Meeting Abstract
99.2 Thursday, Jan. 7 Investigating conservation and differentiation in related developmental gene regulatory networks GREENFEST-ALLEN, E*; KINGSLEY, P; PALIS, J; STOECKERT, CJ; Univ. of Pennsylvania, Philadelphia; Univ. of Rochester, Rochester; Univ. of Rochester, Rochester; Univ. of Pennsylvania, Philadelphia allenem@pcbi.upenn.edu
A central question in the study of biodiversity is how to resolve conservation of phylum-level traits with the changes that occur within phyla and the continuous modification of characters that leads to speciation. One explanation is that constraints progressively limit developmental flexibility, reducing evolvability through increasing integration of developmental pathways to the point that any deviation is catastrophic. Yet, increasing integration can also augment evolvability by improving redundancy and robustness. These opposing effects imply a hierarchical regulation of developmental whereby a conserved integrated framework regulates and links sets of tightly integrated interactions that act as a coherent unit (modules). Here we evaluate this hypothesis within a small-scale model system: the development of red blood cells (RBCs). In mammals, there are two types of RBCs: primitive and definitive, produced through three developmental lineages. In each, progenitors progress through comparable developmental stages and produce functionally equivalent, but phenotypically distinct RBCs. Accordingly, we expect the lineage-specific regulatory networks contain shared and unique sets of interactions. We integrate multiple data sources (e.g., co-expression, binding, pathways) to infer and weight interactions and estimate the regulatory network for each lineage. Modules and key genes are identified through computational analysis of the individual network topologies and are then compared to identify conserved and unique sets of interactions. We then assess the distribution of these interaction sets within the network graph to evaluate whether the structure affects the likelihood of conservation.
