 4 clusters. That’s a lot of accidental copying and pasting. We talked about this more back in episode 3 of our previous series, Fish, Facts and Fiction.

Other genes have even weirder origins, with the latest science showing that some of our genes come from our mortal enemies - viruses.

Throughout evolution, our ancestors have been locked in a war against invading viruses. These tiny molecular machines consist of little more than a string of genetic material in a protein coat, invading our cells and hijacking their machinery to create millions of copies of themselves, sometimes at the expense of our lives.

Some viruses, such as HIV, are retroviruses, meaning that they can insert themselves into our DNA, where they get copied and pasted into multiple parts of the genome. During the course of evolution, these inserted viral genes can jump around, mutate and change, eventually becoming embedded in their host's genome. As a result, scientists think that around half of our genome contains DNA sequences that have been abandoned by ancient viruses, adding up to a whole lotta genetic junk.

But sometimes, as it turns out, organisms have harnessed these viral invaders and put them to work for their advantage.

For example, syncytin genes, which make proteins that help form the placenta during pregnancy and stops the mother’s immune system from attacking her baby in the womb look suspiciously like genes from a retrovirus – which are often masters at evading attack from the immune system.

Curiously, the syncytin gene is only found in humans and large primates, suggesting that somewhere in our evolutionary timeline, before humans and primates split, we stole these viral genes and turned them to our own ends. Interestingly, some mammals - including mice, cats and dogs- have syncytin genes that do the same jobs but look like different viruses, suggesting that other sections of the evolutionary tree employed the same tactic but using different viruses.

Other stolen viral genes help us defeat viruses themselves. For example, a gene in the human genome that switches on immune defence mechanisms when it detects a viral infection, forcing infected cells to self-destruct, has been traced back to a retrovirus from 45 to 60 million years ago

The viruses trapped in our genomes have bought us enormous benefits, but unfortunately, it isn’t all good news. The ability of viral genes to jump around our genome can deactivate essential genes and cause disease. Experts suggest that a new jump occurs in around 1 in 20 babies, which can be harmless or - just as easily - disease-causing or even deadly, depending on the genetic changes resulting from the jump.

Jumping genes have also been linked to the genetic chaos inside cancer cells and other conditions like schizophrenia, epilepsy, and intellectual disabilities. What’s more, it turns out that stealing genes is a two-way street, with recent analyses showing that pathogens like influenza can snatch genetic sequences from their hosts and use them for their own sneaky devices. Unfortunately, it seems to be hard to keep our genes to ourselves!