Cortical Folding of the Primate Brain: An Interdisciplinary Examination of the Genetic Architecture, Modularity, and Evolvability of a Significant Neurological Trait in Pedigreed Baboons (GenusPapio)

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.KEYWORDS gyrification; QTL; cerebral cortex; heritability; primate brain; evolution; modularity; Papio hamadryas T HE extent of folding of the cerebral cortex, known as "cortical gyrification," has dramatically increased during primate evolution, in parallel with increasing brain volumes. The cortex of Old World monkeys is significantly more folded (gyrified) than that of New World monkeys (Zilles et al. 1989;Martin 1990), and the great apes have the highest degree of gyrification in nonhuman primates (Preuss et al. 2004). Humans are outliers even within the primate clade, with our brain being almost 30% more folded than that of chimps (Rogers et al. 2010). Powerful physical constraints on the upper limit of human neonatal brain volume drive selection toward the most compact brain possible (Rosenberg and Trevathan 2002), while humankind's ecological niche demands high cognitive potential. Since the cell bodies of neurons-the functional units of information processing in the brain-are located in the outermost layer of the laminar brain system, folding the cerebral cortex is an effective method of increasing surface area in which to allocate neurons with minimal overall brain volume expansion. Selection for a larger brain volume does not autom...

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