Yeast study provides insight into longstanding evolutionary debate

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Over the past two decades, researchers have shown that the biological traits of species and individual cells can be shaped by the environment and inherited even without genetic mutations, a finding that contradicts one of the classic interpretations of Darwinian theory.

But exactly how these epigenetic, or non-genetic, traits are inherited is unclear.

Now, in a study published Oct. 27 in the journal Cell Reports, Yale scientists show how epigenetic mechanisms contribute in real time to the evolution of a gene network in yeast. Specifically, across multiple generations, yeast cells have been shown to transmit the changes in gene activity induced by the researchers.

The finding helps shed light on a long-standing question in evolutionary biology; scientists have long wondered if organisms can pass on traits acquired over a lifetime.

Should genetic mutations be the sole facilitator of gene network evolution or can epigenetic mechanisms also lead to stable and heritable gene expression states maintained generation after generation? asked Yale’s Murat Acar, associate professor of molecular, cellular, and developmental biology, Yale Systems Biology Institute faculty member, and senior author of the paper.

For much of the last half of the 20th century, students of biology learned that mutations in genes that helped species adapt to the environment were passed down from generation to generation, ultimately resulting in tremendous diversity in the life. However, this theory had a problem: advantageous mutations are rare, and it would take several generations for the physiological changes caused by the mutation to take hold in a population of a given species.

Scientists of the last century discovered that certain regions of DNA do not code for genes but regulate gene activity in the face of environmental changes. The concept of transmitting stable gene expression states to offspring resurrected the once largely discredited theories of 18th-century French scientist Jean-Baptiste Lamarck, who first proposed the inheritance of traits acquired during a life.

For the new study, graduate students from the Acar lab and co-first authors Xinyue Luo and Ruijie Song wanted to investigate the role of epigenetic inheritance in the evolution of gene network activity in individual yeast cells. , which reproduce asexually approximately every 100 minutes. As an experimental model, they studied a network of genes known as the galactose utilization network, which regulates the utilization of galactose, a sugar-like molecule, in yeast. Using daily cell sorting, they separated the cells that had the lowest levels of gene expression in the population and grew those cells in the same environment over a period of seven days.

Ultimately, they found that reductions in expression level persisted for several days and generations of reproduction after the 7-day segregation period. Genetic causes alone could not explain the reduced expression; inheritance of epigenetic factors contributed to the observed change, the Yale team found.

Acar said the results show a clear Lamarckian epigenetic contribution to the evolution of the gene network and that the classic Darwinian interpretation of evolution alone cannot explain our observations. “The results support the idea that genetic and epigenetic mechanisms must be combined in a ‘grand unified theory of evolution,'” he said.

Other authors include Mark Hochstrasser, Eugene Higgins Professor of Molecular Biophysics and Biochemistry and Professor of Molecular, Cellular and Developmental Biology, and postdoctoral associates David Moreno and Hong-Yeoul Ryu.

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