News

You say genome editing, I say natural mutation

A Cold Spring Harbor Laboratory plant geneticist and computational biologist teamed up to decipher the unpredictability of natural and engineered mutations in tomatoes
Luis Sandoval
By Luis Sandoval
Oct. 28, 2023

For tens of thousands of years, evolution shaped tomatoes through natural mutations. Then, humans came along. For centuries, we’ve bred and cherry-picked tomatoes with our preferred traits. Today, CRISPR genome editing allows us to make new crop mutations that improve traits even further. However, individual mutations, whether natural or engineered, don’t work alone. Each operates in a sea of thousands of so-called “background” mutations. These changes have been sowed by evolution and agricultural history. And what if just one could dramatically alter the desired outcome of an engineered mutation?

Now, a plant geneticist and a computational scientist at Cold Spring Harbor Laboratory have teamed up to explore just how predictable plant breeding actually is with natural and CRISPR mutations. To do so, they turned back the evolutionary clock.

CSHL Professor and HHMI investigator Zachary Lippman and Associate Professor David McCandlish wondered if different natural and engineered mutations could have similar effects on tomato size depending on the presence of two other gene mutations. Using CRISPR, they created a series of mutations in the SlCLV3 gene. (Natural mutation of this gene is known to increase fruit size.) They then combined those mutations with others in genes that work with SlCLV3.

A collection of tomatoes with different combinations of artificial and natural mutations. The mutations affected the number of locules, or seed pockets, resulting in different fruit sizes. Lyndsey Aguirre, a CSHL School of Biological Sciences graduate, led the project.
A collection of tomatoes with different combinations of artificial and natural mutations. The mutations affected the number of locules, or seed pockets, resulting in different fruit sizes. Lyndsey Aguirre, a CSHL School of Biological Sciences graduate, led the project.

Altogether, they created 46 tomato strains with different combinations of mutations. They found the SlCLV3 mutations produced more predictable effects when certain other mutations were also present. Mutations in one gene produced predictable changes in tomato size, but mutations in another yielded random outcomes. Remarkably, the most beneficial effect involved two mutations that arose millennia ago and were central in tomato domestication.

New research by McCandlish and Lippman may help us better understand genetic predictability. But one thing’s certain. Context matters when introducing new crop mutations. Lippman explains:

“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.”

Lippman and McCandlish’s work suggests the role of background mutations demands reassessment. “The field will have to grapple with this as we start to make more highly engineered organisms,” says McCandlish. “Once you start making 10, 20 mutations, the probability of having unanticipated results may increase.”

The book of evolution has been written in all different languages, many of which we’re still learning. Plant genetics and computational biology offer two means of deciphering the text. Lippman and McCandlish hope their collaborative interpretation will help science meet the challenge. Looking ahead, it may also help humanity adapt crops to meet the ever-evolving needs of society.

This article was first published by Cold Spring Harbor Laboratory. Read the original.

Enjoy reading ASBMB Today?

Become a member to receive the print edition monthly and the digital edition weekly.

Learn more
Luis Sandoval
Luis Sandoval

Luis Sandoval is a communications specialist at Cold Spring Harbor Laboratory. He writes about science research, education and outreach for the CSHL Newsstand.

 

Related articles

From the journals: February 2019
Gelareh (Abulwerdi) Vinueza, Kerri Beth Boggs & Sasha Mushegian
From the journals: November 2018
Gelareh (Abulwerdi) Vinueza, Sasha Mushegian, Laurel Oldach & Kerri Beth Boggs

Get the latest from ASBMB Today

Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.

Latest in Science

Science highlights or most popular articles

Iron could be key to treating a global parasitic disease
Journal News

Iron could be key to treating a global parasitic disease

April 16, 2024

A study has found that leishmaniasis causes body-wide changes in iron balance, leading to red blood cell damage.

Environmental DNA is everywhere
News

Environmental DNA is everywhere

April 14, 2024

The ability to extract trace bits of DNA from soil, water, and even air is revolutionizing science. Are there pitfalls?

Early COVID-19 research is riddled with poor methods and low-quality results
News

Early COVID-19 research is riddled with poor methods and low-quality results

April 13, 2024

The pandemic worsened, but didn’t create, this problem for science.

From the journals: MCP
Journal News

From the journals: MCP

April 12, 2024

Three views of mass spec: analyzing secreted protein spectra, imaging mass spectrometry for clinical use and spectral libraries for MS data analysis. Read about these recent papers.

Understanding the fat science
Journal News

Understanding the fat science

April 9, 2024

Researchers at UCLA investigate lipid remodeling in the liver for energy generation.

No oxygen? No problem
Journal News

No oxygen? No problem

April 8, 2024

By studying how electric fish survive in hypoxic streams for months at time, researchers may find new ways to target tumors.