Strange things are afoot at the Biology of Genomes meeting at Cold Spring Harbor Laboratory in New York this week. When Jeramiah Smith, a geneticist at the University of Kentucky in Lexington delivered his talk this evening, he started by apologizing that what he was about to present was “kinda weird.”
Smith studies lampreys, ghastly looking jawless fish that hold a special place in the hearts of evolutionary biologists. Our common ancestor with these beasties resides somewhere deep within the Precambrian boughs of vertebrate ancestry.
Smith says he faced a puzzling problem with the lamprey genome, though. Some DNA sequence he had produced from lamprey sperm cells simply wasn’t lining up with the lamprey genome assembled by Sanger. Some bits aligned partially, and then veered off into unmatched DNA. Other bits were completely without a match. “That turned out to be a red herring in a sense,” he says. The sequence wasn’t lining up because up to about half a billion basepairs of DNA found in the reproductive cells of lampreys is deleted from all other adult cells.
Much of Smith’s work has since been trying to figure out both why and how the lamprey seems to make about 20% of its genome disappear during the development of all but its gametes.
Through sequencing DNA and RNA and comparing what he’s found with sequence from other animals, he’s identified a handful of genes that disappear at some point between fertilized egg and full grown fish. Among them, APOBEC1, some genes for zinc finger proteins and WNT7A/B. Several, said Smith, have qualities of “stem celly-ness”.
This makes sense. A fertilized egg would make good use of stem-cell-related genes as it divides and differentiates into all the cells of an adult organism. It also might make sense why the genes would be deleted. Genes that favour a stem-cell state also have a tendency to be oncogenic. Humans and other vertebrates have ways of tightly controlling the expression of such genes in adult cells to prevent cancers from occurring. But, asks Smith, “What better way to get rid of them,” than completely throwing them out?
A few other organisms also seem to delete genes in this way, including the only other known jawless vertebrate, the hagfish. And although the genetics of these species are definitely weird, Smith hopes that further study might make it clearer what’s going on and possibly help explain why other vertebrates, including humans, tend to do things differently. “I think it has something to tell us about the way our genes are regulated,” said Smith.