“Jumping Genes”: Our Genetic Sequences Aren't Set in Stone

Our genetic material is complex—so complex that 
even now we’re still discovering new things about it.

When we learned about DNA and genetics in class, we learned that our genomes contain alleles which code for genotypes that determine our phenotypes (our traits). DNA replication is a very delicate process and, although it occurs at rapid rates, there are very few mistakes. Enzymes exist which would correct any mistakes made, as even a simple base substitution mutation—that is, the changing of one nucleotide for another (for example, the change of adenine to thymine, guanine, or cytosine) could result in a disorder that can plague a person their whole life. An example of this is sickle cell anemia. In individuals with sickle cell anemia, the base adenine in the codon GAG which codes for glutamic acid in hemoglobin is exchanged for thymine, so that the codon becomes GTG and codes for valine instead. Hemoglobin is the protein found in red blood cells which is responsible for binding oxygen. Due to the change in amino acid, hemoglobin’s structure is distorted and so is the shape of the red blood cell—changing from the flattened disk shape to a curved, sickle-like shape.  This leads to weakness, fatigue, and shortness of breath because the abnormal hemoglobin doesn’t carry oxygen as efficiently as normal hemoglobin does, and can crystallize in blood vessels. Given that even the change of one base in our DNA can have profound consequences, we would assume that our genomes are, in general, quite fixed throughout our lives, unless we develop a disorder. Recent studies show that that is not the case.

Within our genome, there are DNA molecules that can jump from one locus to another, and might influence brain function and behavior. “Retrotransposons” are one such type of mobile DNA which copy-paste themselves into various areas of the genome, and have been found to compose over 40% of the human genome. In order to investigate this phenomenon, the Roslin Institute in Edinburgh, Scotland, undertook the task of mapping the retrotransposon insertion sites in human brain cells. These brain cells were extracted from the tissue of healthy individuals who showed no sign of disease or abnormality after they passed away.

What they found was that, even when looking at only the hippocampus (which is responsible for memory) and the caudate nucleus, there was a dizzyingly large number of retrotransposon insertion sites—specifically, 25,000 different sites! These genes were found to integrate themselves in “genes that were expressed in the brain.”  This is due to the fact that, normally, our chromosomes are coiled in such a way that they aren’t always accessible for transcription and, in this case, retrotransposon insertion. Examples of such genes include neurotransmitter receptors in neurons, membrane transporters that remove remaining neurotransmitters from the synaptic gap after the signal has been transmitted to the post-synaptic neuron, genes which suppress tumor growth (which are deleted in brain cancer patients) and those which have been linked to psychiatric disorders such as schizophrenia.

As would be expected, retrotransposon activity is normally suppressed in order to prevent mutation that could negatively affect developing gametes, but during brain development, when stem cells are dividing to produce new neurons, they are mobilized and insert themselves into accessible areas of the chromosome during DNA replication when the two strands of the double helix are separated. Since the hippocampus is responsible for learning and memory, and therefore produces new cells throughout the human life span, retrotransposon activity in this area of the brain was found to be higher than in the caudate nucleus.

 Diagram showing retrotransposition

These jumping genes insert themselves into random areas in the genome quite often, occurring several hundred times in most brain cells, and resulting in genetic variability within these cells. When inserted, they can cause mutations which express themselves negatively, but it is also possible that retrotransposon activity could influence our behavior and neural activity in ways that aren’t always bad. As Faulkner says, “it is entirely possible that retrotransposition is generally a good thing but sometimes contributes to disease.”

I find these jumping genes quite interesting and believe that we could better understand brain disorder and behavioral changes from analyzing how and under what conditions will retrotransposition cause harm to brain cells.  It is well understood that human cells are able to replicate masses of DNA within short periods of time with a mechanism to prevent or minimize errors. Understanding how and under what conditions adverse mutation can occur might allow us to help our body deal with retrotransposition so that, when such DNA sequences are copy-pasted into random regions of the genome, they don’t cause harm, and simply give genetic variability in our cell populations.

Genetic variety helps living organisms survive through sometimes drastically changing conditions and environments. Plants cross pollinate in order to create genetic diversity so that disasters like epidemics don’t wipe out the whole species. Humans achieve genetic variety through crossing over and random orientation of homologous chromosomes during meiosis I. Perhaps retrotransposition is another means by which humans have been attempting to achieve genetic variety, so that in survival of the fittest, we are able to deal with harmful external factors and better our chances of not going extinct.

Images:

http://upload.wikimedia.org/wikipedia/commons/thumb/5/50/L1_Retrotransposon.jpg/400px-L1_Retrotransposon.jpg

http://sahavicha.kalasin3.go.th/UserFiles/Image/DNA.jpg