Monday, March 2, 2015

Human DNA enlarges mouse brains and xenoxed gene trace the way of the human brain.

Fig. 1. The blue stains in these developing mice embryos show that the human DNA inserted into the rodents turns on sooner and is more widespread (right) than the chimp version of the same DNA, promoting a bigger brain.

The researches show the size of the brain of a mice has increased at inserting a piece of human DNA that controls the gene activity; "The DNA could be an important component in how the human brain was expanded" said Mary Ann Raghanti, a biologist anthropologist at Kent State University in Ohio who did not participate in the experiment.

The biologists have wondered what makes the humans humans, and now they can start to tag the molecules of our brain that allow bipedalism, varied diet, and what makes us so sucessful. En 2008, almost two dozens of comparisons of genes on humans and apes were isolated, and they produced hundreds of pieces of DNA that could be important.  But rarely the researchers have given the next step to probe that a piece of DNA has made a difference in human evolution.

Greg Wray is interested in the segments of DNA called enhacers, which control the activities of genes nearby. He and Lomax Boyd have scanned and compared different enhacers between apes and humans and in important genes nearby  for the development of the brain. With over a hundred candidates, the team  and the neurobiologist Debra Silver proved half dozen of these genes. First they inserted an enhacer in the mice embryo to observe how the genes changed. Then they inserted HARE5, the most active enhacer in cortex brain and made minigenes from the version of the gen of either apes or humans from an enhacer attached to a "reporter" gen, which turned the enhacer blue when there was an activity from the enhacer on the genes. The mice brain turned blue sooner and reported that HARE5 controls a gen called Frizzled 8, which form part of a pathway of brain development. The studies reported that the enhacer caused a great amount of stem cells  that will be part of the cortex. The mice brain with human HARE5 increased 12% more than the mice brain with the ape enhace. Now it will be proved if this increase in the brain size has made the mice smarter.

Fig. 2. The folding on the right side of this mouse embryo’s cortex reflects the increased growth stimulated by the insertion of a duplicated human gene into that side of the brain.

With this research, another team has taken this investigation furthermore, and has discovered certain gen that not only made the mice brain increase,  but also gave it distintive folds found in the brains of apes.

The new study started when Wieland Huttner, a developmental neurobiologist at the  Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, began to examinate aborted human fetal tissue and embryonic mice. “We specifically wanted to figure out which genes are active during the development of the cortex, the part of the brain that is greatly expanded in humans and other primates compared to rodents,” said Marta Florio, graduated student of Huttner who carried out the main part of the experiment.
This was more difficult. Building the cortex requieres various types of stem cells.  The stem cells divide themselves in various "intemediates" stem cells which will divide and will form neurons that will constitute the brain tissue. To learn which genes are active, the team had to separate various types of cortical stem cells.

After months of work, they resolved how to separate them.  They added fluorescent tags attached to stem cells and whereas they isolated each type of cortical cell and after  measuring the activity in genes of each stem cell, the team discovered 56 genes in human tissue that mice tissue lacks of. One of the most active genes in division of stem cells of human tissue was  ARHGAP11B, which is also under suspect of aiding human evolution.

Years ago, a group of researchers found out that the gen ARHGAP11B arose after ancestral gen made an incomplete copy of itself. While humans have an aditional version of this gen, chimps do not. They concluded duplication occurs after humans and chimp lineages splitted off. Neither mice nor apes have the gen ARHGAP11B, but modern humans and their ancestors, the Denosivans and Neanderthals do.

The team decided to put ARHGAP11B in developmental mice. The number of stem cells on cortex doubled and their brains sometimes developed folds. These folds are not seen on mice but they are in apes.  Researches found that the gen introduced caused the stem cells  became intermediate stem cells more frequently than in animals, and that these cells duplicated more frequently before turning on a neuron. These various effects increased the size of the brain.

The result “emphasizes the likelihood that this gene is indeed important during mammalian evolution for the design of a new brain, bigger and more complex,” Borrell Franco said.
This could be an important approach in how we evolutionated and  where we come from.

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