Season 3, Episode 11: Bloodless
When Enuka's nephew, Billy, is found dead near his home in Texas, her sister, Billy's mom Jamilla, is accused of killing him. Jamilla insists, however, that Billy was dragged off by a mythical creature: the "river cat". When Enuka and the rest of the NorBAC team investigate, they find evidence to suggest that Billy was killed by a cheetah that was mutated to contain genes from a prehistoric cat. Back in Toronto, Bob's visits to the hyperbaric chamber finally pay off as they seem to trigger the departure of the herpes viral DNA from his genome.
 Image provided courtesy of Shaftesbury Films. |
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Enuka consoles her sister, Jamilla. |
IS IT POSSIBLE TO ADD DNA FROM A PREHISTORIC CAT TO THE CHEETAH GENOME?
How much is known about the cheetah's ancestors?
The closest living relative to the African cheetah (Acinonyx jubatus) is the North American puma (Puma concolor). Both species evolved from a common ancestor about five to eight million years ago. There used to be cheetahs all over the world, but after a mass extinction ten thousand years ago killed off about 80% of existing vertebrates, the North American cheetah disappeared. DNA analysis of recovered specimens of these prehistoric North American cheetahs showed that it was very similar to the puma, and related to the African cheetah.
What is genetic diversity?
Within any species, there is some variation in genetic material. This is what makes individuals within a species unique. It's also a prerequisite for survival of a species: if, for example, a disease breaks out, it might kill many individuals within a species but the more resistant animals will survive. However, if all individual animals within a species have the same versions of all of the genes that affect their response to the disease, they might all succumb to the disease and die. A species as a whole is stronger if it is more genetically diverse.
Compared to other species, the genetic diversity in cheetahs is extremely low: their genes are all very alike. Currently, cheetah conservation programs are trying to breed cheetahs in captivity with other cheetahs that are as different as possible in an attempt to bring back some genetic diversity to the species.
What is mitochondrial DNA?
When we talk about DNA, we usually refer to DNA that is found in the cell nucleus. While the nucleus is responsible for storing and copying genetic information, other compartments of the cell carry out their own important tasks. The mitochondrion is one such cell compartment: its role is to produce energy for the cell.
Mitochondria are believed to have originated from a bacterium that got incorporated into the cells of higher organisms as they developed, more than a billion years ago. Why? Partly because mitochondria have their own genetic material: mitochondrial DNA.
 Image provided courtesy of Shaftesbury Films. |
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Enuka, Carlos and Mayko find puma-like DNA in the mysterious animal's tooth. |
In this episode, the coroner found animal hairs under Billy's finger nails. From these hair samples, mitochondrial DNA was collected and analyzed; the results suggested that the hairs came from an ordinary cheetah. But when Carlos and Mayko examined the marrow from the animal's tooth, they found puma-like DNA! So why was puma-like DNA not found in the mitochondrial DNA from the hair samples? Because techniques used to mutate an organism's DNA - for example, to switch off or remove a gene or to add a gene - are all carried out on nuclear DNA, not mitochondrial DNA. So the animal that killed Billy would still have normal cheetah mitochondrial DNA even if its nuclear genome had been altered by adding in prehistoric genes.
What are transgenic animals?
Transgenic animals contain genes from another organism, which are processed as if they were part of the animal's own genome. Scientists have successfully created various types of transgenic animals, but transgenic mice are most common. These animals are used in research; for example, to study diseases such as breast cancer or Alzheimer's disease.
Transgenic mice and the mouse genome are so well-studied that it's possible to control where the additional gene - the transgene - is added to the mouse's genome, and where and when in the body it is expressed. However, for other animals, these techniques aren't yet as advanced, and in many cases there is very little control over where an inserted gene ends up in the genome. It could end up in a harmless spot, or it might insert in such a way that it would interrupt and shut down an existing gene. This makes it very difficult to add more than one gene and still produce a healthy, full-grown transgenic animal.
Transgenic cheetahs have never been made, but if we assume that the cheetah studied in this episode only had one gene added, it's very unlikely that the NorBAC team would have noticed this. They would have looked at random parts of the DNA isolated from the tooth, and seen that it matched cheetah DNA. Picking up one additional gene would be highly unlikely. On top of that, neither the cheetah nor the puma have had their entire genome sequenced, so most of the animal's DNA (both cheetah and anything "puma-like") would not be found in a database search.
So?
It's extremely unlikely that anyone would have had access to prehistoric cat DNA and added it into the cheetah genome. While it's technically possible to add foreign genes to an animal's DNA, it would be very difficult to add more than one gene to the genome, and only a single gene would probably not be detected when the animal's DNA was compared to a database using modern methods.
DID YOU KNOW?
In this episode, the herpes viral DNA that has integrated into Bob's genome pops out again after Bob's visits to the hyperbaric chamber. David thinks this is caused by increased oxidative stress.
 Image provided courtesy of Shaftesbury Films. |
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Bob undergoing treatment in a hyperbaric chamber. |
Oxidative stress is characterized by an abundance of chemicals called "reactive oxygen species" or ROS. Small amounts of ROS are formed as a byproduct of the mitochondria's energy-producing reactions, but the cell is able to remove these small amounts. When the ROS levels increase dramatically, the cell can't remove them anymore, and the chemicals cause DNA damage, among other things. However, this type of DNA damage is not focused to any particular region of the DNA. It's unlikely that this would specifically remove inserted viral DNA. That being said, there are other techniques being developed that can specifically remove integrated viral DNA from genomic DNA using enzymes that recognize the viral DNA. This method is being studied as a possible step in the treatment of HIV infection, where the HIV virus integrates into the genome.
-- Eva Amsen
Want to read and learn more?
Read what the Cheetah Conservation Fund has to say about genetic diversity in cheetahs:
http://www.cheetah.org/?nd=41
Find out more about DNA extraction from woolly mammoth hair shaft samples:
http://www.sciencedaily.com/releases/2007/09/070927141921.htm
To learn how transgenic animals are made, visit this site that explains how it's done in mice:
http://genome.wellcome.ac.uk/doc_WTD021044.html
Read about oxidative stress:
http://en.wikipedia.org/wiki/Oxidative_stress
Learn how enzymes may be able to remove viral DNA from the genome:
http://www.rsc.org/chemistryworld/News/2007/June/29060701.asp
