November 17, 2007


Are “Ultraconserved” Genetic Elements Really Indispensable? (Liza Gross, 9/04/07, PLoS Biol)

With over 180 genomes sequenced to date and counting, researchers must rely on certain assumptions to help them sift through mountains of data and identify the most promising candidates for functional analysis. One of the guiding principles of comparative genome analysis assumes that highly conserved DNA sequences—which show little variation across species—have been preserved throughout evolution because they encompass important biological functions.

In 2004, researchers identified a unique category of long sequences (spanning at least 200 DNA base pairs) in the human genome that are exactly the same in the mouse and rat. Though over half of these “ultraconserved” genetic elements don't code for gene products, their concentration near coding regions (for transcription factors and molecules involved in developmental processes), along with some experimental evidence, suggests that they may play a role in gene regulation. The discovery of ultraconserved sequences stimulated vigorous debate about the mechanisms that may have led to such mutational restraint. It also provided an unprecedented opportunity to test the conventional wisdom that these sequences encode fundamental functions—how else to explain their perfect preservation over the 80 million or so years since the rodent and primate lineages diverged?

In a new study, researchers at the Joint Genome Institute and Lawrence Berkeley National Laboratory used standard transgenic techniques to test these long-held assumptions, with unexpected results. Nadav Ahituv, Len Pennacchio, Edward Rubin, and colleagues reasoned that if ultraconserved elements are as vital as predicted by theory, then deleting them from an animal should cause severe abnormalities that result in infertility or death. To their surprise, the researchers found that all of the mice tested not only survived these expected lethal deletions but did so with no apparent observable effect (or phenotype).

What would be really newsworthy is if any of their guiding principles ever turned out to be right.

Posted by Orrin Judd at November 17, 2007 9:45 PM

80 million years is a long time to keep useless junk in the genetic attic. God must be one helluva packrat.

Posted by: ghostcat at November 17, 2007 11:46 PM

The guiding principles of modern biology actually have a pretty track record over the last century, though you'd never know it from what gets written around here. As for comparative genome analysis, well, it is a rather new discipline. It's no surprise if their guiding principles need some more work.

My criticism is that it's a bit like cutting a random hose in the engine compartment of your car, driving around the block, and then claiming that proves the hose is pointless. Sure, wiseguy, just drive it like that for a month and get back to me. That point is somewhat addressed at the end of the piece.

Posted by: PapayaSF at November 18, 2007 12:03 AM

Maybe nature knew those genes would be needed someday for rats to turn into humans.

Posted by: Randall Voth at November 18, 2007 7:25 AM