31 October 2011

Programmed to be Zombies? Stealth Genetics of Brain Transformation

Once thought to be rare, these events actually take place surprisingly often. According to one recent estimate, they occur in many or most brain cells, perhaps several hundred times within each cell...Many of the insertion sites were located within genes that play key roles in normal brain function. These include genes encoding receptors for the neurotransmitter dopamine and membrane transporters that mop up neurotransmitter molecules from the spaces between neurons after their signaling is complete... Others were found in genes encoding regulatory proteins that are linked to psychiatric illnesses such as schizophrenia and the developmental disorder Smith–Magenis syndrome. _SciAm
Slow Progressive Stealth Zombie Transformation

What if the people around us are not who we think they are? What if we continue to see them as someone they once resembled, while they have been subtly changing over time to something else?

Humans are defined by their brains. We know that their brains are shaped by a host of chance events involving genes, experiences, accidents etc. But what if these brains are changing in ways we do not understand, in ways we cannot control, so that over time these persons around us have changed into something else? I am not talking about diseases of the brain, but something much more subtle.

Here is a glimpse into the genetics of stealthy brain transformation which may help explain why that person next to you is not who you think they are:
Mobile DNA molecules that jump from one location in the genome to another may contribute to neurological diseases and could have subtle influences on normal brain function and behavior, according to a study published October 30 in Nature. (Scientific American is part of Nature Publishing Group.)

Retrotransposons are mobile genetic elements that use a copy-and-paste mechanism to insert extra copies of themselves throughout the genome. First discovered in plants about 60 years ago, they are now known to make up more than 40 percent of the entire human genome and may play an important role in genome evolution.

...The researchers also found that there was far more jumping-gene activity in the hippocampus than in the caudate nucleus. This is interesting, because the hippocampus is known to be critical for learning and memory, and is widely thought to be one of the few parts of the brain that continues to produce new cells throughout life. "It is tempting to speculate that genetic differences between individual neurons could impact memory," Faulkner says, "but we have no evidence yet that this is the case."

Retrotransposons are normally silenced to prevent harmful mutations from occurring in egg and sperm cells, but are mobilized during certain stages of brain development, when neurons are being produced from dividing stem cells. Retrotransposons then take the opportunity to jump at random into parts of the chromosome that have been opened up for DNA replication.

As well as generating mutations by inserting themselves into and disrupting genes, retrotransposons can alter gene activity if inserted into adjacent regulatory regions of DNA.

...Once thought to be rare, these events actually take place surprisingly often. According to one recent estimate, they occur in many or most brain cells, perhaps several hundred times within each cell
. Each neuron is likely subjected to a unique combination of insertions, leading to a genetic variability within populations of cells.

The full significance of this "genomic plasticity" is still not clear, but the authors suggest that it could influence brain development and behavior. It may, for example, partly account for the differences in brain structure and behavior between identical twins, and could even affect thought processes by subtly influencing the changes in nerve cell connections that occur with experience. _SciAm

It is becoming more and more difficult to claim that all humans are essentially the same, genetically. In fact, it is becoming more difficult to say that a person is the same today, genetically, as he was yesterday. Conventional methods of genomic sequencing do not detect many of these subtle genetic and epigenetic differences, suggesting the need for more sophisticated tools and screening methods.

One thing is certain: This changing nature of the brain -- the core of a human's self and being -- will require some rethinking of how societies should be organised. Humans with changing brains will need to be raised and taught to live in a dynamic and changing society. They must be given tools of competence, self reliance, and resilience. And they must be given the freedom to adapt to the inevitable changes which always occur.

Just the opposite of the traits one sees in the sheltered, academically lobotomised psychological neotenate -- who demands to be taken care of his entire life.

We can no longer afford this longing for dependency and stasis which defines most modern welfare state mentalities. This headlong rush for security, this raucous cry to be taken care of by an all-powerful state -- we cannot afford this delusional belief any longer. In a world of clashing cultures, this whining chorus of wankers is a suicidal lullaby. Particularly when the core populations of these affluent societies is shrinking so quickly.

Humans must learn to expect massive, dynamic changes over the course of their lives, both outside themselves and inside themselves. They must learn to be prepared to meet these changes on their own terms.

Retrotransposons and Human Genome Evolution

Abstract of Nature study:
Retrotransposons are mobile genetic elements that use a germline ‘copy-and-paste’ mechanism to spread throughout metazoan genomes1. At least 50 per cent of the human genome is derived from retrotransposons, with three active families (L1, Alu and SVA) associated with insertional mutagenesis and disease2, 3. Epigenetic and post-transcriptional suppression block retrotransposition in somatic cells4, 5, excluding early embryo development and some malignancies6, 7. Recent reports of L1 expression8, 9 and copy number variation10, 11 in the human brain suggest that L1 mobilization may also occur during later development. However, the corresponding integration sites have not been mapped. Here we apply a high-throughput method to identify numerous L1, Alu and SVA germline mutations, as well as 7,743 putative somatic L1 insertions, in the hippocampus and caudate nucleus of three individuals. Surprisingly, we also found 13,692 somatic Alu insertions and 1,350 SVA insertions. Our results demonstrate that retrotransposons mobilize to protein-coding genes differentially expressed and active in the brain. Thus, somatic genome mosaicism driven by retrotransposition may reshape the genetic circuitry that underpins normal and abnormal neurobiological processes.
More: Scientists key on changes in brain gene expression over the lifetime
In the studies, published in the Oct. 27 Nature, researchers focused not on DNA — virtually every cell’s raw genetic material is identical — but on when, where and for how long each gene is turned on over the course of a person’s life. To do this, the researchers measured levels of mRNA, a molecule whose appearance marks one of the first steps in executing the orders contained in a gene, in postmortem samples of donated brains that ranged in age from weeks after conception to old age.

...To see what those genes were up to, Šestan’s study examined mRNA levels of different genes in 57 brain samples. The team divided the brain tissue up by region, so they were also able to get an idea of genes’ behavior in different parts of the brain. A parallel study, headed by Joel Kleinman of the National Institute of Mental Health in Bethesda, looked at gene behavior in 269 brain samples from a single region called the prefrontal cortex that also spanned the lifetime.

This approach allowed the researchers to get access to the brain that had previously been impossible. _Sciencenews

We also need to remember that drug use triggers changes in brain gene expression -- some of these changes can be long-term or even "permanent." This is particularly tragic in the case of fetal brain exposure to drugs such as alcohol, methamphetamine, crack cocaine, etc. in the womb. But adolescents and young adults are also quite vulnerable to changes in brain gene expression from drug use. Bonus question: What are the most effective cultures and incubators for drug use in societies? Schools, and anywhere young peers are concentrated and on their own.

Long term behavioural change following ingestion of magic mushrooms More

Brain changes from cannabis use

And there are always new party drugs coming down the pipeline which will have unknown short and long-term effects on the brain, and brain gene expression.

Some people are naturally programmed to be zombies. Other people have to work at it.

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