Things are ripping right along for Whitehead’s Fungal Genome Initiative, thanks to the wrapping up of a two-year effort to sequence Neurospora crassa. And the insights scientists are reaping from this fungus, the common bread mold, are downright fascinating, if you ask institute computational biologist James Galagan.
Galagan, 34, joined Whitehead about four years ago after a wayward start in electrical engineering and computer science with Intel; he’s been working on the Neurospora project since it began. He made sure his team “reached out to the Neurospora community [to ask] anyone who was interested to join us.” That led to a collaboration across more than 30 organizations with some 70 scientists studying the 41 MB genome. “We would go over, topic by topic, what are the surprises we are finding,” Galagan says.
One of the most noteworthy was the characterization of a mechanism known as RIP, for repeat-induced point mutation. Galagan describes RIP as a process that acts during reproduction to detect duplicated sequences of more than about 400 base pairs with at least 80 percent nucleotide similarity. When it finds these regions, “RIP will mutate both copies by introducing point mutations — CG to TA mutations” to prevent duplicated sequence. Those sequences are also targets for methylation. “It’s a one-two punch against repetitive DNA,” Galagan says. “The duplicated genes get RIPped, and just to be safe, it silences them.”
Galagan and crew’s work is far from over. RIP may be interesting, but it leads to even more questions: how does Neurospora evolve, if not through duplicated genes? The last existing duplicated gene pairs in the genome are ancient, and probably came about before RIP itself evolved, Galagan posits. “RIP is preventing new genes from duplicating and serving as genes. Essentially, they get peppered with stop codons.” The mechanism is so thorough that “fully 98 percent of long repetitive sequences appear RIPped,” he adds. That leaves scientists looking into alternatives such as lateral gene transfer to explain how Neurospora evolved.
Now that Neurospora is making its own case for the importance of sequencing fungi, Galagan looks forward to “the opportunities for comparative genomics” as more and more fungi genomes are added to the books. “You can sequence them quickly and … get your head around the whole genome on a timeline that would be impossible for mammalian [genomes],” he says.