The role of DNA methylation in generating quantitative traits and inter-individual variations

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Background: A continuous distribution of inter-individual phenotypic variation amongst members of a population is a pervasive feature of all living organisms. While classical genetics can easily explain binary traits caused by Mendelian inheritance of rare alleles, the continuous distribution of quantitative traits is more difficult to explain. It is also well established that the environment could play a role in altering quantitative traits, however the mechanisms responsible are unclear. Understanding the fundamental mechanisms responsible for generating quantitative traits in biological systems have foundational theoretical implications for biology as well as practical implications. DNA methylation is a covalent modification of DNA that silences gene expression without alteration of the gene sequence and in contrast to germ line mutations that are identical across all cells and tissues, the state of methylation of a gene could vary from cell to cell even in the same tissue increasing the potential for a continuous variation. Thus, DNA methylation is well positioned to create a distribution of quantitative traits. Together with my collaborator Ehab Abouheif we addressed this question using ant societies and provided a proof of principle that DNA methylation can generate quantitative variation in a complex trait by quantitatively regulating transcription of the Epidermal growth receptor (Alvarado et al., Nature Com). Ants offer a unique opportunity to approach this foundational biological question since these are natural animals and not inbred lab rodents, we can study large numbers of individuals, easily manipulate the environment and their genomes are compact allowing high throughput deep sequencing.***Specific aims: Our study will examine first, whether there is natural interindividual variation in DNA methylation in Camponotus floridanus ants at many loci across the genome, second, whether this is responsible for continuous inter-individual distribution of a battery of quantitative traits, third whether these variations in DNA methylation are environmentally driven and fourth whether these distribution of traits could be shifted by environmental manipulations using genome-wide bisulfite sequencing behavioral and morphometric phenotyping and environmental and genetic manipulations to test causation. ***Significance: This study will test one of the most foundational hypothesis in biology, that there is a dialogue between environments and genomes and that the phenotypic outcome of this dialogue is the natural inter-individual phenotypic variation that creates the heterogeneity of living populations. Since epigenetics is reversible, an epigenetic basis for natural phenotypic variation would pave a path for targeted interventions that will have an impact on biotechnology fishery, farm animals and agriculture. **