Compacting The Yeast Genome Into A Single Chromosome

Using the CRISPR/Cas9 gene editing system, scientists in China have created single-chromosome yeast to study the evolutionary benefits or drawbacks of having multiple chromosomes.

AsianScientist (Aug. 24, 2018) – Researchers at the Chinese Academy of Sciences (CAS) have compacted the genome of yeast (Saccharomyces cerevisiae) into a single chromosome. Their findings were published in Nature.

In eukaryotes, genetic material is compacted into structures called chromosomes. Nearly all known eukaryotes have multiple chromosomes, though the size and number of chromosomes can vary across species. Humans, for instance, possess 23 pairs of chromosomes, while S. cerevisiae have 16 pairs.

Why most eukaryotes evolved multiple chromosomes is unknown. To shed light on the evolutionary benefits and drawbacks of having multiple chromosomes, a team of scientists at the CAS Center for Excellence in Molecular Plant Sciences in China combined all 16 chromosomes of S. cerevisiae into a single, giant chromosome and observed whether this artificial strain could survive and mate.

The researchers accomplished this ‘Frankenstein’ feat using the CRISPR/Cas9 gene editing tool, relying on homologous recombination, a DNA repair mechanism intrinsic to cells, to achieve successive end-to-end chromosome fusions. They managed to produce an 11.8-Mb-long, linear artificial chromosome with two arms of roughly equivalent length on each side of a single linking structure known as a centromere. The artificial yeast remained viable after the procedure, although the researchers noted unusual three-dimensional structures in the colossal chromosome.

Going further, the researchers examined and compared various biological profiles of the artificial yeast strain to those of natural yeast. They found that the pattern of global gene expression was nearly identical in both the artificial and natural strains. However, several genes related to the stress response were upregulated, likely a result of topological stress induced by the chromosome’s length, said the researchers.

Both strains also exhibited similar phenotypic profiles, that is, their characteristics and morphology were largely the same. These results suggested that combining all 16 chromosomes into a single large chromosome had little effect on gene transcription.

While these findings indicate that having multiple chromosomes is optional to sustaining life (at least in yeast), they also imply that organizing the genetic material into a single chromosome may not be functionally optimal. The researchers also found that chromosomal replication and segregation, key processes in cell division were impaired in the artificial yeast strain. Because of this, the artificial strain reproduced at a slower rate and was outcompeted by wild-type yeast.

The researchers highlighted that their synthetic biology approach to creating organisms with single chromosomes could help advance the fields of telomere biology and meiotic recombination.

The article can be found at: Shao et al. (2018) Creating a Functional Single-chromosome Yeast.


Source: Chinese Academy of Sciences; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Lim Zeng Hao completed a degree in biological sciences at Nanyang Technological University, Singapore. In his spare time, he dabbles in new languages and daydreams about the eventual publication of his epic fantasy book series. Zeng Hao is a science writer with Asian Scientist Magazine.

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