Featured Research

from universities, journals, and other organizations

Key Brain Regulatory Gene Shows Evolution In Humans

Date:
December 12, 2005
Source:
Duke University
Summary:
Researchers have discovered the first brain regulatory gene that shows clear evidence of evolution from lower primates to humans. They said the evolution of humans might well have depended in part on hyperactivation of the gene, called prodynorphin (PDYN), that plays critical roles in regulating perception, behavior and memory.

Researchers have discovered the first brain regulatory gene that shows clear evidence of evolution from lower primates to humans. They said the evolution of humans might well have depended in part on hyperactivation of the gene, called prodynorphin (PDYN), that plays critical roles in regulating perception, behavior and memory.

Related Articles


They reported that, compared to lower primates, humans possess a distinctive variant in a regulatory segment of the prodynorphin gene, which is a precursor molecule for a range of regulatory proteins called "neuropeptides." This variant increases the amount of prodynorphin produced in the brain.

While the researchers do not understand the physiological implications of the activated PDYN gene in humans, they said their finding offers an important and intriguing piece of a puzzle of the mechanism by which humans evolved from lower primates.

They also said that the discovery of this first evolutionarily selected gene is likely only the beginning of a new pathway of exploring how the pressure of natural selection influenced evolution of other genes.

They also said their finding demonstrates how evolution can act more efficiently to alter the regulatory segments, or "promoters," that determine genes' activity, rather than on the gene segment that determines the structure of the protein it produces. Such regulatory alteration, they said, can more readily generate variability than the hit-or-miss mutations that alter protein structure and function.

Proteins constitute the molecular machinery of the cell, for example, catalyzing the multitude of chemical reactions in the cell. DNA genes constitute the blueprints for such proteins, with the regulatory segments of these genes determining how actively the genes churn out proteins.

The researchers published their findings in the December 2005 issue of the Public Library of Science. They were Gregory Wray and David Goldstein of Duke University; Matthew Rockman of Princeton University; Matthew Hahn of Indiana University; Nicole Soranzo of University College London; and Fritz Zimprich of the Medical University of Vienna in Austria. The research was sponsored by the National Science Foundation and NASA.

"We focused on the prodynorphin gene because it has been shown to play a central role in so many interesting processes in the brain," said Wray. "These include a person's sense of how well they feel about themselves, their memory and their perception of pain. And it's known that people who don't make enough of prodynorphin are vulnerable to drug addiction, schizophrenia, bipolar disorders and a form of epilepsy. So, we reasoned that humans might uniquely need to make more of this substance, perhaps because our brains are bigger, or because they function differently.

"Also importantly, the part of the gene that produces the prodynorphin protein shows no variation within humans, or even between humans and any of the great apes," said Wray, who is a professor of biology. "So, if we found any variation in this gene due to evolution, it was likely to be in its regulation. And our premise is that the easiest way to generate evolutionary change is to alter regulation."

In their studies, the researchers analyzed the sequence structure of the PDYN promoter segment in humans and in seven species of non-human primates -- chimpanzees, bonobos, gorillas, orangutans, baboons, pig-tailed macaques and rhesus monkeys. They found significant mutational changes in the regulatory sequence leading to humans that indicated preservation due to positive evolutionary selection. They also found an "evolution-by-association," in which sequences near the regulatory segment showed greater mutational change -- as if they were "dragged along" with the evolving regulatory sequence.

In contrast, the researchers found that the DNA segment that coded for the PDYN protein itself -- as well as other sites spread around the genome -- showed evidence of "negative selection" that would preserve their original structure.

A key experiment, said Wray, was a laboratory demonstration that such regulatory mutations did have functional significance. When the researchers cultured human neural cells with either the human or chimpanzee regulatory PDYN segments, they found that the human segments caused the cells to produce more PDYN neuropeptide.

"So, these experiments told us that those mutations that we flagged by a statistical method as being likely to be under selection actually do something important in terms of function," said Wray. "The human version increases expression of the gene and production of prodynorphin, which is the direction of change we predicted."

The researchers also found evidence of evolutionary selection when they compared the regulatory sequences in people from different populations -- including those from Cameroon, China, Ethiopia, India, Italy and Papua New Guinea. Those analyses showed higher differences among the individual populations, but reduced variation within them. Such a pattern is a signature of evolutionary selection acting on the genetic sequence, said Wray.

Still mysterious, he said, is how the prodynorphin gene changes affect human neural development.

"All we can conclude now is that this gene is a very strong candidate for having a functional role in human evolution, and that its role probably has something to do with cognition. But beyond that, it's very hard to make a clear argument about specifically what that role is.

"We do know that not making enough prodynorphin causes clinical problems, but we don't know what having more of it did for us humans. We're hoping the clinical psychiatrists and psychologists can give us more insight into that aspect."

Wray and his colleagues have already identified a collection of some 250 other candidate genes -- mainly those active in the brain -- that they are beginning to analyze for evidence of evolutionary selection. They plan to perform the same basic analyses, in which they compare sequence information between humans and non-human primates for signatures of evolutionary selection.



Story Source:

The above story is based on materials provided by Duke University. Note: Materials may be edited for content and length.


Cite This Page:

Duke University. "Key Brain Regulatory Gene Shows Evolution In Humans." ScienceDaily. ScienceDaily, 12 December 2005. <www.sciencedaily.com/releases/2005/12/051212120211.htm>.
Duke University. (2005, December 12). Key Brain Regulatory Gene Shows Evolution In Humans. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2005/12/051212120211.htm
Duke University. "Key Brain Regulatory Gene Shows Evolution In Humans." ScienceDaily. www.sciencedaily.com/releases/2005/12/051212120211.htm (accessed October 25, 2014).

Share This



More Fossils & Ruins News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deep Sea 'mushroom' Could Be Early Branch on Tree of Life

Deep Sea 'mushroom' Could Be Early Branch on Tree of Life

Reuters - Innovations Video Online (Oct. 24, 2014) Miniature deep sea animals discovered off the Australian coast almost three decades ago are puzzling scientists, who say the organisms have proved impossible to categorise. Academics at the Natural History of Denmark have appealed to the world scientific community for help, saying that further information on Dendrogramma enigmatica and Dendrogramma discoides could answer key evolutionary questions. Jim Drury has more. Video provided by Reuters
Powered by NewsLook.com
Fossil Treasures at Risk in Morocco Desert Town

Fossil Treasures at Risk in Morocco Desert Town

AFP (Oct. 23, 2014) Hundreds of archeological jewels in and around the town of 30,000 people prompt geologists and archeologists to call the Erfoud area "the largest open air fossil museum in the world". Duration: 02:17 Video provided by AFP
Powered by NewsLook.com
Oldest Bone Ever Sequenced Shows Human/Neanderthal Mating

Oldest Bone Ever Sequenced Shows Human/Neanderthal Mating

Newsy (Oct. 23, 2014) A 45,000-year-old thighbone is showing when humans and neanderthals may have first interbred and revealing details about our origins. Video provided by Newsy
Powered by NewsLook.com
Weird-Looking Dinosaur Solves 50-Year-Old Mystery

Weird-Looking Dinosaur Solves 50-Year-Old Mystery

Newsy (Oct. 23, 2014) You've probably seen some weird-looking dinosaurs, but have you ever seen one this weird? It's worth a look. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins