Ancient swaths of DNA are a genomic puzzle that could lead to new therapies

At hundreds of spots in our DNA, there are ancient swaths that have remained puzzlingly unchanged over hundreds of millions of years of evolution. No one knows exactly what to make of these regions of DNA, called ultraconserved elements -- they don’t appear to serve essential functions, so why are they preserved?

“They are considered one of the most mysterious aspects of the genome,” Ting Wu, a Harvard Medical School geneticist, said at a talk at a genomics conference Wednesday in Cambridge.

But Wu has a provocative idea about these ultraconserved elements: Perhaps they are a natural defense system against harmful changes to our DNA. And perhaps there could be a way to harness this mechanism as a therapy, triggering it to cull cells that carry harmful genome rearrangements, before there is enough of a problem that a disease is even diagnosed.


Wu presented her talk, which she cautioned was speculative and a bit fanciful, at the “Explorers” session of the Genomes Environments Traits Conference. The annual meeting brings together volunteers in the Personal Genome Project, an experiment run by Harvard geneticist George Church in which participants have their genomes sequenced and share the data with the world to advance science.

At the meeting, a packed room of 100 participants learned about the latest in genome science and could take part in studies. For example, a box outside the session was designated for participants to deposit armpit swabs as part of one study.

Wu’s playful, daring, idea-generating presentation fed off the experimental mood of the crowd, providing a glimpse of a side of science that rarely is visible when results are presented. Scientific talks are usually designed as a straightforward presentation of evidence in support of one idea or another. The occasional joke is woven in, but the science often seems “done” by the time the presentation is made. Wu’s talk presented ideas still being formed and she freely admitted that the evidence is being accrued and may well turn out to debunk her own idea.


The idea that ultraconserved elements play a role in protecting the body against harm is based on the fact that people inherit two strands of DNA, one from each parent. When those strands are lined up next to each other, it would be obvious if there are aberrations in the ultraconserved areas -- a buckle would form in the strand. Wu thinks that when ultra conserved elements are working, the pairing may be a protective mechanism -- if the DNA goes awry at those spots, the cell dies.

So far, the idea that this is a process important for health is supported mainly by circumstantial evidence, but it may also explain what goes wrong in disease. For example, Wu said that her research has found that some types of cancer appear to stem from genome rearrangements found near ultra conserved elements, suggesting that preserving these stretches intact is important for health. Now, Wu’s lab is working on various approaches to understand and rigorously test the ideas.

She isn’t holding her breath to see her ideas confirmed: “We are fully prepared to be incorrect,” Wu said. Should that happen, the science may lead to something even more interesting.

Carolyn Y. Johnson can be reached at cjohnson@globe.com. Follow her on Twitter @carolynyjohnson.