THE ROLE OF DEVELOPMENTAL BIAS IN A SIMULATED EVO-DEVO SYSTEM by SEAN THOMAS PSUJEK Submitted in partial fulfillments of the requirements For the degree of Doctor of Philosophy Department of Biology CASE WESTERN RESERVE UNIVERSITY May, 2009 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of _____________________________________________________ candidate for the ______________________degree *. (signed)_______________________________________________ (chair of the committee) ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ (date) _______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. Table of Contents Abstract .............................................................................................................................. 2 List of Figures ................................................................................................................... 4 Chapter 1 : Introduction ...................................................................................................... 6 Chapter 2 : Background .................................................................................................... 12 Modeling in Evo-devo ................................................................................................ 12 Influence of evolution on gene regulation .............................................................. 14 Chapter 3 : The Developmental Model ....................................................................... 15 Introduction ................................................................................................................ 15 The developmental model ......................................................................................... 16 An example demonstrating development of a neural circuit ............................... 22 Chapter 4 : Characterizing Developmental Bias ........................................................ 25 Introduction ................................................................................................................ 25 Visualization of bias in this system .......................................................................... 26 An intrinsic bias exists in the developmental system ........................................... 26 Developmental bias varies with genotype .............................................................. 30 Degenerate genotypes have different patterns of bias .......................................... 33 Genotypes along a neutral network differ in their pattern of bias ...................... 34 Regulatory structure shapes developmental bias .................................................. 36 Chapter 5 : Characterizing the Interaction between Developmental Bias and Selection .......................................................................................................................... 42 Introduction ................................................................................................................ 42 The evolutionary simulation ..................................................................................... 42 Visualization of fitness and local bias ..................................................................... 44 Conceptual Framework ............................................................................................. 45 Results ......................................................................................................................... 50 Lineage analysis .......................................................................................................... 52 Population analysis .................................................................................................... 64 Initial epoch ............................................................................................................ 67 Final epoch .............................................................................................................. 68 Intermediate epochs .............................................................................................. 70 Chapter 6 : Discussion ................................................................................................... 73 Characterizing Developmental Bias ........................................................................ 75 Characterizing the Interaction between Developmental Bias and Selection ..... 78 Future Work ................................................................................................................ 81 Conclusions ................................................................................................................. 83 Chapter 7 : References ................................................................................................... 83 1 The Role of Developmental Bias in a Simulated Evo-Devo System Abstract by SEAN THOMAS PSUJEK The success of the Modern Synthesis has resulted in forces of evolutionary change other than natural selection being marginalized. However, recent work has attempted to show the importance of non-selective influences in shaping organic form. One such force is developmental bias, the differential produced of phenotypes. I use a simulation model of neural development to explore questions of general interest about developmental systems. From an analysis of the bias in the production of phenotypic variants in the developmental model, I find the pattern of developmental bias varies strongly with the genotype even among phenotypically-neutral genotypes. In addition to this genotype- dependent developmental bias (local bias), an intrinsic bias exists in the developmental system (global bias). I also show that developmental bias varies among related genotypes that produce the same phenotype. Finally, I illustrate how a pattern of bias emerges from the manner in which mutations affect the regulatory structure of the wild- type genotype. These results suggest that developmental bias could have a strong influence on the direction of evolutionary modification. In subsequent analyses exploring the interaction of developmental bias and selection during adaptive evolution, I find developmental bias guides phenotypic transitions with the result that multiple 2 phenotypic pathways are taken towards the target phenotype across simulations. I also find higher-fitness phenotypes often become accessible with the accumulation of selectively-neutral mutations. The change in accessibility is due to alterations of the regulatory structure of the genotypes through the neutral mutations. This lability of developmental bias recommends a comparative approach to the experimental investigation of bias in natural systems. The alteration of phenotypic accessibility following the accumulation of neutral mutations can be conceptualized as a population moving along a network of isofitness genotypes linked by mutations (neutral networks). The phenotypes produced by non-fitness-neutral neighbors of the neutral genotypes are likely to vary as the population moves to different regions of the network. These networks are created by the mutational operator and the degeneracies of the dual mappings of genotype to phenotype and phenotype to fitness. Topological properties of the neutral networks could lead to insights into the impact on evolvability of developmental systems. 3 List of Figures Figure 1-1: A radially-represented uniform distribution of genotypes leading to a non-uniform distribution of phenotypes through a developmental process. ..................................................................................................... 7 Figure 3-1: Model gene and sequences corresponding to protein types. ........................................................... 18 Figure 3-2: The three stages of development in the formation of a three-neuron circuit with three synaptic connections. ........................................................................................................................................................... 21 Figure 3-3: Genome that produces the three-connection circuit in Figure 3-2, stage 3. .................................. 22 Figure 3-4: The differentiation steps as generated by the genome in Figure 3-3.............................................. 24 Figure 4-1: Developmental bias exists in the model system. .............................................................................. 28 Figure 4-2: Ten most commonly produced neural circuits through random sampling of genotypes and the number of sampled genotypes that result in the given circuit. .......................................................................... 30 Figure 4-3: Local bias patterns for four specific genotypes. ............................................................................... 31 Figure 4-4: Local bias patterns for eight genotypes that produce the same neural circuit from our random sample. .................................................................................................................................................................. 33 Figure 4-5: Local bias patterns along a neutral network. ................................................................................... 35 Figure 4-6: New phenotypes