20 February 2015

Mouse brain grew thanks to human gene

Scientists: Human "junk DNA" transplant enlarged mouse brain

RIA NewsGeneticists and neurophysiologists have discovered a unique fragment of "junk DNA" (in fact, as it is clear from what is written below, it is absolutely not junk, but a fully functional enhancer gene - VM), accelerating and stimulating the growth of cells in the brain of a human embryo, whose transplantation into the mouse genome led to an increase in the mass of its brain by 12% compared with a similar site extracted from chimpanzee DNA, according to an article published in the journal Current Biology (Boyd et al., Human-Chimpanzee Differences in a FZD8 Enhancer Alter Cell-Cycle Dynamics in the Developing Neocortex – VM).


Diagram from an article in Current Biology – VM

"What we have found is only a small part of the genetic background of why our brains are noticeably larger than those of all other primates. Our research has very clearly shown how complex the changes that our ancestors experienced during evolution were. Most likely, the phenomenon we discovered is only a small part of this genetic puzzle," said Gregory Wray from Duke University in Durham (USA).

As Ray and his colleagues note, the genomes of humans and chimpanzees coincide by 99%, but our nervous systems develop completely differently and suffer from different problems in old age. These differences prevent scientists from using primates to study various diseases and how humans acquired the ability to speak and think intelligibly.

In recent years, scientists have discovered several hundred genes responsible for brain development and differing in structure in the genomes of humans and chimpanzees. However, they were never able to find those sections of DNA that were responsible for the unusually large, compared to the rest of the body, the size of our brain. Therefore, neurophysiologists and geneticists have long suspected that the reason for the striking difference between the two species lies not so much in the structure of genes as in their different activity.

Ray's group showed that the size and properties of the human brain are the product not only of unique features in the structure and "readability" of genes, but also in how the "junk DNA" is arranged, which is not responsible for the formation of proteins.

Comparing the parts of the genome that are especially active in the brain of a chimpanzee embryo and a human, the authors of the article identified about a hundred fragments of "junk DNA", the structure of which has changed especially over the seven million years of evolution separating us from monkeys. Scientists methodically inserted these pieces of genetic code into the DNA of laboratory mice, and then monitored the development of embryos, trying to fix any noticeable changes.

As this painstaking and extremely long experiment showed, only six "garbage" sites showed activity after transplantation and caused some changes in brain development. One of them, named HARE5, so strongly influenced the development of the mouse brain that the changes were visible to the naked eye.


A snapshot of a mouse embryo with an enlarged cerebral cortex
from the Duke University Press Release: Evolving a Bigger Brain With Human DNA – VM

It belongs to the category of so–called "enhancers" - short sequences of several thousand or hundreds of genetic "letters"-nucleotides that connect with proteins and other components of the gene reading system and force them to actively read a particular gene. In our case, HARE5 enhances the work of the FRZ8 gene, which is located next to it on the DNA molecule and is responsible for the growth of cells of the future brain.

According to scientists, the human and monkey versions of HARE5 differ by only 16 "letters", but this is enough for the brain of mouse embryos to begin to develop completely differently. Human HARE5 accelerates the growth of nerve cells and causes them to divide faster than the same section of chimpanzee DNA, as a result of which the brain of the future mouse becomes 12% larger.

While scientists do not know whether rodents will acquire "superintelligence" as a result of such genome modification – all embryos were destroyed after experiments. In the near future, Ray and his colleagues plan to grow a similar mouse, and check whether it will become a "Brain" from the famous Steven Spielberg animated series about intelligent laboratory mice obsessed with the idea of taking over the world.

Portal "Eternal youth" http://vechnayamolodost.ru20.02.2015

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