Yale Researchers Find 'Junk DNA' May Have Triggered Key Evolutionary Changes In

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Yale Researchers Find 'Junk DNA' May Have Triggered Key Evolutionary

Changes In Human Thumb And Foot

http://medicalnewscenter.com/out/out.cgi?

http://www.sciencedaily.com/releases/2008/09/080904145056.htm

Out of the 3 billion genetic letters that spell out the human genome,

Yale scientists have found a handful that may have contributed to the

evolutionary changes in human limbs that enabled us to manipulate

tools and walk upright.

Results from a comparative analysis of the human, chimpanzee, rhesus

macaque and other genomes reported in the journal Science suggest our

evolution may have been driven not only by sequence changes in genes,

but by changes in areas of the genome once thought of as " junk DNA. "

Those changes activated genes in primordial thumb and big toe in a

developing mouse embryo, the researchers found.

" Our study identifies a potential genetic contributor to fundamental

morphological differences between humans and apes, " said

Noonan, Assistant Professor of Genetics in the Yale University School

of Medicine and the senior author of the study.

Researchers have long suspected changes in gene expression

contributed to human evolution, but this had been difficult to study

until recently because most of the sequences that control genes had

not been identified. In the last several years, scientists have

discovered that non-coding regions of the genome, far from being

junk, contain thousands of regulatory elements that act as

genetic " switches " to turn genes on or off.

A rapidly evolving sequence from the human genome drives gene

activity in the developing thumb, wrist and ankle of mouse embryos,

suggesting the sequence may have contributed to key evolutionary

changes in the human limbs that allowed us to walk upright and use

tools.

An indication of their biological importance, many of these non-

coding sequences have remained similar, or " conserved, " even across

distantly related vertebrate species such as chickens and humans.

Recent functional studies suggest some of these " conserved non-coding

sequences " control the genes that direct human development.

In collaboration with scientists at Lawrence Berkeley National

Laboratory in California, the Genome Institute of Singapore, and the

Medical Research Council in the United Kingdom, Noonan searched the

vast non-coding regions of the human genome to identify gene

regulatory sequences whose function may have changed during the

evolution of humans from our ape-like ancestors.

Noonan and his colleagues looked for sequences with more base pairs

in humans than in other primates. The most rapidly evolving sequence

they identified, termed HACNS1, is highly conserved among vertebrate

species but has accumulated variations in 16 base pairs since the

divergence of humans and chimpanzees some 6 million years ago. This

was especially surprising, as the human and chimpanzee genomes are

extremely similar overall, Noonan said.

Using mouse embryos, Noonan and his collaborators examined how HACNS1

and its related sequences in chimpanzee and rhesus monkey regulated

gene expression during development. The human sequence activated

genes in the developing mouse limbs, in contrast to the chimpanzee

and rhesus sequences. Most intriguing for human evolution, the human

sequence drove expression at the base of the primordial thumb in the

forelimb and the great toe in the hind limb. The results provided

tantalizing, but researchers say preliminary, evidence that the

functional changes in HACNS1 may have contributed to adaptations in

the human ankle, foot, thumb and wrist-- critical advantages that

underlie the evolutionary success of our species.

However, Noonan stressed that it is still unknown whether HACNS1

causes changes in gene expression in human limb development or

whether HACNS1 would create human-like limb development if introduced

directly into the genome of a mouse.

" The long-term goal is to find many sequences like this and use the

mouse to model their effects on the evolution of human development, "

Noonan said.

National Institutes of Health and the U.S. Department of Energy

funded the work.