your brain's genes keep changing - jumping genes at work

 Jumped gene generated protein in brain

One of the most fascinating recent developments in brain genetics, IMHO, is the discovery that there are "jumping genes" that function well after you leave the womb, in fact even now in your life, to generate new learning abilities, determine how you react to fear and respond to stress and even whether or not you will have a severe neurological disorder.

Work published by Coufal, Nicole, et. al at the Salk Institute, the University of Michigan, etc. in Nature, Vol. 460, Aug. 27, 2009 entitled L1 Retrotransposition in Human Neural  Progenitor Cells, from which this picture is taken, have demonstrated that there are "jumping genes", particularly in the brain, that are capable of "copying and pasting" copies of themselves into other parts of the DNA of the brain to make a given cell behave differently from an adjacent cell.

It is standard procedure in psychological studies to follow identical twins raised by the same parents to see what differences, which are often very significant, emerge as they develop.  Differences in behavior, incidence of neurodegenerative disease or mental illness, as well as mental functioning, were attributed to "environment"/"nurture", which varied over life, rather than "nature" which was assumed to be fixed at birth with no changes in neural structure over our life.

Coufal, et. al., however, showed that mice that were bred to be genetically identical, and were handled in exactly the same way in the same laboratory environment displayed great differences in their behavior, learning ability and reactions to fear and stress.  They surmised that there was something other than "nurture"/"environment" to explain theses radical differences, but how could the "nature" of the brains of these mice change after they were born?

Jumping genes in corn change pigmentation

The idea that there was something like mobile elements in the genome originated with Barbara McClintock's 1983 Nobel Prize winning work on corn.   She was credited with developing the term "transposons" and "jumping genes" in her seminal paper of 1948.  The unstable phenotypes in the pigment gene were acted upon by these jumping genes to cause different variations even in adjacent kernels.

These "copy and paste" retrotransposons were not demonstrated to exist in humans until 1988 at the University of Pennsylvania by Hazazian, Jr, Hair, and Moran, John in The Impact of L1 retrotranspons on the human genome, in Nature Genetics, 19, 19-24, 1999. et. al.  

When the "copy and paste" operation takes place, often there is no effect on the gene's protein production/coding operation, but they can have good, or bad, consequences.  If a new variant of an existing protein is produced, it can have either good, or bad results for the cell and for the entire organism.  The "successful" retrotransposons can/will produce a changed brain, often very different.  It is believed to affect why one identical twin may have schizophrenia, or autism, while the other remains healthy.  

Hippocampus

It had been assumed that jumping genes only occurred in the cells of the ovaries and testes.  They have now been found in nonsex cells in early development and later in life as well, being more  active in the brain than elsewhere, a direct contradiction to the belief that the genetic codes in human brain cells remain stable throughout life.  The fluorescing protein in the figure above was generated in a mouse brain cell that gives rise to hippocampal neurons.  This was a key finding.

There are only two places in the brain where new neurons are generated,  a process called neurogenesis, which is necessary for retrotransposition to occur; the hippocampus and the caudate nucleus.  Both of these areas are involved in memory.   It was also found in mice that exercise and exposure to new and unusual situations might spur gene jumping.  Amazingly, the number of neurogenetic events increased 2X under these conditions.

Tatjana Singer, et. al. in "Line- Retrotranspons: Mediators of Somatic Variation in Neuronal Genomes?" in Trends in Neurosciences. Vol 33, 8, Aug 2010 showed that the brains of humans and mice with Rett syndrome showed a significant increase in the number of L1 "jumping gene" insertions in a mutation in a specific gene which can induce this severe brain disorder.  L1 jumping genes have also been tied to schizophrenia with the discovery that the frontal cortex regions of affected individuals showed increased levels of retrotransposons.  Autism has also been circumstantially linked to L1 jumping genes.

The implications of this discovery are many.  The assumption that identical twins are genetically alike is likely wrong.  The belief that our neural genetics are "fixed" at birth is almost certainly incorrect.  The arguments about whether it is "nature" or "nurture" that determines our neural functioning is now even more entangled as both are almost certainly occurring simultaneously.

The detailed explanation and model of how these retrotransposons actually operate, which is beyond the scope of this blog, is explained in lay terms in the recent issue of Scientific American in "What Makes Each Brain Unique" by Gage and Muotri.