Yeast has more than 50% of its DNA recreated – 11/13/2023 – Science

An international team of scientists has already completed more than half of the work needed to create a “genome 2.0” – the entirety of a complex organism’s DNA, assembled from scratch in the laboratory and organized according to researchers’ intentions, rather than following the somewhat messy patterns that nature has adopted over billions of years.

For now, the synthetic genome is being created for a species of microorganism, yeast Saccharomyces cerevisiae. This member of the fungi group is used, for example, in the production of alcoholic beverages and as biological yeast for bread.

But the crucial point is that, like plants and animals, the S. cerevisiae It is a eukaryote – that is, its cells have a complex structure and a nucleus whose DNA is organized into several pairs of coiled structures, the chromosomes. It is the same system adopted by human genetic material. Learn how to build chromosomes from scratch using S. cerevisiae it could pave the way to do this with all other eukaryotes.

The description of the work with the yeast genome 2.0 so far has just been published in the specialized journal Cell. The study was coordinated by Patrick Yizhi Cai, from the University of Manchester (United Kingdom), and Jef Boeke, from NYU Langone Health, a medical research center linked to New York University.

“Our motivation is to understand the fundamental principles of genomes by creating a synthetic version of them”, summarized Cai in an official statement. “The team has rewrote the yeast operating system, allowing us to move away from the era of manipulating a handful of genes at a time and start thinking about designing and building entire genomes from scratch.”

For now, the process still has a very artisanal side. The 16 chromosomes that correspond to the complete set of synthetic DNA were assembled separately in different strains of yeast grown in the laboratory.

Then, scientists began to “concentrate” artificial chromosomes in the same cell through crossbreeding (since yeast reproduce sexually). It was enough to cross two strains that each carried a synthetic chromosome, so that at least part of their “offspring” carried both sets of DNA.

Through this process and another technique, which does not depend on crossing, the team reached a total of 7.5 synthetic chromosomes in the same yeast, which is equivalent to more than 50% of the species’ DNA (since some chromosomes are larger than However, as in the human genome, it was not necessary to exceed eight artificial chromosomes to reach this mark).

For one, the approach taken by researchers is creating a synthetic genome without some of the features that contribute to the unpredictability of natural DNA. They removed, for example, mobile elements – pieces of DNA that can jump from one part of the genome to another, copying themselves into new sections in a process that can modify other genes.

They also removed introns, which are stretches of DNA that undergo an editing process when they are transcribed into a sister molecule, RNA, and do not directly serve as a recipe for the production of proteins in the cell. They also inserted chemical “letters” of DNA that function as a kind of barcode for the synthetic genome and embedded a system that scrambles part of the yeast genome, with the aim of creating genetic variation that could be useful in the future.

But the potentially most radical change was the possibility that synthetic yeast DNA could serve as a recipe for the production of amino acids that are not used in nature to produce proteins, which could lead to creating cells with significantly different biochemistry than today.

“We decided it was important to produce something that was heavily modified from nature’s design,” explains Jef Boeke. “Our main goal was to build yeast that would be able to teach us new things about biology.”