The set of genes known to have been under selective pressure during primate evolution has gained another member: Prodynorphin. Regulatory regions for prodynorphin, an important brain gene, have been under natural selective pressure during evolution from lower primates to humans.

Durham, N.C. -- 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.

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.

I think they are exaggerating to call PDYN "this first evolutionarily selected gene". See my discussion below of Microcephalin, ASPM, and the Ashkenazi Jewish genetic disease genes such as the sphingolipid pathway genes.

Prodynorphin is involved in many brain functions.

The researchers published their findings in an article 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.

Note how the study of gene sequence variations from an evolutionary perspective allows scientists to find what areas most likely changed to make human minds different than the minds of other primates. The theory of evolution is not just an explanation of ancient events. Genetic models of evolution help in doing practical research in how the brain works.

"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.

The identification of areas of the genome which were under active selective pressure in evolution helps the search for genetic sequence variations which boost intelligence in the smarter folks among us. Areas of brain genes which are shown to be under recent selective pressure are the areas most likely to contain genetic variations that account for the huge range of intellectual ability found in the human population.

The report above about PDYN reminds me of previous reports about the brain gene ASPM. First Bruce Lahn of the University of Chicago found that ASPM underwent extended selective pressure and change in the primates. Then Lahn showed that ASPM and Microcephalin have been under strong selective pressure in recent human history and the genetic variations recently selected for were not selected for equally in all human populations. PDYN is basically at the research stage that ASPM was at before Lahn compared large numbers of humans for their ASPM variations. The next logical step with PDYN would be to compare regulatory regions for that gene in different human populations to see if they differ in their frequency of different genetic variations.

ASPM, PDYN, and Microcephalin make excellent candidates for genes whose variations cause differences in levels of intelligence. What we need is a massive study of people who would get IQ tested and also get genetically tested for which variations they have for these genes and for the regulatory regions for these genes. A number of other genes would also make good candidates for inclusion in such a study. as Greg Cochran, Henry Harpending, and Jason Hardy have recently demonstrated the genes which cause Jewish genetic diseases are also excellent candidates for comparisons of genetic sequences and IQ levels.

The Duke University researchers in the report at the top of this post have 250 more genes active in the brain they are going to look at for signs of natural selective pressures for brain evolution. My guess is that in the next 5 years the evolutionary approach to brain gene study is going to lead to the identification of many genetic variations that causes differences in intelligence. The work could go much faster if the genetic basis for IQ differences was not so taboo politically. But enough excellent work is getting done in this area that I'm hopeful about some major discoveries in spite of the taboo.

The discovery of genetic variations which boost IQ will lay the groundwork for attempts to boost human intelligence. People will use genetic tests to choose mates and choose egg and sperm donors to get smarter offspring. Also, the knowledge that up and down regulation of specific genes affectgs intelligence levels will lead to attempts to develop drugs which change the regulation of those genes in hopes of boosting intelligence. So the search for signs of selective pressures on brain genes will lead to IQ boosts that will eventually cause revolutionary changes in human societies.