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Two Research Teams Engineer Yeast With Fewer Chromosomes Than Typical

NEW YORK (GenomeWeb) – Two independent research teams have stitched together baker's yeast chromosomes to determine the smallest number of chromosomes the fungus needs to survive. One group was able to combine the 16 usual yeast chromosomes into just one, while the other created a strain with just two chromosomes.

While Saccharomyces cerevisiae, also known as baker's yeast or budding yeast, has 16 chromosomes, its relative Schizosaccharomyces pombe, or fission yeast, has three chromosomes, despite a slightly larger genome size. This led the researchers to wonder what the advantages of having a certain chromosome count are.

The two teams, one from the Chinese Academy of Sciences and the other from NYU Langone Health, used genome editing tools to fuse baker's yeast chromosomes, while also removing the excess telomeric and centromeric regions. As the teams separately reported today in Nature, they both found that having fewer chromosomes altered the expression of only a few genes and led to few growth defects. However, they reported reduced fitness with decreasing chromosome number.

The NYU team, led by Jef Boeke, a researcher at the Institute for Systems Genetics, developed yeast with successively fewer chromosomes, first fusing the smaller yeast chromosomes to yield a strain with 12 chromosomes and then linking the others together to eventually yield a yeast strain with two chromosomes, each about 6 megabases in length. They noted in their paper that they attempted, but were unable, to generate a strain with a single chromosome.

The researchers led by the Chinese Academy of Sciences' Zhongjun Qin, however, were able to achieve this feat, as they reported in their paper. Through their series of chromosomal fusions, chosen randomly, they developed a yeast strain with just a single chromosome.

Why only one team was able to whittle the yeast chromosome number down to one is not clear, noted Gianni Liti from the University of Côte d'Azur in a related commentary in Nature, especially as they used similar approaches. He theorized that it could be due to differences in the order and orientation of the fusions or to the development of mutations affecting yeast tolerance to changes in genome organization.

Both the NYU and CAS teams noted that yeast strains with the smaller-than-usual number of chromosomes still harbored the typical complement of genes and, through transcriptomic analyses, found only a few differences in gene expression.

Many of the differentially expressed genes used to be, or still were, located near telomeres. Eight of the 28 genes Qin and his colleagues found to differ in expression are involved in stress response, suggesting that a giant chromosome might be burdensome.

Qin and his colleagues also noted changes in genome organization through a chromosome conformation capture-derived Hi-C assay. Overall, they found the genomic structure of the cells with one or two chromosomes to be twisted and globular. The remaining centromeres and telomeres tended to stay on the periphery and the chromosome arms were much more bent than usual.

When the research teams grew their minimal chromosome yeast strains in culture, they found little differences in cell growth. Boeke and his colleagues reported that their two-chromosome strain grew at about 91 percent of the rate of the wild type, suggesting that these strains are healthy.

The researchers did notice, though, a toll on sexual reproduction and fitness. Both found decreased spore viability with increasing chromosome fusions, and when Qin and his colleague conducted a competition between their single-chromosome strain and wild-type yeast, the wild-type strain dominated as co-culture time went on.

Boeke and his colleagues also crossed strains with varying chromosome complements to gauge when changes in chromosome number might lead to reproductive isolation. Eight fusion events, they reported, were enough to separate strains reproductively.

"Beyond the current findings, these engineered yeast strains constitute powerful resources for studying fundamental concepts in chromosome biology, including replication, recombination, and segregation," Liti added.