Monday, September 5, 2011
Chimeras unveiled: genetics versus epigenetics
You think you know everything about chimeras? Well, think again: today I'm about to surprise you.
Let's start from the very beginning: in Greek mythology the Chimera was a monster, part goat, part snake and part lion.
Like with many other things, genetics borrowed the term to define organisms that are the result of genetically different tissues fused together. This happens at conception, when two fertilized eggs fuse together to form a single individual. Conceptually, it's the exact opposite of identical twins, where one fertilized egg splits into two identical individuals. Chimeric animals, for example, will present bits of fur of different colors. A chimeric person may show different pigmentation across his or her body. The individual will have two distinct DNAs in different tissues.
I'm sure so far I haven't told you anything new.
One day one of our experimentalist collaborators called to tell us they'd found a chimera. He was quite excited about the discovery. I scratched my head. Because you see, he was talking about HIV. And the thing with HIV is that it has one molecule of RNA. Just one, that's all there is. And so, how can a virus be the result of "tissues" coming from different genomes?
It turns out the definition is slightly different for viruses. A chimeric virus is a virus that has bits of extraneous DNA in its genome. Here I should be careful: HIV is a retrovirus, which means a free viral particle carries RNA, not DNA; however, once it enters the cell, an enzyme called reverse transcriptase turns it into DNA and, as DNA, it enters the host cell's nucleus and gets integrated into the host's DNA. This integration is what allows the virus to replicate. It's also what caused our chimeric virus to integrate in its own genome part of the host's genome.
The concept is used in gene therapy: a retrovirus is basically a shell (called envelope) with genetic material inside, and it's designed to inject the genetic material into the cell's nucleus. This is a fundamental step in the retrovirus's life because without it, it can't replicate. Many gene therapy clinical trials have exploited this mechanism by genetically engineering a chimeric retrovirus that carries human genes. Once the virus enters the nucleus, it delivers the new genes, thus "fixing" the problematic ones. I will talk more about gene therapy in a future post.
So now you've met a new type of chimera. Wait, it's not over yet.
Remember when I introduced the concept of epigenetics? Remember what pseudogenes are? They are ancestral or redundant parts of our DNA that are usually non-coding. We learned in those earlier posts that epigenetic processes do change during one's lifetime, and, as a result, pseudogenes can be activated and become coding genes. They are called chimeric genes.
An individual with chimeric genes is what I call an epigenetic chimera. The individual has the same DNA across all of his or her tissues, but some cells express genes that are otherwise non-expressed in the species.
In summary, we have three types of genetic chimeras: individuals with different DNAs; viral particles integrating different bits of extraneous DNA; and individuals expressing different chimeric genes.
Now that you know the different types of genetic chimeras, you are ready to learn why you and I are chimeras, too.
Picture: Statue of Hutshepsut, Metropolitan Museum of Art, New York City. Canon 40D, focal length 85mm, shutter speed 1/10. Hutshepsut was a female pharaoh, often depicted in a masculine attire and with the typical pharaoh beard, symbol of pharaonic power.