Bridging the Genotype and the Phenotype: Towards An Epigenetic Landscape Approach to Evolutionary Systems Biology

Understanding the mapping of genotypes into phenotypes is a central challenge of current biological research. Such mapping, conceptually represents a developmental mechanism through which phenotypic variation can be generated. Given the nongenetic character of developmental dynamics, phenotypic variation to a great extent has been neglected in the study of evolution. What is the relevance of considering this generative process in the study of evolution? How can we study its evolutionary consequences? Despite an historical systematic bias towards linear causation schemes in biology; in the post-genomic era, a systems-view to biology based on nonlinear (network) thinking is increasingly being adopted. Within this view, evolutionary dynamics can be studied using simple dynamical models of gene regulatory networks (GRNs). Through the study of GRN dynamics, genotypes and phenotypes can be unambiguously defined. The orchestrating role of GRNs constitutes an operational {\em non-linear} genotype-phenotype map. Further extension of these GRN models in order to explore and characterize an associated Epigenetic Landscape enables the study of the evolutionary consequences of both genetic and non-genetic sources of phenotypic variation within the same coherent theoretical framework. The merging of conceptually clear theories, computational/mathematical tools, and molecular/genomic data into coherent frameworks could be the basis for a transformation of biological research from mainly a descriptive exercise into a truly mechanistic, explanatory endeavor.