Dissecting the forces that govern epigenetic memory

Organisms transmit more than just genetic information across generations: they may also pass on a “memory” of the factors that affected how their ancestors’ genes functioned. These factors, called epigenetic processes, or “beyond genetics”, are common in plants. One such epigenetic process is called gene-body methylation (gbM). GbM refers to the chemical modification of a specific sequence motif in genetic coding regions and predominantly affects genes that are required for the maintenance of basic cellular functions. Geographically distinct natural populations of the model plant Arabidopsis thaliana demonstrate striking differences in their gbM patterns. In their latest paper in PLoS Genetics, researchers from the Nordborg group at GMI investigate the factors underlying the epigenetic memory of gbM in Arabidopsis. By crossing individuals from two natural variants with distinct gbM patterns (high gbM vs. low gbM) and using population genetics, the scientists demonstrate that a strong interaction between the plants’ inherited genetic makeup and environmental factors determines the conservation and transmission of the gbM pattern to the offspring.

To peek into the mechanisms of cross-generational transmission patterns of gbM, first author and recent GMI PhD graduate Rahul Pisupati and the team investigated the possibility of gbM patterns being influenced by genetic factors, the environment, or a combination of the two. The researchers crossed Arabidopsis individuals from a southern Swedish population that is known to have low gbM with individuals from a northern Swedish population that has high gbM. They then performed population genetics analyses. By sequencing the methylation patterns of large sample sizes of several hundred individuals across two offspring generations, the researchers showed that the transmission of methylation patterns largely followed Mendelian laws. However, deviations (i.e., gains or losses of methylation at a given site) predominantly affected sites where the methylation patterns already differed between the parental lines. The team demonstrated that the gains and losses of methylation were largely influenced by the state of methylation of the surrounding genetic environment and that these deviations showed a strong gene-environment interaction.

With this study, the researchers of the Nordborg group demonstrated that genetics alone could not explain the inheritance of the gbM patterns, but rather that an interplay of the genetic makeup with environmental factors (“gene-environment interaction” or G×E) is an essential factor. They hypothesize that these driving forces are included in the zygote to ensure their transmission to the offspring. These findings shed light on how the northern and southern Swedish Arabidopsis populations came to develop their distinct gbM patterns.