Write your abstract here.Gene regulation, not just genes, is what sets humans apart from primates.
The
striking
differences between humans and chimps aren’t so much in the
genes we have, which are 99 percent the same, but in the way those
genes are used, according to new research from a Duke University team.
It’s rather like the same set of notes being played in very different ways.
In
two major traits that set humans apart from chimps and other primates –
those involving brains and diet – gene regulation, the complex
cross-talk that governs when genes are turned on and off, appears to be
significantly different.
“Positive
selection, the process by which genetic changes that aid survival and
reproduction spread throughout a species, has targeted the regulation
of many genes known to be involved in the brain and nervous system and
in nutrition,” said Ralph Haygood, a post-doctoral fellow in the
laboratory of Duke biology professor Gregory Wray.
Haygood
is lead author in a report on the research to be published online on
Sunday, Aug. 12, in the research journal Nature Genetics.
His
group looked at the
regulatory sequences immediately adjacent to 6,280
genes on the DNA of chimps, humans and the rhesus macaque, a more
distant primate relative that has 88 percent the same genes as humans.
These regulatory stretches of DNA are where proteins bind to the genome
to initiate a gene’s function. And it is here that evolution has
apparently fine-tuned the performance of genes, Wray said, resulting in
the dramatic differences in the human brain.
Though
many studies have looked for significant differences in the coding
regions of genes relating to neural system development and failed to
find any, the Duke team believes this is the first study to take a
genome-wide look at the evolution of regulatory sequences in different
organisms.
Other
studies have found significant differences between these species in the
coding regions that govern the immune system, the sense of smell and
the manufacture of sperm, but the coding regions of neural-related
genes had shown very little sign of positive selection in these
studies. Yet, as far back as 1975 when Mary-Claire King and Allan
Wilson first said humans and chimps were 99 percent the same
genetically, they had offered the suggestion that greater differences
might be found in the regulatory regions.
The
type of analysis performed by the Duke team couldn’t be done until the
macaque genome was published in 2005 because they needed a third,
closely related relative to compare the regulatory sequences.
The
mouse genome had been used as a reference point for comparing the
coding sequences of humans and chimps, but the non-coding sequences
have generally evolved much faster. “Mice wouldn’t work for analyzing
the non-coding sequences, because they’re too different from humans and
chimps,” Haygood said.
While
the biochemistry that cells use to turn food into energy is essentially
the same across most animal species, the fine-tuning of how an organism
deals with the different sorts of sugars and complex carbohydrates in
its diet lies in the regulatory sequences, Wray said.
Chimps
are fruit-eaters, for the most part, and would not last long away from
their fruit-rich forest. The sugars in their diet are relatively simple
to break down and convert to cellular fuel. Humans, on the other hand,
eat a wider array of foods, including many the chimps would simply not
be able to digest like starchy root crops. The researchers found
dramatic differences in the regulatory regions of their genes for
breaking down more complex carbohydrates. It may be that parts of the
human metabolism are cranked up to digest carbs down to simpler sugars.
“Regulatory
changes have adapted to changing circumstances without changing the
essential chemistry of metabolism,” Wray said. “This may set the stage
for a more focused analysis of the human diet.”
Much
is being written and hypothesized about how dietary changes have
contributed to the current human pandemics of obesity and diabetes, and
perhaps there will be some insights from understanding how these
regulatory sequences have evolved, he said.
To
do a genome-wide analysis of regulatory regions, Haygood and
post-doctoral fellow Olivier Fedrigo had to adapt some of the
statistical tools used for genome-wide analysis of coding regions. To
be sure their results would be robust, they focused on just the most
reliably accurate published DNA sequences in common between the three
animals, discarding two-thirds of the genome to ensure accuracy. “With
only three species, we had to be very stringent about quality,” Fedrigo
said.
The
researchers don’t think these findings will be of any help resolving
questions about how and when the ancestors of humans and chimps
diverged on the tree of life, but it’s safe to say that “most of this
is ancient history,” Wray said.
Source: Duke University