Unraveling Tomato’s Genetic Mysteries: How Background Mutations Alter Outcomes

Exploring Tomato’s Genetic Enigma: How Historical Mutations Shape Outcomes

Throughout millennia, tomatoes have undergone natural genetic mutations driven by the forces of evolution, with humans later intervening to selectively breed for desired traits. In our contemporary era, the advent of CRISPR genome editing has afforded us unprecedented precision in altering tomato genetics. Researchers at Cold Spring Harbor Laboratory embarked on a study to investigate the predictability of breeding tomatoes, taking into account both naturally occurring mutations and those induced by CRISPR technology. Their findings underscore a crucial revelation: the presence of “background” mutations stemming from the long history of evolution and agriculture can exert significant influence on the results of engineered mutations. This highlights the imperative need to comprehensively grasp and consider these background mutations when introducing novel genetic modifications.

Over countless millennia, the process of evolution has left an indelible mark on tomatoes, instigating spontaneous genetic variations. Subsequently, as humans took the reins, they dedicated centuries to the meticulous breeding of tomatoes, meticulously choosing traits that met their preferences. Presently, CRISPR genome editing empowers us to effectuate crop mutations that further enhance these traits. Nevertheless, it is essential to recognize that individual mutations, whether naturally occurring or artificially induced, do not function in isolation.

Each mutation operates within a complex milieu characterized by thousands of concurrent “background” mutations, which have been imprinted upon the tomato genome by the lengthy course of evolution and agricultural practices. Consider for a moment the prospect that merely one of these background mutations could drastically reshape the intended outcome of an engineered genetic alteration.

Exploring Predictability in Tomato Genetics

To delve into the actual predictability of plant breeding, a plant geneticist and a computational scientist at Cold Spring Harbor Laboratory, namely CSHL Professor & HHMI Investigator Zachary Lippman and Associate Professor David McCandlish, embarked on an intriguing experiment. Their aim was to scrutinize whether distinct natural and engineered mutations could yield comparable effects in terms of tomato size contingent upon the presence of two additional gene mutations. Employing CRISPR technology, they initiated a series of mutations in the SlCLV3 gene, known for its capacity to augment fruit size. These mutations were then amalgamated with mutations occurring in other genes that collaborate with SlCLV3.

The outcome was the creation of 46 tomato strains featuring various permutations of mutations. The researchers discerned that the SlCLV3 mutations produced more predictable effects when specific other mutations coexisted. Notably, mutations in one gene yielded consistent alterations in tomato size, while mutations in another led to unpredictable outcomes. Remarkably, the most advantageous results were attained through the collaboration of two mutations that had originated millennia ago and played pivotal roles in the domestication of tomatoes.

Implications for Genome Editing

The research undertaken by McCandlish and Lippman not only contributes to our understanding of genetic predictability but also underscores a critical point: the context within which new crop mutations are introduced is of paramount importance. Zachary Lippman elucidates this by stating, “Is genome editing a means to expeditiously bring about consumer benefits such as enhanced flavor and nutrition? The answer is likely affirmative. The crux of the matter lies in assessing its predictability.”

In light of their work, Lippman and McCandlish prompt us to reevaluate the role of background mutations, particularly as we venture into the realm of crafting highly engineered organisms. McCandlish emphasizes, “As we embark on the path of creating organisms with 10, 20 mutations, the likelihood of encountering unforeseen consequences may rise.”

Deciphering the Genetic Chronicles of Evolution

The saga of evolution has been transcribed in a multitude of languages, many of which remain a subject of ongoing study. Plant genetics and computational biology provide us with two potent tools for decoding this narrative. Through their collaborative interpretation, Lippman and McCandlish aspire to aid the scientific community in meeting this challenge. Looking ahead, their research could also serve to equip humanity with the capacity to tailor crops to meet the ever-evolving demands of society.

Reference: “Idiosyncratic and dose-dependent epistasis drives variation in tomato fruit size” by Lyndsey Aguirre, Anat Hendelman, Samuel F. Hutton, David M. McCandlish and Zachary B. Lippman, 19 October 2023, Science.
DOI: 10.1126/science.adi5222

This study received financial support from the National Science Foundation, the Hearst Foundations, the National Institutes of Health, the Alfred P. Sloan Foundation, and the Howard Hughes Medical Institute.

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More about Tomato Genetic Mutations

• Cold Spring Harbor Laboratory
• CRISPR genome editing
• Tomato genetics
• Genetic mutations in crops
• Background mutations in genetics
• Zachary Lippman’s research
• David McCandlish’s research
• Genome editing and agriculture
• National Science Foundation
• Hearst Foundations
• National Institutes of Health
• Alfred P. Sloan Foundation
• Howard Hughes Medical Institute