Mutations in numerous pathways need to accumulate for cancer to progress. Given the ability of transposons to cause mutation and the role of mutation in cancer, it seemed likely that transposons would play a role in cancer. A few years ago, Iskow and colleagues showed that transposons jump in some lung tumors, suggesting a link to cancer progression. They also showed that methylation levels are often lower in lung cancers. Methylation is important for transposons silencing, so they hypothesized that lowered methylation in cancer could lead to more transposon jumps. This would “destabilize” the genome, allowing more mutations to accumulate, and accelerating cancer progression.

However, very little evidence of this connection existed until recently. With the advent of high-throughput sequencing, it is becoming possible to examine changes in the genomes of cancer cells. Lee and colleagues report on one such study. They decided to look at the effect of retrotransposons by comparing the location of these jumping genes in normal and cancer cells. Retrotransposons copy their sequence from one location to another by going through an RNA intermediate that is read “backwards” from RNA to DNA.

In their study, they had to overcome a problem: because transposons are found throughout the genome and are mostly the same in different individuals, it is hard to figure out exactly where new transposons are located. To sort this out, they developed a bioinformatics tool that could align sequence to a reference genome and identify new transposon sequence associated with this sequence. They then used normal tissue and cancer tissue from the same individual to identify transposition events in cancer cells.

Interestingly, different cancer types had different numbers of transposon jumps. Brain and blood cancers did not have many transposon-induced mutations, while epithelial cancers had frequent insertions. These jumping-gene insertions are probably important for cancer, as many of the insertions occur within genes known to affect cancer biology.

If these jumping genes cause mutations and promote cancer, why are they there? It’s still an area of contention, but all that jumping around helps provide diversity in our genomes. Sometimes that will prove to be bad, but it also allows natural selection to act on the diversity, allowing new, helpful innovations in our DNA power evolution.

Iskow el al, 2010. Natural mutagenesis of human genomes by endogenous retrotransposons. Cell. 141(7):1253-61.

Lee et. al, 2012. Landscape of Somatic Retrotransposition in Human Cancers. Science. 337(6097): 967-971.

Some students I was teaching thought that this might be possible: to engineer the insulin-producing cells with a correctly functioning gene, a type of gene therapy.  While this has been a goal for researchers, and they have successfully made insulin-producing cells in the lab from embryonic stem cells, they are not appropriate for transplant because they do not release the insulin in response to glucose levels.  Plus, the immune system might still recognize these cells as foreign and destroy them.

So a new study is looking at transforming cells of the gut that don’t have a specific job yet.  These cells receive signals throughout the life of an individual to become many different types of cells that are used for normal gut function.  So could they engineer these cells to receive the signals to become insulin-producing cells?  Also, would the cells only release the insulin in response to blood glucose levels?

Two Columbia University researchers have started finding possible answers to these questions.  Once they turned off a gene that normally plays a key role in the fate of a cell, insulin-producing cells were generated.  Having cells in the gut that make insulin can be dangerous if they did not release insulin in response to blood glucose levels, but these “new” gut cells have glucose-sensing receptors to allow them to do just that. Another remarkable feature was that the gene could be turned off either early on in development, or later on in adulthood, so it wouldn’t matter how old the patient was.

The next step is to take the research that has been done on mice so far, and see if they can mimic this in humans with the use of a drug or chemical.  This method will also need to prove to be safe and more effective than current methods of treatment, not just to avoid the burden of daily injections.

The timing of this internal clock is related to the amount of exposure to light.  How do circadian rhythms work in organisms that are not exposed to light?  A Somalian cavefish, Phreatichthys andruzzii, is a blind species that has been living without light for approximately 1.4 to 2.6 million years!

Researchers compared the cave fish to zebrafish during exposures to 12 hour period of light followed by 12 hour period of dark.  The cave fish remained active at irregular times while the zebrafish were active during exposure to light.  Also, it was identified that in the zebrafish, genes associated with circadian rhythms were activated from exposure to light while the same genes in the cavefish were not.

In addition to light, these rhythms can also respond to other factors, including food.  When scientists fed both types of fish at specific times for a month, they found that both fish were ready to eat at those times, demonstrating the circadian rhythms.  Also, the genes associated with the rhythms were activated in both fish.

Photoreceptors are cells with specialized proteins that respond to light.  While the genes associated with circadian rhythms in the cave fish were normal but not activated, it was found that genes for certain photoreceptors were mutated.  The mutation caused important sections of the photoreceptors to be missing.  After introducing functioning genes into cave fish, it appears that these transgenic fish could only respond to blue and green light.  This tells us that there are photoreceptors for light that we do not know about!

The cave fish offers scientists an opportunity to learn more about not only circadian rhythms, but also the mechanisms behind how we respond to various forms of stimuli. 

Protein is a broad category that includes enzymes and hormones. When you eat an apple, your body produces enzymes to break down that apple and build new products for your body. If you have a lot of glucose (a type of sugar) in your blood, the cells in your pancreas will read the gene for insulin and produce the protein. Even the tight skin of youth relates to proteins. The elasticity of your skin depends, in part, on the production of the protein collagen in your skin cells. As humans get older we produce less collagen, which is one of the reasons our skin becomes less taut.

If an organism has a change, or mutation, in their DNA what can this mean? If the mutation happens in a region of DNA that does not code for anything then the mutation may go unnoticed. If, however, the mutation happens in a coding region of a gene, then protein production may be affected. In some cases, the change in DNA can cause a protein to be produced that will have no function or even be destroyed by the cell. In contrast, the protein may be produced in larger amounts or at different times.

Another possibility is that the altered protein may be just slightly different. This new protein may be able to even carry out the same job of the original one. Also, the new protein may offer a new function or provide a new trait for the organism. All of these possibilities offer variety in life.

Although there is often a negative association with mutations because of their role in causing genetic disease, life would not exist without them.

In an August article from Scientific American, a rare genetic mutation has been identified on a gene called DEC2 that causes it’s carriers to become “short sleepers”, meaning they need less sleep! Two women, a mother and daughter, who have this mutation require only 6 hours of sleep without a negative impact. Apparently they can do this because they have a more efficient sleep, with more intense REM states, which was observed in mice with the same mutations.

Why is this important, you may ask? Someday this will help scientists in the treatment of certain debilitating sleep disorders. On a more selfish note, it might even help scientists to develop a biological treatment that allows us regular folk to function just as well as we already do, with less sleep. Just think of the things you could accomplish with a few extra hours!