15 February 2012

You're So Special!

In the past few years the two of us and our colleagues have come on especially intriguing suspects that seem to operate more in the brain than in other tissues: jumping genes. Such genes, which have been found in virtually all species, including humans, can paste copies of themselves into other parts of the genome (the full set of DNA in the nucleus) and alter the functioning of the affected cell, making it behave differently from an otherwise identical cell right next to it. Many such insertions in many different cells would be expected to yield subtle or not so subtle differences in cognitive abilities, personality traits and susceptibility to neurological problems. _SciAm

This animation by Muotri and Marchetto shows the higher rate of activity of the jumping genes in the Rett-afflicted cells (more green dots) than in the WT (wild type) ones. (The olfactory bulb is shown in red, the striatum in magenta and the cerebellum in cyan.) _SciAm

Jumping gene transposons are capable of inserting significant differences in the gene expression of identical twins. When these differences are inserted into brain cell DNA, they can cause identical twins to behave and perform differently from one another. Scientists have barely begun to understand how important this mechanism is to both long term evolution and rapid short term variation.

Nature to scientists: "Everything you think you know, just ain't so!"
Retrotransposons make up as much as half of the nucleotides, or DNA building blocks, in the human genome. In contrast, the approximately 25,000 protein-coding genes we possess make up less than 2 percent of mammalian DNA. The jumping genes are descendants of the first primitive molecular replication systems that invaded the genomes of eukaryotes (organisms having cells that contain a nucleus) long ago. A group led by Haig H. Kazazian, Jr., at the University of Pennsylvania showed in 1988 that retrotransposons, which were once thought of as nonfunctional junk DNA, were active in human tissues.

...Retrotransposition often fails to run its course, which produces truncated, nonfunctional copies of the original L1 DNA. Sometimes these snippets (or the whole L1 copy) have no effect on a protein-coding gene. Other times, though, they can have any of several consequences, both good and bad, for a cell’s fate. They may, for instance, drop into and thus alter the protein-coding region of a gene. This maneuver can lead to creation of a new variant of the protein that helps or harms an organism. Or this positioning may stop a given protein from being made. In other instances, the newly pasted DNA may fall outside of a coding region but act as a promoter (a switch that can turn on nearby genes) and alter the level of gene expression—the amount of protein made from the gene—with, once again, good or bad results for the cell and the organism. When LI retrotransposons end up in many places in neurons or in many cells of the brain, or both, the brain will be very different from the one that would have formed without their influence. It stands to reason that such genetic mosaicism could affect behavior, cognition and disease risk and could also help explain why one identical twin may remain disease-free when a sibling is diagnosed with schizophrenia, for example.

...The continuing research into jumping genes in the brain could potentially challenge an entire academic discipline. Behavioral geneticists often follow groups of identical twins over long periods to control for the effects of genes and determine the environmental contributions to such disorders as schizophrenia. The new findings showing that jumping genes actively revise genomes after an embryo forms question the assumption that “identical” twins are genetically alike. Indeed, the new discoveries will make it ever harder to disentangle the relative effects of nature and nurture on our psyches.

The question remains: Why has evolution not destroyed these vestiges of ancient viruses from within our cells, given that jumping genes have a high chance of introducing potentially fatal genetic flaws? To answer the question, we should acknowledge that humans have always been under attack by viral parasites and other invaders that expand the size of our genomes with jumping DNA. The bodies of humans and our evolutionary forebears may not have been able to fully eliminate the interlopers, but they have adapted to at least coexist with the invaders by silencing them through a variety of clever mechanisms that mutate and disable them. It also appears that, in some cases, our genomes have commandeered the genetic machinery of L1 retroelements to enhance our own survival, which is one reason that cells may sometimes allow, or even encourage, L1s to jump around the genome under carefully controlled conditions. _SciAm
Evolution has always been something of a crap shoot. The wider the range of variation that can be generated, the more likely to find suitable fits for various environmental niches.

What does this mean for the genetics of behaviour and intelligence differences? It means quite the opposite of what the authors above suggest. In the past, behavioural differences in identical twins have been attributed largely to differences in non-shared environment. Now we know better. Rather than detracting from the importance of the genes in influencing behaviours and aptitudes, this research intensifies the importance of genes and gene regulation.

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Blogger Bruce Hall said...

"this research intensifies the importance of genes and gene regulation."

Be careful how you phrase things. Some government official will see that as justification for the new Office of Genetic Regulation.

Wednesday, 15 February, 2012  
Blogger al fin said...

It may be too late to prevent that from occurring.

Government gets more of what it subsidises and less of what it taxes and punishes.

When government punishes competence and production and subsidises failure, in some ways it is already regulating particular kinds of genes.

Wednesday, 15 February, 2012  

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“During times of universal deceit, telling the truth becomes a revolutionary act” _George Orwell

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