September 07, 2008
13 Genetic Letters Make Mice More Human

In our future we will create new species out of genetic pieces of existing species. Some of these species might some day challenge us for dominion over planet Earth. Scientists have discovered a very small piece of human DNA which causes a big change in embryonic development of limbs in mice.

WALNUT CREEK, Calif.— Subtle genetic changes that confer an evolutionary advantage upon a species, such as the dexterity characteristic of the human hand, while difficult to detect and even harder to reproduce in a model system, have nevertheless generated keen interest amongst evolutionary biologists. In findings published online in the September 5 edition of the journal Science, researchers from the U.S. Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) and their collaborators, have uncovered a specifically human 13-nucelotide change concealed in the vast three-billion-letter landscape of the human genome. Their experiments reveal this stretch of DNA to be a recently evolved regulator of gene expression that, when introduced into a mouse embryo system, influence the molecular machinery to yield human limb and thumb development patterns.

Some argue that genetic differences between humans are inconsequential because these differences make up such a small percentage of our total genome. But that a mere 13 genetic letters could cause mouse embryonic development to go down a pathway more like human limbs testifies to the power of small genetic sequences and small genetic differences. Also, that a group of scientists could fish this 13 letter sequence out of 2.9 billion letters in an entire human genome speaks to the power modern genetic analysis informed by an understanding of evolutionary theory.

The study reinforces the conclusion that certain regions of genomes—those which are conserved across many species over evolutionary time and do not encode genes—can have a powerful regulatory influence on gene expression or the production of proteins.

These scientists are looking for the genome differences that drove the split between primates and non-primates as well as the genetic differences that make humans unique from other primates in various ways. All these differences become candidates to stick into a transgenic dog or cat of course.

"The study points to how human nucleotide substitutions can alter the regulation of genes in humans distinct from that of non-human primates, such as chimps," said one of the study's corresponding/senior authors Eddy Rubin, Director of Berkeley Lab's Genomics Division and the U.S. Department of Energy Joint Genome Institute. "This highlights a strategy that could be applied across the genome to understand at a molecular level what leads to differences between humans and non-human primates."

These big comparisons between many species are made possible by the rapid decline in DNA sequencing costs. That decline is only going to continue. So the flood of data that makes cross-species comparisons possible will only increase as will the sophistication and power of the software and computers that do the comparisons. Therefore this discovery is just the opening of a flood gate. We will see many more such discoveries in the coming months and years.

Previously published work from the Rubin lab by co-authors Shyam Prabhakar (now at the Genome Institute of Singapore), James Noonan (now at the Yale University School of Medicine), and postdoctoral fellows describes a global survey they conducted of genomes—human, chimpanzee, rhesus macaque, mouse, rat, and dog. They screened across these species to find the most conserved regions, but where humans had many more changes relative to the others. By comparing the occurrence of these features, they were seeking to home in on evidence of positive selection—sequence changes that evolve more rapidly since the human and chimp paths split six million years ago.

The ability to do comparisons across species will also turn up genetic sequences in other species that give them features and capabilities that some humans will find appealing. Look at the people who go in for heavy plastic surgery, tattooing, and drug-enhanced muscle building. Imagine what those people will do once they can put genes into themselves from other species so that they can see better at night or hear better at high frequencies. If Fido and Rover can hear a dog whistle then why can't I?

Caveat: These results are preliminary. These scientists haven't proven that this short sequence really serves a role in humans similar to what it appears to do in mice.

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.

Share |      Randall Parker, 2008 September 07 11:44 AM  Evolutionary History


Comments
Tosha reisdorff said at July 24, 2014 8:57 PM:

What happened to the mouse embryos? were they destroyed or brought to term? Have the successfully reared mice with opposable thumbs?

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