March 10, 2011

Research Shows Missing DNA Makes Us Human

Scientists have analyzed the genomes of humans and closely related primates and discovered over 500 regulatory regions that chimpanzees and mammals have that humans do not. 

Gill Bejerano, a biologist at Stanford University School of Medicine, and colleagues found that humans lack the penile spines found in many other mammals, and also why specific regions of human brains are larger than those of our closest relatives.

"Rather than looking for species-specific differences in specific genes or genomic regions that exist in humans, we asked, 'Are there functional, highly conserved genetic elements in the chimpanzee genome that are completely missing in humans?" Bejerano said in a statement.

"We found several hundred locations that, as far as we could see, are absent in our species alone." Until now, many evolutionary geneticists focused on differences among genes, rather than the regulatory regions outside the genes."

Researchers said that losing small pieces of regulatory DNA means that the related changes are likely to be subtle: Although the location or the timing of the expression of the gene within the body may change, the gene product itself remains functional.

The distinction of these genes leads to viable differences among individuals that can eventually lead to the development of new traits and species, according to the researchers.

"It's not only unusual, but also particularly interesting, to find these sequences missing in humans," David Kingsley, PhD, professor of developmental biology, said in a statement. "These are the same type of molecular events that have been shown to produce evolutionary differences among other organisms."

Kingsley's previous research focused on understanding how similar genetic changes over time have led to body modifications in the small fish that allow it to live in many different environments.

"In fish, we find that the loss of regulatory DNA has produced key evolutionary differences in body structures," Kingsley said. "The current study not only identifies an intriguing list of deletions in humans, but also links particular deletions with specific anatomical changes that are unique to the human lineage."

The researchers found that one of the missing regions normally drives the expression of the androgen receptor in sensory whiskers and genitalia. 

Androgen is a sex hormone responsible for growth of sensory hairs and surface spines found on the penises of many mammals.

Losing these structures in humans decreases tactile sensitivity and increases the duration of intercourse in humans relative to other species.

Another region was adjacent to a tumor suppressor gene that suppresses neural growth in a particular part of the brain. 

The scientists said that the resulting changes may have paved the way for monogamous pair-bonding and the complex social structure necessary to raise our species' relatively helpless infants.

The researchers wrote in the journal Nature that there are many other human-specific deletions to investigate.  The scientists are encouraging their lab members to study the functions of other interesting regions.

"Finding these sorts of human-specific changes is also a good motivator to look at other genomic events," Bejerano said in a press release.

"Previous work in my lab has shown that many thousands of DNA regions are highly conserved among mammals, and almost never lost during evolution. Much of my lab is devoted to understanding what these regions do. Now we are starting to learn what can happen when they are lost."


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