CRISPR Creates New Single-Chromosome Species of Yeast
Researchers at the Key Laboratory of Synthetic Biology in Shanghai have used CRISPR to create a new species of yeast that only has a single giant chromosome. The work, which was published in Nature yesterday, demonstrates the tremendous power of CRISPR as a gene editing tool, as well as providing researchers with new insights into the nature of chromosomes. The study was completed in parallel to another independent paper published in the same journal, which used CRISPR to reduce the number of chromosomes in a yeast cell to 2.
In nature, Saccharomyces cerevisiae (a species of budding yeast) possess 16 distinct chromosomes that vary between 230 to 1,532 kilobases in length. These chromosomes are structurally very similar to that of human cells – with telomere caps at either end to protect the DNA and a centromere in the middle that enables accurate separation of paired chromosomes during cell division. Despite the universal presence of chromosomes in natural cells, however, researchers are not quite sure why the structures are necessary.
To learn more, a team of researchers in Shanghai, led by Dr Zhongjun Qin, wanted to reduce the number of chromosomes down to just one. This was not as simple as stitching the chromosomes together, however; in order for the superstructure to retain the properties of a chromosome, it had to maintain a single centromere with telomere caps.
To do so, the two teams used the gene editing tool CRISPR to remove the telomere caps at one end of two separate chromosomes, while simultaneously removing one of the two centromeres present. The fragments could then be fused together to form a single chromosome with one centromere and telomere sequences only present at the ends of the molecule. By repeating this approach across many different chromosomes, the teams were able to generate viable, living yeast cells with one or two chromosomes.
Both groups then investigated how their activity had influenced the biology of the cells. They noted that certain traits, including cell growth, size, and shape, were buffered throughout the manipulation process, and that gene expression only altered significantly for a very small number of sequences. In many cases, these changes in gene expression were accounted for by the removal of nearby telomere sequences, which minimise transcription.
The researchers also found that the manipulated yeast was not able to reproduce well with 16-chromosome yeast, but was fertile amongst other single-chromosome cells. This indicates that the modified cells may not only be a new form of yeast, but could constitute a whole new, man-made species altogether.
“In this study, we created a biologically functional S. cerevisiae (SY14) with a single giant chromosome by successive fusion of sixteen native chromosomes, representing, to our knowledge, the first example of a eukaryote with a single linear chromosome created in the laboratory,” the authors of the first paper wrote.