The Genetic Architecture and Evolution of Brain Cortical Folding in a Pedigreed Primate Population
Date of Award
Doctor of Philosophy (PhD)
Elevated neurological faculty, related to the dramatic increase in brain volume, is a hallmark of the primates. Cognitive capacity, the processing power and speed of the brain, is directly related to the number of neurons in the cerebral cortex and the connectivity network underlying information processing in the brain. Increased cortical folding (gyrification) allows for more neurons to be contained within the volume of the braincase and the arrangement of folds and ridges across the cerebral cortex is an indication of the underlying neural network connecting regions. The goal of this dissertation is to develop a better understanding of the genetic processes that influence the evolution and development of sulci and gyri in primates. Characterizing gyrification's genetic basis allows examination of the source of the evolutionary changes in primate brain structure and, ultimately, function, a significant and relatively unexplored facet of evolutionary biology, anthropology, genetics, and neuroscience.
This sample population of nearly 1,000 pedigreed baboons gives very high statistical power, allowing me to confidently conclude that there is significant contribution of genes to variation in brain features. Using Mantel testing and two clustering methods (k-means and agglomerative hierarchical clustering), I find similar modularity motifs between phenotype and genotype, and within three theoretical matrices spanning other biological domains (development, anatomical brain lobe location, and connectivity). These results independently validate the genetic control over brain traits, provide indirect support for the Van Essen model of sulcal development, and indicate the high degree of morphological integration between phenotypic and genotypic variation. The partitioning of variation directly influences the ease of future evolutionary change and this well-integrated arrangement would allow for rapid and effectual selective cortical alteration.
In examining the directional asymmetry of the two brain hemispheres, I found that the endocasts are systematically asymmetric and that there is a genetic component to this asymmetry; baboons are genetically predisposed to be asymmetrical. Tests of fluctuating asymmetry showed that traits are differentially susceptible to developmental noise, with ones appearing earlier in ontogeny being more canalized and ones appearing on later embryonic days having much more variable phenotypes. Looking at cross-hemisphere trait correlations, I deduce that developmental pathways for sulci do not span the midline of the brain, but instead are restricted within each of the two hemispheres. I additionally find neuroanatomical suggestions of handedness in the baboon from examining population-wide trends in frontal petalia direction, corroborating prior behavioral evidence.
QTL statistical genetic mapping analyses were conducted to connect phenotypic variation to specific portions of the baboon genome, pinpointing a handful of chromosome segments that affect gyrification. The best of these QTL peaks contain compelling candidate genes that have already been implicated in influencing brain development and function. The distribution of peaks elucidates a complex pattern of genetic control over brain traits, with indications of both pleiotropy and polygeny. Fine-mapping is currently underway, which will allow me to validate positional candidate genes and independently associate specific SNPs with variation in brain features.
All in all, this project hopes to answer fundamental questions about the genetic architecture of brain cortical gyrification, a trait that has important implications for the evolution of neural networks in both human and non-human primates. This dissertation provides a framework of the genetic basis of primate brain folding and investigates the evolutionary and developmental mechanisms responsible for its formation. Gyrification is an overlooked aspect of brain evolution and characterizing it genetically elucidates the biological underpinnings contributing to structural differences in the cerebral cortex between primates.
Chair and Committee
James M Cheverud
Alan Templeton, Bruce Carlson, Glenn Conroy, Jeffrey Rogers, David Van Essen
Atkinson, Elizabeth Grace, "The Genetic Architecture and Evolution of Brain Cortical Folding in a Pedigreed Primate Population" (2013). Arts & Sciences Electronic Theses and Dissertations. 49.
Permanent URL: https://doi.org/10.7936/K7DZ0677