Response Doctoral Program

Plant breeding has been remarkably successful in developing high-yielding crop cultivars that have helped to sustain global food production over the last century. For instance, in the United States, the yield of the hybrid corn was increased 3 times, from 4 tons per hectare in the 1960s to 12 tons per hectare in 2017. By selecting and crossing plants with desirable traits, breeders have created crops that are more productive and adapted to intensive agriculture. However, this success has come with a trade-off: breeding has relied on genetic variation within a very limited primary gene pool, which has been shrinking due to genetic bottlenecks caused by domestication and intensive selection. As a result, today’s crops have lost much of their natural genetic diversity, making further improvement increasingly difficult.

To ensure future food security, we need to explore alternative sources of variation. One way to overcome the limited genetic diversity in modern crops might be to include epigenetic variation into breeding programs (Figure 1).

Could epigenetic variation be the right choice?

When considering the traits that define an organism, we typically think of DNA as the determining factor. More specifically, a certain stretch of the DNA, known as a gene, typically determines a specific trait. However, DNA alone does not determine the expression of a trait. Beyond genetics, epigenetic gene regulation adds another layer of control that determines whether a gene is active or inactive. Epigenetic regulation is mediated by naturally occurring chemical modifications of the DNA or of DNA associated proteins, neither of which alter the genetic code itself. These modifications act like molecular switches, regulating whether or not a certain gene is expressed in a given tissue or cell type of the plant. Thus, epigenetic modifications influence the expression of traits and may serve as an additional source of diversity, potentially compensating for the loss of genetic variation, thereby offering new opportunities for plant breeding.

Major challenge: Is DNA methylation reliably inherited? 

One of the chemical modifications is DNA methylation, involving the addition of a small methyl group to cytosine, one of the four bases that make up DNA. DNA methylation has been largely overlooked as a possible resource for crop improvement. This is mainly because it is considered less heritable than the DNA itself when passed on to subsequent generations. Regions of the genome that have different DNA methylation patterns between parental lines are known as epialleles. While genes follow predictable patterns of inheritance, the same does not always apply to the inheritance of epialleles. This especially refers to the inheritance of epialleles in hybrid plants created by crossing two distinct parental lines. In some cases, the methylation pattern of one inherited epiallele is altered to resemble that of the other, making their inheritance less predictable. Although initial reports claimed that such changes are very common, other studies on this topic reported inconsistent results. A proper understanding of the stability of epialleles across generations is thus crucial to evaluate a potential role for epigenetic marks like DNA methylation in future breeding programs.

Therefore, we tried to provide deeper insights into the stability of DNA methylation by addressing two questions: (1) How is DNA methylation inherited in crosses between two plants? And (2) Can DNA methylation be transmitted over many generations of inbreeding?Since we were addressing some of the fundamental aspects of DNA methylation, we decided to do our research in the model plant Arabidopsis thaliana. Using this plant simplifies the study of the inheritance of epialleles due to its small genome, short life cycle, and extensive datasets. At the beginning of our project, we identified more than 100 epialleles by analysing publicly available data from a large number of natural A.thaliana accessions. We focused on epialleles where DNA methylation was inversely related to gene expression, and in some cases associated with the expression of phenotypic traits (Figure 2). Based on differences in methylation levels between accessions, we selected 30 such epialleles and tracked their inheritance patterns in hybrids derived from 11 accession pairs. We then followed their inheritance over several generations of inbreeding, similar to a typical breeding program.

Key research findings and their societal relevance

To our surprise, we found no evidence of unstable inheritance among the 30 epialleles monitored in 240 hybrid plants. Each epiallele retained the exact methylation pattern of its parent, demonstrating reliable heritability. Furthermore, after multiple generations of inbreeding, we observed that epialleles were inherited according to classical Mendelian laws, just like genes. This finding challenges the common assumption that epialleles are inherently unstable and, instead, revealed a predictable, heritable pattern of epigenetic variation. This discovery might open new opportunities for plant breeding by establishing epigenetic variation as a reliable tool to enhance phenotypic diversity. By using stable epialleles, breeders could introduce novel traits without altering DNA sequences, offering new strategies for crop improvement. This has far-reaching implications not only for the seed and agricultural industries but also for policy discussions on the role of epigenetics in sustainable agriculture. Recognizing epialleles as a stable source of variation could inform regulatory frameworks and support the development of more resilient and productive crop varieties to meet future food security challenges.

Secondment and collaboration with MWSchmid GmbH

Throughout my project, I had the privilege of collaborating with an exceptional industry partner, Marc Schmid, the founder of MWSchmid GmbH, based in Glarus, Switzerland. Marc is a highly skilled independent research consultant whose expertise spans data analytics, bioinformatics, statistics, data visualization, and experimental design. His deep knowledge in research fields such as molecular biology, genetics, epigenetics, and ecology made him an ideal collaborator for my project. During my secondment, we worked closely together to analyze the initial data from my experiments, laying a strong foundation for the project. Even after the secondment concluded, our partnership continued, as we tackled the remaining data, ensuring a thorough and insightful analysis of my experimental results.

Dušan Denić is a PhD Researcher at the Department of Plant and Microbial Biology at the University of Zurich as well as a RESPONSE fellow in the PhD program Science and Policy.

References

Bevan, Michael W., Cristobal Uauy, Brande BH Wulff, Ji Zhou, Ksenia Krasileva, and Matthew D. Clark. “Genomic innovation for crop improvement.” Nature 543, no. 7645 (2017): 346-354. https://www.nature.com/articles/nature22011

Atwell, S., Huang, Y. S., Vilhjálmsson, B. J., Willems, G., Horton, M., Li, Y., Meng, D., Platt, A., Tarone, A. M., Hu, T. T., Jiang, R., Muliyati, N. W., Zhang, X., Amer, M. A., Baxter, I., Brachi, B., Chory, J., Dean, C., Debieu, M., … Nordborg, M. (2010). Genome-wide association study of 107 phenotypes in Arabidopsis thaliana inbred lines. Nature, 465(7298), 627–631. https://doi.org/10.1038/nature08800

Schmitz, R. J., Schultz, M. D., Urich, M. A., Nery, J. R., Pelizzola, M., Libiger, O., Alix, A., McCosh, R. B., Chen, H., Schork, N. J., & Ecker, J. R. (2013). Patterns of population epigenomic diversity. Nature, 495(7440), 193–198. https://doi.org/10.1038/nature11968

This article is authored by Dušan Denić.