MADISON — Late blight caused the 19th century famine that sparked a wave of emigration from Ireland to the United States, but the disease has also infected tomatoes and potatoes this year. Potatoes, the world’s fourth-largest food crop, were raised on 65,500 acres in Wisconsin in 2007. If a potato field is not treated with pesticide, late blight can destroy the crop in a few days.
This week (Sept. 9), the online edition of the scientific journal Nature will report on the full genetic sequence, or genome, of Phytophthora infestans, the cause of late blight. The genome resulted from a large international effort, which benefited from significant contributions from scientists at the University of Wisconsin-Madison, to understand the genetics of a plant disease that has evaded many control efforts.
“This pathogen has an exquisite ability to adapt and change, and that’s what makes it so dangerous,” says senior author Chad Nusbaum, co-director of the Genome Sequencing and Analysis Program at the Broad Institute of MIT and Harvard, which directed the sequencing project.
About 75 percent of the genome contains repetitious DNA, which is now seen as key to understanding late blight’s destructive potential, Nusbaum adds. “We now have a comprehensive view of its genome, revealing the unusual properties that drive its remarkable adaptability. Hopefully, this knowledge can foster novel approaches to diagnose and respond to outbreaks.”
To cope with the confusing level of repetition, Broad Institute researchers contacted David Schwartz, a professor of chemistry and genetics at UW-Madison. Schwartz was the principal inventor of the “optical mapping” system, which uniquely complements the traditional, letter-by-letter approach to gene sequencing.
The DNA of late blight contains about 240 million sub-units, or “bases.” To efficiently identify these units, scientists first cut the DNA into shorter chunks, and later digitally reassemble the chunks into one long sequence. But traditional sequencing technology gets confused by genomes that contain so much repetition, Schwartz says.
The advantage of optical mapping can be seen by comparison to digital maps, Schwartz says. “In a digital map; you can see the streets; like optical mapping, this is a medium-resolution picture of the subject. Then you can switch to a high-resolution street view. You can count windows in the houses, but it’s hard to see how the houses fit together. It’s the same with traditional gene sequencing: You get a much higher resolution view, but it’s harder to know where the units are located.”
Optical mapping was particularly helpful with the nettlesome genome of late blight, Schwartz adds. “It’s full of repeated DNA sequences, so all the windows look the same and it’s hard to know where the house should go. Combining the letter-by-letter information from sequencing with the broader view from optical mapping allowed us to put the genome together.”
The DNA chunks that used optical mapping “are much longer than those used in traditional sequencing and mapping, which means we can span lots of gaps that others cannot,” adds Shiguo Zhou, Schwartz’s colleague in the Laboratory for Molecular and Computational Genomics and the principal scientist constructing the map. “We can characterize regions where you see the same code repeated over and over and put whole genome together.”
The study found that the late blight genome is two and a half to four times larger than those of its relatives, mainly due to a massive amount of repetitive DNA. Although these repetitive regions contain only a few genes, they are specialized for attacking plants, so understanding the repetitions may help explain why late blight is such an effective plant pathogen.
The research group hopes that further exploration of the genome will reveal weak links in the organism’s offensive strategy. According to co-lead author Brian Haas of the Broad Institute, “The repeat-rich regions change rapidly over time, acting as a kind of incubator to enable the rapid birth and death of genes that are key to plant infection. As a result, these critical genes may be gained and lost so rapidly that the hosts simply can’t keep up.”