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).

TitleCortical 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).
Publication TypeJournal Article
Year of Publication2015
AuthorsAtkinson, EG, Rogers, J, Mahaney, MC, Cox, LA, Cheverud, JM
JournalGenetics
Volume200
Issue2
Pagination651-65
Date Published2015 Jun
ISSN1943-2631
KeywordsAnimals, Biological Evolution, Brain, Cerebral Cortex, Chromosome Mapping, Cluster Analysis, Papio, Pedigree, Primates, Quantitative Trait Loci, Reproducibility of Results
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.

DOI10.1534/genetics.114.173443
Alternate JournalGenetics
PubMed ID25873632
PubMed Central IDPMC4492386
Grant ListK12 GM102778 / GM / NIGMS NIH HHS / United States
P51 OD011133 / OD / NIH HHS / United States
P51 RR013986 / RR / NCRR NIH HHS / United States