Scientists believe that humans once boasted 24 pairs of chromosomes, just like other primates, until at some point in our distant past, 2 pairs fused into one, leaving us with 23 pairs. That transformation inspired Jef D. Boeke, PhD, director of the Institute for Systems Genetics at NYU Langone Health, to wonder how well other species might tolerate such big genetic changes.
In the case of brewer’s yeast, the answer is... quite well. In a new study published in the journal Nature, Dr. Boeke and colleagues found that the single-celled organism used to make beer and bread thrives even after its normal set of 16 chromosomes have been fused together to form 2 megachromosomes.
“What we asked, broadly, is how extensively we could rewrite a genome and still have a healthy organism come out at the other end,” says Dr. Boeke, a leader in the emerging field of synthetic biology. “What we found is that yeast is amazingly adaptable.”
This genomic flexibility may lead to a better understanding of how human cells divide and provide instructions to their progeny, given that yeast possess a cellular organization similar to ours. Such knowledge, says Dr. Boeke, could aid researchers in determining how extra or missing chromosomes are passed on—sometimes resulting in miscarriages or genetic disorders such as Down syndrome—and may lay the groundwork for therapeutic interventions to prevent or repair such chromosomal anomalies.
Dr. Boeke and his colleagues harnessed bacteria to fuse the ends of each yeast chromosome together. The reengineered cells reproduced successfully, though they could no longer do so with their unaltered counterparts. In engineered strains, Dr. Boeke’s team found that healthy progeny depended upon a certain numeric compatibility among their parents: When males and females possessed the same number of chromosomes—be it eight, four, or two—their mating was successful. If their chromosomes mismatched, say, with 16 chromosomes in a male and only 8 in a female, reproduction failed.
Beyond medicine, these findings could help control the harmful spread of genetically modified species in the wild. The process studied mimics a key step in evolution, in which isolated populations can evolve into a new species over time. In this case, the researchers found that as few as eight fusions were enough to completely isolate the two yeast populations from each other, in effect creating a separate species virtually overnight. “Our work sheds light on the wild trajectory of accidental chromosome duplications and fusions across evolution,” says Dr. Boeke. “We are learning how one species becomes two.”