Researchers at K.U. Leuven and Harvard University show that stretches of DNA previously believed to be useless 'junk' DNA play a vital role in the evolution of our genome. They found that unstable pieces of junk DNA help tuning gene activity and enable organisms to quickly adapt to changes in their environments. The results will be published in the journal Science.

Junk DNA

"Most people do not realize that all our genes only comprise about 3% of the total human genome. The rest is basically one large black box," says Kevin Verstrepen, heading the research team. "Why do we have this DNA, what is it doing?"

Scientists used to believe that most of the DNA outside of genes, the so-called non-coding DNA, is useless trash that has sneaked into our genome and refuses to leave. One commonly known example of such 'junk DNA' are the so-called tandem repeats, short stretches of DNA that are repeated head-to-tail. "At first sight, it may seem unlikely that this stutter-DNA has any biological function," says Marcelo Vinces, one of the lead authors on the paper. "On the other hand, it seems hard to believe that nature would foster such a wasteful system."

Unstable repeats

The international team of scientists found that stretches of tandem repeats influence the activity of neighboring genes. The repeats determine how tightly the local DNA is wrapped around specific proteins called 'nucleosomes', and this packaging structure dictates to what extent genes can be activated. Interestingly, tandem repeats are very unstable -- the number of repeats changes frequently when the DNA is copied. These changes affect the local DNA packaging, which in turn alters gene activity. In this way, unstable junk DNA allows fast shifts in gene activity, which may allow organisms to tune the activity of genes to match changing environments -- a vital principle for survival in the endless evolutionary race.

Evolution in test tubes

To further test their theory, the researchers conducted a complex experiment aimed at mimicking biological evolution, using yeast cells as Darwinian guinea pigs. Their results show that when a repeat is present near a gene, it is possible to select yeast mutants that show vastly increased activity of this gene. However, when the repeat region was removed, this fast evolution was impossible. "If this was the real world," the researchers say, "only cells with the repeats would be able to swiftly adapt to changes, thereby beating their repeat-less counterparts in the game of evolution. Their junk DNA saved their lives."

The research has been funded by Human Frontier Science Program, Fund for Scientific Research Flanders, NIH, K.U. Leuven and VIB (the Flanders Institute for Biotechnology).

Source: Science Daily

In what could be a major pharmaceutical breakthrough, research published in The FASEB Journal describes how scientists from St George's, University of London have devised a one-two punch to stop HIV. First the report describes a new protein that can kill the virus when used as a microbicide. Then the report shows how it might be possible to manufacture this protein in quantities large enough to make it affordable for people in developing countries.

"We desperately need to control the spread of HIV, particularly in developing countries," said Julian Ma of the Department of Cellular and Molecular Medicine at St. George's and the senior researcher involved in the work. "A vaccine is still some way off, but microbicides could provide a more immediate solution, provided we can overcome major hurdles of high efficacy, low cost, and wide availability—all of which we address in this study."

In the research paper, Ma and colleagues describe how they combined two protein microbicides (b12 monoclonal antibody and cyanovirin-N) into a single "fusion" molecule and showed that this molecule is more active against HIV than either of its individual components. They designed synthetic DNA for producing this molecule and introduced this DNA into plant cells. After regenerating transgenic plants that produce the fusion molecule, they prepared the microbicide from a plant extract made by grinding the leaves.

"This study is nothing short of a breakthrough—not only does it yield a new drug to fight the spread of HIV, but it also shows us how we can produce it on the scale necessary to get it into the hands of those who need it most," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "Unlike their unregulated counterparts in the dietary supplement industry, these scientists are using the engines of nature to manufacture pharmaceuticals that must undergo extensive safety and efficacy testing long before the first gel or cream is administered."

Source: Science Daily

Mice carrying a "humanized version" of a gene believed to influence speech and language may not actually talk, but they nonetheless do have a lot to say about our evolutionary past, according to a report in the May 29th issue of the journal Cell, a Cell Press publication.

"In the last decade or so, we've come to realize that the mouse is really similar to humans," said Wolfgang Enard of the Max-Planck Institute for Evolutionary Anthropology. "The genes are essentially the same and they also work similarly." Because of that, scientists have learned a tremendous amount about the biology of human diseases by studying mice.

"With this study, we get the first glimpse that mice can be used to study not only disease, but also our own history."

Enard said his team is generally interested in the genomic differences that set humans apart from their primate relatives. One important difference between humans and chimpanzees they have studied are two amino acid substitutions in FOXP2. Those changes became fixed after the human lineage split from chimpanzees and earlier studies have yielded evidence that the gene underwent positive selection. That evolutionary change is thought to reflect selection for some important aspects of speech and language.

"Changes in FOXP2 occurred over the course of human evolution and are the best candidates for genetic changes that might explain why we can speak," Enard said. "The challenge is to study it functionally."

For obvious reasons, the genetic studies needed to sort that out can't be completed in humans or chimpanzees, he said. In the new study, the researchers introduced those substitutions into the FOXP2 gene of mice. They note that the mouse version of the gene is essentially identical to that of chimps, making it a reasonable model for the ancestral human version.

Mice with the human FOXP2 show changes in brain circuits that have previously been linked to human speech, the new research shows. Intriguingly enough, the genetically altered mouse pups also have qualitative differences in ultrasonic vocalizations they use when placed outside the comfort of their mothers' nests. But, Enard says, not enough is known about mouse communication to read too much yet into what exactly those changes might mean.

Although FoxP2 is active in many other tissues of the body, the altered version did not appear to have other effects on the mice, which appeared to be generally healthy.

Those differences offer a window into the evolution of speech and language capacity in the human brain. They said it will now be important to further explore the mechanistic basis of the gene's effects and their possible relationship to characteristics that differ between humans and apes.

"Currently, one can only speculate about the role these effects may have played during human evolution," they wrote. "However, since patients that carry one nonfunctional FOXP2 allele show impairments in the timing and sequencing of orofacial movements, one possibility is that the amino acid substitutions in FOXP2 contributed to an increased fine-tuning of motor control necessary for articulation, i.e., the unique human capacity to learn and coordinate the muscle movements in lungs, larynx, tongue and lips that are necessary for speech. We are confident that concerted studies of mice, humans and other primates will eventually clarify if this is the case."

Source: Science Daily