Typos and Scotch Tape
Improvement of Orphan Crops With CRISPR-Cas9
If I misspell a word when typing, I hit backspace. If I misspell a word in pencil, I erase; in pen, I use white-out. I type about 450 characters per minute, a rate of eight characters per second, with 98% accuracy. If I transcribe text for 10 minutes, I will have to fix 90 mistakes. Cells are typists, too. While living things grow, their cells transcribe DNA at rates up to 1,000 characters per second. Cells are much more accurate than I am, but they still make typos. Though cells almost always fix their typos, there are minute differences between everyone, even identical twins. We all operate in a unique way. Because we are different from each other, we survive and thrive over time.
Ten thousand years ago, our ancestors first planted seeds, comparing the products of their labor and replanting the best of the crop. The biggest tomatoes. The least bitter broccoli. The corn that grew straight instead of sprawling. We domesticated crops like these to the same extent we domesticated our pets: we have Great Dane tomatoes, and we have Chihuahua tomatoes. The cutting edge of our understanding of genetics has always been crop breeding. As we learned to link an advantageous plant characteristic to a difference in its DNA, our major commercial crops benefited. Other crops less common in the American supermarket, such as breadfruit, mungbean, or taro, have not had the same degree of effort spent breeding them to be well-behaved. These “orphan crops” are often staples in Africa, Asia, or South America. They offer nutritional advantages and economic value to their communities.
Organizations like the African Orphan Crops Consortium strive to improve these crops by generating DNA resources, local expertise, and breeding infrastructure. Breeding requires time and a diversity of differences to choose from. The time a plant takes to grow is an inflexible constraint, but we can foster diversity by causing deliberate typos. All major commercial crop improvement uses this strategy. The techniques that trigger typos cause thousands of typos in a single plant. In subsequent generations, we narrow the plants down to one typo that causes a difference we like. These tried and true techniques are being used to improve orphan crops, but the traditional process is time-consuming and expensive while the need for improved crops is pressing.
Researchers could now shrink the time required if they leverage their knowledge about commercial crops with a more precise tool — CRISPR-Cas9.
CRISPR-Cas9 is one of several “gene editing” technologies. Remember: DNA is a series of letters. These letters arrange in patterns that form words. Read together, the words become sentences, paragraphs, novels. They convey information. Imagine a plant’s genetic information as the text of Pride and Prejudice. On first page, where it reads, “It is a truth universally acknowledged, that a single man in possession of a good fortune, must be in want of a wife,” picture ripping the page in two through the word “good.” Then, tape the halves back together. Depending on your alignment skills, the single man may be in possession of a good fortune, a god fortune, or maybe a ood fortune. CRISPR-Cas9 is a search engine attached to scissors: it find a sentence in DNA and cuts it. The cell tapes the break back together but not always perfectly, and the imperfect typo, like Mr. Darcy’s ood fortune, changes what the DNA means. CRISPR-Cas9 enables scientists to target a particular piece of DNA, but the cell’s Scotch tape determines if an edit is made.
Take, for example, the groundcherry, a relative of tomato native to Mexico and Central America. Its fruits taste good but are the size of a fingernail, and it has many long side branches that produce few fruit. At one time, tomato had similarly smaller fruits and weedier growth. We know which changes in tomato DNA correlate with bigger fruit and more compact plants. Because groundcherry and tomato are relatives, their DNA is similar. Researchers at Cold Spring Harbor Laboratory wondered if altering the groundcherry DNA related to the tomato DNA would mimic the effects on tomato. With CRISPR-Cas9, they cut precise sentences of groundcherry DNA based on their knowledge of tomato. One edit made the groundcherry plants smaller and compact. Their side branches bore more fruit. With a different edit, fruits grew 24% larger. Researchers created a shortcut to groundcherry domestication by mimicking tomato domestication.
This approach will not work for every orphan crop as the chosen edits rely on inferences from the genetics of well-studied plants. Groundcherry and tomato are first cousins, but another pairing of an orphan crop and a well-studied plant may be fourth cousins twice-removed. Their DNA would be less similar. The technology is also imperfect. CRISPR-Cas9’s search engine is simple to program but not always 100% accurate. It finds and cuts the sentence searched and similar sentences, which alters DNA researchers want to leave alone. The undesired, “off-target” typos caused by CRISPR are less numerous than typos caused by traditional techniques, so breeders’ reliable strategies to eliminate undesired typos will be less time-consuming and expensive. However, researchers must download the CRISPR-Cas9 search engine onto a plant for it to work, and different plants run incompatible browsers.
Many people are nervous, too, about handing scientists scissors to change their food. Scissors should be held pointed down. You shouldn’t run with them. Scientists must demonstrate proper scissor protocol when they use these techniques. The balancing act between innovation and safety requires trust between scientists and consumers. Without it, innovation is useless, and safety is stifling.
Since we first shoved a seed into the ground to see if it grew, we’ve looked for a plant’s typos. Humans have been plant geneticists for 10,000 years. We learned to read a plant’s DNA, and that skill improved our tomatoes and corn. Improving orphan crops will help the communities that grow them. We should use all the best techniques we have available to achieve that goal as long as scientists continue not to run with the scissors.
African Orphan Crops Consortium: http://africanorphancrops.org/
"Rapid improvement of domestication traits in an orphan crop by genome editing," Z. Lemmonn et al, 2018. Nature Plants