title: Cortical Folding of the Primate Brain: An Interdisciplinary Examination of the Genetic Architecture, Modularity, and Evolvability of a Significant Neurological Trait in Pedigreed Baboons (Genus Papio).
abstract: Folding of the primate brain cortex allows for improved neural processing power by increasing cortical surface area for the allocation of neurons. The arrangement of folds (sulci) and ridges (gyri) across the cerebral cortex is thought to reflect the underlying neural network. Gyrification, an adaptive trait with a unique evolutionary history, is affected by genetic factors different from those affecting brain volume. Using a large pedigreed population of ∼1000 Papio baboons, we address critical questions about the genetic architecture of primate brain folding, the interplay between genetics, brain anatomy, development, patterns of cortical-cortical connectivity, and gyrification's potential for future evolution. Through Mantel testing and cluster analyses, we find that the baboon cortex is quite evolvable, with high integration between the genotype and phenotype. We further find significantly similar partitioning of variation between cortical development, anatomy, and connectivity, supporting the predictions of tension-based models for sulcal development. We identify a significant, moderate degree of genetic control over variation in sulcal length, with gyrus-shape features being more susceptible to environmental effects. Finally, through QTL mapping, we identify novel chromosomal regions affecting variation in brain folding. The most significant QTL contain compelling candidate genes, including gene clusters associated with Williams and Down syndromes. The QTL distribution suggests a complex genetic architecture for gyrification with both polygeny and pleiotropy. Our results provide a solid preliminary characterization of the genetic basis of primate brain folding, a unique and biomedically relevant phenotype with significant implications in primate brain evolution.
authors: Department of Anatomy and Neurobiology, Washington University in St. Louis School of Medicine, St. Louis, Missouri 63110 elizabeth.atkinson@stonybrook.edu.
authors: Elizabeth G
authors: EG
authors: Atkinson
authors: Human Genome Sequencing Center and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030.
authors: Jeffrey
authors: J
authors: Rogers
authors: South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio and Regional Academic Health Center, Harlingen, Texas 78550 Department of Genetics and Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas 78245.
authors: Michael C
authors: MC
authors: Mahaney
authors: Department of Genetics and Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas 78245.
authors: Laura A
authors: LA
authors: Cox
authors: Department of Anatomy and Neurobiology, Washington University in St. Louis School of Medicine, St. Louis, Missouri 63110 Department of Biology, Loyola University, Chicago, Illinois 60660.
authors: James M
authors: JM
authors: Cheverud
mesh_terms: D000818:Animals; D005075:Biological Evolution; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology*; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000502:physiology*; D002874:Chromosome Mapping; D016000:Cluster Analysis; D010215:Papio; D010375:Pedigree; D011323:Primates / Q000235:genetics*; D040641:Quantitative Trait Loci; D015203:Reproducibility of Results
keywords: Papio hamadryas; QTL; cerebral cortex; evolution; gyrification; heritability; modularity; primate brain