Wednesday, 21 March 2012

Finding the source of Individuality

Have you ever wondered at the uniqueness of every individual around you? Including yourself. Even identical twins that have the same set of genes and have grown up together differ in some of their characteristics and personality. This brings up the old question of nature/ nurture. Recent research findings show that the answer may lie in certain type of DNA within a class called Mobile Genetic Elements (MGE). More specifically, the ones found moving in the brain are called Retratransposons.

Retratransposons like the Long Interspersed Element (L1) for example, follow a copy and paste method to move itself around. It is able to do this because it is thought that L1 retratransposons encode for all the ‘machinery’ it requires to move itself.  The original L1 segment of DNA first transcribes itself into its RNA form following which, the RNA strand moves out of the nucleus to synthesize the proteins in its code. This RNA strand and protein complex then re-enter the nucleus where one of the proteins, endonuclease creates nicks in the existing DNA. At this point, the RNA is retranscribed by the endonuclease into a double stranded DNA which is then inserted into the nicked area.

Transposon events cause the mosaicism
 seen in the color of corn kernels.

This was seen as fascinating because such an explicit change of the DNA within humans is not seen in any other cell excepting immune cells where it is necessary to help churn out new antibodies to fight new diseases.  Although mobile elements were discovered in the 1940’s by Barbara McClintock which resulted in the famous ‘multi-coloured’ corn, its presence and activity in human cells has been a recent discovery. Working with mice and post-mortem samples of the human brain, Professor Fred H. Gage and colleagues discovered that these mobile elements are ‘switched off’ in most human somatic cells except in the hippocampus in the brain from where new neurons are ‘born’. It was found that these mobile elements are extraordinarily active within the neural progenitor cells in the hippocampus with an average of 80-100 L1 jumps per cell. This find is particularly interesting due to the consequences of each jump.

During the early stages of human nervous system development LINE-1 elements become active (indicated by green flourescence) possibly affecting neuronal function. 

When a L1 DNA segment inserts itself into a new area in the genome, it can have several different effects depending on insertion site. On occasion, the new DNA may not have any effect whatsoever. However, the other effects can either be good or bad. If the L1 insertion site is within a DNA segment coding for a protein, the insertion may disrupt the code thus preventing any protein being made or may produce a new variant of the protein. On the other hand, the L1 DNA can act as a promoter if it inserts itself just outside a coding segment in the DNA. This means that it can either ‘turn off’ or ‘turn on’ that segment resulting in the inhibition or production of a certain protein. On a wide scale, this leads to a huge amount of diversity between cells in the brain. As Gage says, “This is a potential mechanism to create the neural diversity that makes each person unique." Thus, this also makes humans “true chimeras”.

Retratransposons have garnered increased interest due to research showing that L1 insertions play a part in neurological and psychiatric conditions. Although further research is required to be carried out, this is a field that holds many promises and discoveries especially since up to 50% of the human DNA is made up of Mobile Elements.

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