For millennia, tomatoes have undergone evolution through natural mutations, later enhanced by human intervention selecting for preferred traits. The modern CRISPR genome editing method permits the creation of specific crop mutations to further enhance these traits. But it's crucial to remember that these mutations don't function in isolation. They exist alongside thousands of "background" mutations, brought about by evolution and farming practices, any of which could impact the result of a new mutation.
Plant geneticist Zachary Lippman and computational scientist David McCandlish at Cold Spring Harbor Laboratory (CSHL) collaborated to investigate the predictability of plant breeding with both natural and CRISPR-induced mutations. Their methodology hinged on a form of reverse engineering: turning back the evolutionary clock.
Lippman and McCandlish probed the possibility that distinct mutations, both natural and engineered, might influence tomato size in a similar manner, contingent on two other gene mutations. They employed CRISPR to induce a range of mutations in the SlCLV3 gene, which, when naturally mutated, is known to augment fruit size. These mutations were then paired with other alterations in genes that operate in tandem with SlCLV3.
In their study, the duo developed 46 tomato strains, each with unique mutation combinations. Their findings showed that SlCLV3 mutations had more consistent impacts when certain other mutations were also present. Changes in one specific gene led to foreseeable shifts in tomato size, while another gene's mutations resulted in unpredictable outcomes. Intriguingly, the most advantageous effect was tied to two mutations that emerged thousands of years ago, playing a vital role in tomato domestication.
This research by McCandlish and Lippman provides insights into genetic predictability. Lippman emphasized the potential benefits of genome editing for consumers in terms of taste and nutrition, while also pondering its predictability. He said, “Is genome editing a way to quickly bring in consumer benefits—better flavor, nutrition? The answer is probably yes. The question is how predictable is it going to be.”
The duo's study indicates that the influence of background mutations needs reevaluation. McCandlish expressed his concerns, stating, “The field will have to grapple with this as we start to make more highly engineered organisms. Once you start making 10, 20 mutations, the probability of having unanticipated results may increase.”
Both plant genetics and computational biology serve as tools to interpret the intricate narrative of evolution. Through their combined efforts, Lippman and McCandlish aim to assist science in facing this monumental task and possibly aiding humanity in modifying crops to cater to the ever-changing requirements of society.
Read the full study published in Science.