strain, Lang explains. However, in one case, the ancestor defeated an evolved strain. “It didn’t make any sense,” Lang says. “These things have evolved for a thousand generations. How is it worse than when it started?” Lang and his team discovered an intracellular “killer virus” within the yeast genome they were using. This virus produces a toxin that kills yeast without the virus. As a yeast population in the Lang Lab evolved, the frst step had the virus that produced the toxin. In the second generation, the genome evolved to be more ft, but the killer virus within its cell lost the ability to produce the toxin while maintaining immunity to it. In the third generation, the yeast genome was even more ft and divided evenmore quickly, but the virus lost immunity due to the absence of the toxin. “So we have the ancestor which is less ft but produces a toxin that kills things that don’t have the immunity component.We have a real ft fnal strain, but it is sensitive to this toxin,” says Lang. “And sowe endedupuncoveringmechanistically how you can get these nontransitive efects. “… Evolution is like that. If you can take organisms today and drop them of 200 million years ago, that doesn’t mean they’re going to out-compete everything because they’ve had another 200 million years of evolution. There are lots of these nontransitive interactions. So that was interesting because we could fnd that in the lab, and that’s something that you just couldn't possibly do in a natural population.” Experimental Evolution & Human Health Experimental evolution can be applied to human health as well, ofering potential for a better understanding of genetic disorders. “Humans and yeast are quite a bit diferent,” says Lang, “but, essentially, they have many of the same genes.” This similarity allows Lang to apply mutations associated with human disease to a yeast strain and observe the outcomes. In a recent study, Lang andhis colleagues identifed a geneticmutation involved in human congenital disorders of glycosylation (CDG), raremetabolic diseases that lead to a variety of symptoms. They made that samemutation inyeast and conducted evolution experiments, observing thatmutation slowed the yeast’s growth. “What my lab is good at is evolving yeast to overcome slow growth,” says Lang. “And so we did evolution experiments with yeast that contain rare human disease genes, and we identifed other genes and pathways where mutations can compensate for these defects.” Lang and former Lehigh doctoral student Ryan C. Vignogna ’22 Ph.D., now a postdoctoral associate at Cornell University, along with colleagues from the University of Campania “Luigi Vanvitelli,” the National Research Council of Italy, Greenwood Genetic Center and biotech Public Beneft Corporation Perlara posted this paper on the biology preprint server bioRxiv. The team is now scaling this work to conduct evolution experiments on another group of rare human diseases. “We actually were able to identify interactions with human disease genes that were previously unknown. And normally, when people look for interactions with diferent genes, they delete one and they delete another “We actually were able to and they look to see if identify interactions with the deletions interact. But a lot of these human human disease genes that diseases are in genes that were previously unknown.” are essential, and so you can’t actually delete them. —Gregory Lang And so we were able to get a nice newwindowonwhat interactions human disease genes might have.” As his lab works at the forefront of experimental evolution, Lang continues to be intrigued by the unknown. How do changes in the genome result in changes in an individual? Can scientists more accurately predict evolution? A deeper understanding of these “inextricably linked” questions could help address a number of problems related to human health. “Random mutations happen, they change the phenotype, and that's what selection acts on,” he says. “[Evolution] is the most fundamental biological process, yet it’s one that we don’t understand well at all.” L 3 8 | L E H I G H B U L L E T I N 3 8 | L E H I G H B U L L E T I N
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