Shapiro redux: humans edit yeast DNA (Introduction)

by David Turell , Friday, November 10, 2023, 15:33 (169 days ago) @ David Turell

And grow functional yeast:

https://www.sciencemagazinedigital.org/sciencemagazine/library/item/10_november_2023/41...

"A 17-year project to craft a synthetic genome for yeast cells has reached a watershed. Researchers revealed this week in 10 new papers that they have created designer versions of all yeast chromosomes and incorporated almost half of them into cells that can survive and reproduce. “It’s a milestone we have been working on for a long time,” says geneticist Jef Boeke of NYU Langone Health, director of the project.

"Researchers have tinkered with the genomes of yeast and many other organisms using editing technologies such as CRISPR. But building a new version from the ground up opens the way to making bigger changes to an organism’s genome and delving deeper into its organization, function, and evolution.

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"The researchers didn’t attempt to redesign the genome one nucleotide at a time. Instead, they revised the native yeast genome, adding thousands of modifications that simplify its structure, boost its stability, and make it easier to study. For instance, they carved out the transposons, itinerant stretches of DNA that can leap from location to location in the genome, disrupting DNA sequences.

"They also pruned the genome by excising many of the introns, segments of DNA that don’t code for portions of proteins. And to make the new yeast genome easier to manipulate in future experiments, the team included several hundred short DNA sequences that can prompt sections of chromosomes to rearrange.

"In most cases, the researchers left genes on their original chromosomes. But a team led by synthetic biologist Yizhi “Patrick” Cai of the University of Manchester, international director of the project, created a new, 17th chromosome to house yeast’s 275 tRNA genes. They code for RNA molecules that transport amino acids, the building blocks of proteins.

"Although tRNAs are essential for protein synthesis, their genes “are a lot of trouble for the genome,” Cai says, because “they are DNA damage hotspots” that can cause breaks. By isolating these disruptive genes on one chromosome, the researchers hoped to tame them. They found that yeast cells could survive and grow—albeit more slowly than unmodified cells—with this newfangled chromosome, they report in Cell. Synthetic biologist Paul Freemont of Imperial College London calls this work “a tour de force.”

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"Boeke and colleagues repeatedly mated cells harboring different synthetic chromosomes, eventually producing yeast that contained six full-size synthetic chromosomes and a fragment of another, but not the extra tRNA chromosome.

"This yeast grew slower than normal because of some harmful genomic glitches, but after the researchers identified and corrected them, the strain grew about as fast as unaltered cells, the team reported in a second Cell paper. They then used a similar mating approach to add another synthetic chromosome, bringing the total to 7.5. In these cells, more than 50% of the DNA is synthetic. “We are more than halfway there,” Boeke says.

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"The team is now working to integrate the remaining chromosomes into a yeast cell and correct any genomic problems that arise. Boeke expects a yeast with a fully synthetic genome to debut in about a year."

Comment: now we ae doing God's work, not speciating in a real sense. Remember we are using living material to do the editing, so our editing is secondhand. We do not know how genes really produce their results. We simply know what genes produce.