Researchers map 'switches' that shaped the evolution of the human brain

March 5, 2015
The human version of a DNA sequence was inserted into a mouse embryo, and could be turned on a gene in the cortex during brain development. (Gene activity is stained blue.) Credit: Steven K. Reilly

Thousands of genetic "dimmer" switches, regions of DNA known as regulatory elements, were turned up high during human evolution in the developing cerebral cortex, according to new research from the Yale School of Medicine.

Unlike in and mice, these switches show increased activity in humans, where they may drive the expression of genes in the , the region of the brain that is involved in conscious thought and language. This difference may explain why the structure and function of that part of the brain is so unique in humans compared to other mammals.

The research, led by James P. Noonan, Steven K. Reilly, and Jun Yin, is published March 6 in the journal Science.

In addition to creating a rich and detailed catalogue of -specific changes in gene regulation, Noonan and his colleagues pinpointed several potentially guided by these regulatory elements that are crucial to human brain development.

"Building a more complex cortex likely involves several things: making more cells, modifying the functions of cortical areas, and changing the connections neurons make with each other. And the regulatory changes we found in humans are associated with those processes," said Noonan, associate professor of genetics, an investigator with the Kavli Institute for Neuroscience, and senior author of the study. "This likely involves evolutionary modifications to cellular proliferation, cortical patterning, and other developmental processes that are generally well conserved across many species."

Scientists have become adept at comparing the genomes of different species to identify the DNA sequence changes that underlie those differences. But many human genes are very similar to those of other primates, which suggests that changes in the way genes are regulated—in addition to changes in the genes themselves—is what sets human biology apart.

Up to this point, however, it has been very challenging to measure those changes and figure out their impact, especially in the developing brain. The Yale researchers took advantage of new experimental and computational tools to identify active regulatory elements—those DNA sequences that switch genes on or off at specific times and in specific cell types—directly in the human cortex and to study their biological effects.

First, Noonan and his colleagues mapped active regulatory elements in the human genome during the first 12 weeks of cortical development by searching for specific biochemical, or "epigenetic" modifications. They did the same in the developing brains of rhesus monkeys and mice, then compared the three maps to identify those elements that showed greater activity in the developing human brain. They found several thousand regulatory elements that showed increased activity in human.

Next, they wanted to know the biological impact of those regulatory changes. The team turned to BrainSpan, a freely available digital atlas of gene expression in the brain throughout the human lifespan. (BrainSpan was led by Kavli Institute member Nenad Sestan at Yale, with contributions from Noonan and Pasko Rakic, a co-author on this study.) They used those data to identify groups of genes that showed coordinated expression in the cerebral cortex. They then overlaid the regulatory changes they had found with these groups of genes and identified several biological processes associated with a surprisingly high number of regulatory changes in humans.

"While we often think of the as a highly innovative structure, it's been surprising that so many of these seem to play a role in ancient processes important for building the cortex in all mammals, said first author Steven Reilly. "However, this is often a hallmark of evolution, tinkering with the tools available to produce new features and functions."

Next, Noonan and colleagues plan to investigate the function of some of the regulatory changes they identified by introducing them into the mouse genome and studying their effects on mouse brain development.

Explore further: A gene for brain size only found in humans

More information: Evolutionary changes in promoter and enhancer activity during human corticogenesis, Science, www.sciencemag.org/lookup/doi/10.1126/science.1260943

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JVK
1 / 5 (3) Mar 05, 2015
"While we often think of the human brain as a highly innovative structure, it's been surprising that so many of these regulatory elements seem to play a role in ancient processes important for building the cortex in all mammals, said first author Steven Reilly. "However, this is often a hallmark of evolution, tinkering with the tools available to produce new features and functions."

See also: Scientists discover new roles for viral genes in the human genome http://phys.org/n...man.html

Both groups are explaining how ecological variation leads to ecological adaptations via nutrient-dependent microRNAs, The nutrient-dependent microRNAs are required for the balance of viral microRNAs and nutrient dependent microRNAS to link nutrient-dependent RNA-mediated amino acid substitutions from entropic elasticity to anti-entropic effects on DNA stability during life history transitions of invertebrates and vertebrates with brains.
Vietvet
3 / 5 (4) Mar 05, 2015


Both groups are explaining how ecological variation leads to ecological adaptations via nutrient-dependent microRNAs, The nutrient-dependent microRNAs are required for the balance of viral microRNAs and nutrient dependent microRNAS to link nutrient-dependent RNA-mediated amino acid substitutions from entropic elasticity to anti-entropic effects on DNA stability during life history transitions of invertebrates and vertebrates with brains.


There you go again JVK, falsely claiming studies support your creationist pseudo science.
JVK
1 / 5 (3) Mar 05, 2015
MicroRNA-Driven Developmental Remodeling in the Brain Distinguishes Humans from Other Primates http://dx.doi.org....1001214

Reported in December 2011 as http://www.the-sc...istance/
"The big finding that it is a trans element is in some ways a lot more interesting to me than the specific [microRNAs] that they pulled," said Eric Vallender, an evolutionary neurogeneticist at Harvard Medical School who was not involved in the research. The dominance of trans rather than cis regulatory changes is surprising, he said, and "has some fairly important implications for how we pursue these types of questions in the future."

http://www.ncbi.n...24693353 Nutrient-dependent/pheromone-controlled adaptive evolution: a model.

See also: https://www.faceb...ediated/
JVK
1 / 5 (3) Mar 05, 2015
Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq
http://www.scienc...abstract

"...the complex microanatomy of the brain can be revealed by the RNAs expressed in its cells."

Search Results for: RNA-mediated
http://perfumingt...mit.y=13
Number of Results: 220

https://www.googl...mediated
JVK
1 / 5 (3) Mar 06, 2015
Jay R. Feierman banned me from participation on the ISHE's human ethology group despite my award- winning publication with other ethologists.

See: Human pheromones: integrating neuroendocrinology and ethology http://www.nel.ed...view.htm

He banned me when I refused to answer YES or NO to a question about RNA-mediated amino acid substitutions, which link ecological variation to ecological adaptation in species from microbes to man via conserved molecular mechanisms that we detailed in a 1996 review "From Fertilization to Adult Sexual Behavior" http://www.hawaii...ion.html

Feierman never grasped any aspect of molecular epigenetics, which links RNA-mediated events across species. On several occasions, he asked "What about birds?"

He also just posted this link: http://rstb.royal...287?etoc

There are no questions about RNA-mediated events in any species.
JVK
1 / 5 (3) Mar 06, 2015
Biology, molecular and organismic (1964) http://icb.oxford...citation

"The notion has gained some currency that the only worthwhile biology is molecular biology. All else is "bird watching" or "butterfly collecting." Bird watching and butterfly collecting are occupations manifestly unworthy of serious scientists!" p. 443

Nothing in Biology Makes Any Sense Except in the Light of Evolution (1973) http://www.jstor..../4444260

"...the so-called alpha chains of hemoglobin have identical sequences of amino acids in man and the chimpanzee, but they differ in a single amino acid (out of 141) in the gorilla." p. 127

(2015) Every inch a finch: a commentary on Grant (1993) 'Hybridization of Darwin's finches on Isla Daphne Major, Galapagos' http://rstb.royal...287?etoc

"The 1993 paper makes it clear that Darwin's finches are an instance of ecological speciation in the presence of hybridization."
anonymous_9001
5 / 5 (3) Mar 06, 2015
"The notion has gained some currency that the only worthwhile biology is molecular biology. All else is "bird watching" or "butterfly collecting." Bird watching and butterfly collecting are occupations manifestly unworthy of serious scientists!" p. 443


You seem to have forgotten the important part again. Don't worry, I got it-

Such pronunciamentos can be dismissed as merely ridiculous.


If you're going to freak out about context every time I post correspondences from scientists I've contacted, it's only fair I give you the same treatment about Dobzhansky, hypocrite.
JVK
1 / 5 (3) Mar 06, 2015
Is Most of Our DNA Garbage?
http://www.nytime...tml?_r=0

Zimmer hedges his bets but, as always, comes out on the side of the biologically uninformed researchers who have not yet learned the difference between amino acid substitutions and mutations.

Ecological variation is the raw material by which natural selection can drive evolutionary divergence [1–4].
http://rspb.royal...81.short

RNA-directed DNA methylation and RNA-mediated amino acid substitutions link ecological variation to ecological adaptations manifested in biodiversity.

...mutations provide the "raw material" upon which the mechanisms of natural selection can act.
http://publicatio...er1.html

No, they don't. Only the biologically uninformed believe in that pseudoscientific nonsense. Find out who some of them are when you read the latest from Carl Zimmer.
JVK
1 / 5 (3) Mar 06, 2015
...it's only fair I give you the same treatment about Dobzhansky, hypocrite.


I've provided a link to the full text of the article several times. It's free.
http://icb.oxford...citation

He also mentioned that "Ingram and others found that hemoglobin S differs from A in the substitution of just a single amino acid, valine in place of glutamic acid in the beta chain of the hemoglobin molecule."

That was the first indication the S variant is an ecological adaptation, a fact that has become obvious during the past 50 years. It is a good reason to read the entirety of his 1964 review to see how much ignorance remains among those he referred to correctly as "bird-watchers" and "butterfly collectors." To my knowledge, none of them have ever become serious scientists.

But you know, Jay R. Feierman, who is an even better example of that fact than you will ever be. He has remained a biologically uniformed science idiot for many decades.
anonymous_9001
5 / 5 (3) Mar 06, 2015
He also mentioned that "Ingram and others found that hemoglobin S differs from A in the substitution of just a single amino acid, valine in place of glutamic acid in the beta chain of the hemoglobin molecule."


And do you know the source of that substitution? I'll give you a hint: it doesn't take place post-transcriptionally.
JVK
1 / 5 (3) Mar 06, 2015
Amino acid substitutions are nutrient-dependent and they are fixed in the DNA of organized genomes via the physiology of reproduction. The S variant is most closely associated with ingestion of fermented milk products and grains.

Jay Feierman banned me when I refused to address your sophomoric pseudoscientific nonsense. If you think you know anything about the source of the hemoglobin S variant, tell us all. Stop playing your ridiculous games and wasting everyone's time.

6/14/14/
[MODERATOR NOTE: I'm not going to post more from Kohl until he answers the very direct and simple question posed to him by anon, which is whether he (Kohl) believes that RNA splicing can change DNA.]IE

anon is the anonymous fool known here as "anonymous_9001" and elsewhere as Andrew Jones a worker at McDonald's who nevertheless earned a degree in biology via work that included a thesis on his mutagenesis experiments. He is a science idiot who is well-respected by other science idiots.
anonymous_9001
5 / 5 (3) Mar 06, 2015
Amino acid substitutions are nutrient-dependent and they are fixed in the DNA of organized genomes via the physiology of reproduction. The S variant is most closely associated with ingestion of fermented milk products and grains.


Do you know how many people globally ingest fermented milk products and grains? Far more than those with the S variant. If eating those CAUSED the DNA change, the vast majority of us would have sickle cell.

In the same way, if citrate CAUSED the promoter shift in Lenski's experiment, 12/12 of his populations should have acquired the cit+ trait instead of just 2/12.
JVK
1 / 5 (3) Mar 06, 2015
Do you know how many moth larvae globally ingest lead and manganese contaminated leaves that cause them to become pepper-colored adults via the physiology of their nutrient-dependent pheromone-controlled reproduction? Let's compare them to the fawn-colored moths that have survived bird predation and the extant human populations that have survived snake predation.

The peppered moth and industrial melanism: evolution of a natural selection case study
http://dx.doi.org....2012.92

Testing the snake-detection hypothesis: Larger early posterior negativity in humans to pictures of snakes than to pictures of other reptiles, spiders and slugs http://www.fronti...14.00691

Alternatively, just make up more pseudoscientific nonsense than any serious scientist can stand, until you are declared a hopelessly biologically uninformed science idiot.
anonymous_9001
5 / 5 (3) Mar 06, 2015
Do you know how many moth larvae globally ingest lead and manganese contaminated leaves that cause them to become pepper-colored adults via the physiology of their nutrient-dependent pheromone-controlled reproduction?


As I've pointed out before, the hypothesis that stated their diet caused the color change has been debunked by multiple follow-up studies.

Also, in order to claim that the dark moths thrived due to stronger sexual selection due to a more attractive pheromone blend, you would have to perform an experiment where you isolated that as the sole variable without predation to effect the results. Has this been done? Was it demonstrated that the dark moths had a different pheromone blend than the light moths in the first place?

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