http://www.msnbc.msn.com/id/10466677/from/RL.2/

Geneticists find link to brain evolution
Regulatory mechanism for key protein is more active for humans

Updated: 1:03 p.m. ET Dec. 14, 2005

A gene known to be important for brain development is more active in
humans than in apes, a discovery that might have played a key role in
human evolution.

The gene is used by cells to make an opiatelike protein found in apes
and humans called "prodynorphin," or PDYN.

In humans, PDYN is believed to be important for perception, memory and
susceptibility to drug dependence. People who don’t make enough of the
protein are vulnerable to drug addiction, schizophrenia, bipolar
disorder and a form of epilepsy, studies have found.

"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," said Gregory Wray, a biologist at the Duke
University in North Carolina who was involved in the study.

The researchers found that humans possess a distinctive variant in a
regulatory segment of the gene that causes PDYN to be produced in higher
concentration than in apes.

Altering the regulatory segments of a gene is often a better way to
generate variability than altering the structure and function of a
protein through random mutations, Wray said.

Called "promoters," these regulatory segments determine how much and how
fast a protein is expressed rather than changing its structure or
function.

The finding supports a growing consensus among evolutionary
anthropologists that hominid divergence from the other great apes was
fueled not by the origin of new genes, but by the speeding up or slowing
down of the expression of existing genes.

In the studies, the researchers analyzed the sequence structure of the
PDYN promoter segment in humans and in seven species of nonhuman
primates: chimpanzees, bonobos, gorillas, orangutans, baboons,
pig-tailed macaques and rhesus monkeys.

The researchers didn’t find significant mutational changes in the parts
of the PDYN gene that controlled protein structure or function. Instead,
most of the changes were in segments of the gene that controlled the
regulation of PDYN. For example, the PDYN protein is identical in chimps
and humans, but the human version is 20 percent more active.

The researchers also found a surprisingly large amount of genetic
variation in the PDYN promoter segment among humans. The analyses showed
higher differences between the different populations—which included
Chinese, Papua New Guineans, (Asian) Indians, Ethiopians, Cameroonians,
Austrians and Italians — than within them. Such a pattern is a signature
of evolutionary selection, Wray said.

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

"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,"
Wray said. "We're hoping the clinical psychiatrists and psychologists
can give us more insight into that aspect."

The study was detailed in the December issue of PLoS Biology.

© 2006 LiveScience.com

http://www.msnbc.msn.com/id/10466677/from/RL.2/

Geneticists find link to brain evolution
Regulatory mechanism for key protein is more active for humans

Updated: 1:03 p.m. ET Dec. 14, 2005

A gene known to be important for brain development is more active in
humans than in apes, a discovery that might have played a key role in
human evolution.

The gene is used by cells to make an opiatelike protein found in apes
and humans called "prodynorphin," or PDYN.

In humans, PDYN is believed to be important for perception, memory and
susceptibility to drug dependence. People who don’t make enough of the
protein are vulnerable to drug addiction, schizophrenia, bipolar
disorder and a form of epilepsy, studies have found.

"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," said Gregory Wray, a biologist at the Duke
University in North Carolina who was involved in the study.

The researchers found that humans possess a distinctive variant in a
regulatory segment of the gene that causes PDYN to be produced in higher
concentration than in apes.

Altering the regulatory segments of a gene is often a better way to
generate variability than altering the structure and function of a
protein through random mutations, Wray said.

Called "promoters," these regulatory segments determine how much and how
fast a protein is expressed rather than changing its structure or
function.

The finding supports a growing consensus among evolutionary
anthropologists that hominid divergence from the other great apes was
fueled not by the origin of new genes, but by the speeding up or slowing
down of the expression of existing genes.

In the studies, the researchers analyzed the sequence structure of the
PDYN promoter segment in humans and in seven species of nonhuman
primates: chimpanzees, bonobos, gorillas, orangutans, baboons,
pig-tailed macaques and rhesus monkeys.

The researchers didn’t find significant mutational changes in the parts
of the PDYN gene that controlled protein structure or function. Instead,
most of the changes were in segments of the gene that controlled the
regulation of PDYN. For example, the PDYN protein is identical in chimps
and humans, but the human version is 20 percent more active.

The researchers also found a surprisingly large amount of genetic
variation in the PDYN promoter segment among humans. The analyses showed
higher differences between the different populations—which included
Chinese, Papua New Guineans, (Asian) Indians, Ethiopians, Cameroonians,
Austrians and Italians — than within them. Such a pattern is a signature
of evolutionary selection, Wray said.

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

"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,"
Wray said. "We're hoping the clinical psychiatrists and psychologists
can give us more insight into that aspect."

The study was detailed in the December issue of PLoS Biology.

© 2006 LiveScience.com

http://www.msnbc.msn.com/id/10466677/from/RL.2/

Geneticists find link to brain evolution
Regulatory mechanism for key protein is more active for humans