In a dramatic restructuring, two teams have created versions with vastly reduced chromosome counts.
For millions of years, brewer’s yeast and its close relatives have packed their DNA into 16 distinct chromosomes. Now, two teams have used CRISPR gene-editing to stuff all of yeast’s genetic material — save a few non-essential pieces — into just one or two chromosomes. The feat represents the most dramatic restructuring yet of a complex genome and could help scientists understand why organisms split their DNA over many chromosomes. And, to the researchers’ surprise, the changes had little effect on most functions of the yeast (Saccharomyces cerevisiae). “That was the biggest shocker — that you can just get away with this and yeast seem to shrug its shoulders,” says Jef Boeke, a geneticist at New York University whose team jammed the yeast genome onto a pair of chromosomes1. A China-based group used a different technique to make yeast with one ‘super-chromosome’2. Both teams report their findings in Nature on 1 August, 2018.
Yeast belongs to the eukaryotes, the branch of life that includes humans, plants and animals and whose cells store genetic material in a membrane-bound nucleus. But the number of chromosomes that eukaryotes have varies wildly and seems to have no correlation with the amount of genetic information they possess. In humans, genetic material is spread over 46 chromosomes, whereas male jack jumper ants (Myrmecia pilosula) have just 1. Single-celled brewer’s yeast — whose genome, at 12 million DNA letters long, is hundreds of times shorter than that of humans — boasts 16 chromosomes. “We don’t know why they have such different numbers,” says Zhongjun Qin, a molecular biologist at the Chinese Academy of Sciences’ Shanghai Institute of Plant Physiology and Ecology, whose team created the lone-chromosome yeast strain. “I thought it was probably random.”
Qin and his colleagues reasoned that if an organism’s chromosome count were down to chance rather than an underlying rule of nature, there should be no reason that a yeast cell shouldn’t be viable with 1 chromosome instead of 16. Researchers in the past had fused two3 — even four4 — yeast chromosomes together, and another team split the 16 chromosomes into 33. All products had viable cells5. But no one had ever performed such extreme genetic surgery as Qin and his colleagues set out to do several years ago. Their initial attempts ended in failure — until they turned to the genome-editing tool CRISPR–Cas9, which is adept at excising specific DNA sequences. Qin and his colleagues used CRISPR to remove DNA at telomeres, the ends of chromosomes that protect them from degrading. They also snipped out centromeres, sequences in the middle that are important to DNA replication.
These changes paved the way for a fit of tidying that would make home-organization guru Marie Kondo proud. The researchers first fused two chromosomes, then joined this product to another one, and in successive rounds, to another and another — until they were left with a lone-chromosome yeast strain.