Elsevier

NeuroImage

Volume 53, Issue 3, 15 November 2010, Pages 1103-1108
NeuroImage

On the genetic architecture of cortical folding and brain volume in primates

https://doi.org/10.1016/j.neuroimage.2010.02.020Get rights and content

Abstract

Understanding the evolutionary forces that produced the human brain is a central problem in neuroscience and human biology. Comparisons across primate species show that both brain volume and gyrification (the degree of folding in the cerebral cortex) have progressively increased during primate evolution and there is a strong positive correlation between these two traits across primate species. The human brain is exceptional among primates in both total volume and gyrification, and therefore understanding the genetic mechanisms influencing variation in these traits will improve our understanding of a landmark feature of our species. Here we show that individual variation in gyrification is significantly heritable in both humans and an Old World monkey (baboons, Papio hamadryas). Furthermore, contrary to expectations based on the positive phenotypic correlation across species, the genetic correlation between cerebral volume and gyrification within both humans and baboons is estimated as negative. These results suggest that the positive relationship between cerebral volume and cortical folding across species cannot be explained by one set of selective pressures or genetic changes. Our data suggest that one set of selective pressures favored the progressive increase in brain volume documented in the primate fossil record, and that a second independent selective process, possibly related to parturition and neonatal brain size, may have favored brains with progressively greater cortical folding. Without a second separate selective pressure, natural selection favoring increased brain volume would be expected to produce less folded, more lissencephalic brains. These results provide initial evidence for the heritability of gyrification, and possibly a new perspective on the evolutionary mechanisms underlying long-term changes in the nonhuman primate and human brain.

Introduction

The genetic basis of human brain evolution is a central question in both neuroscience and human biology. In order to better understand both the neurobiology of modern humans and the evolutionary processes that produced the modern human brain, researchers from various fields have labored to identify and describe the shared genetic mechanisms that govern the neurodevelopment of all mammals, as well as the distinct developmental genetic differences that distinguish various species. The modern human brain is unique among all living primates in a number of ways, but the overall size of the cerebral hemispheres and the remarkable folding (gyrification) of the cerebral cortex are certainly among the most fundamental of human neuroanatomical features. A better understanding of the genetic mechanisms that govern overall brain size and the degree of cortical gyrification would have fundamental implications for both neuroscience and human evolutionary studies.

The history of primate brain evolution over the past 50 million years consists of progressive increase in both brain volume and gyrification. Early primates prior to 40 million years ago exhibited small brains with little or no cortical folding (Martin, 1990, Preuss, 2007). In more advanced primates such as the New World monkeys (e.g. marmosets or capuchins) and Old World monkeys (e.g. macaques and baboons), brain size is larger in absolute terms and especially as a fraction of body size (brain:body size ratio). This trend toward larger cerebral volume and greater brain:body size ratios (Fig. 1) was continued with the later appearance of the great apes (chimpanzees, gorillas and orangutans) (Kaas, 2008, Martin, 1990, Preuss, 2007). In parallel with the increase in brain volume, there has also been an increase in the degree of cortical folding (gyrification). In general, Old World monkeys have cerebral hemispheres with more significantly folded cerebral cortex than do New World monkeys, and the great apes show still more gyrification (Fig. 1). Thus, across the broad diversity of living primate species, there is a strong positive correlation between absolute brain volume and degree of gyrification. A similar relationship between brain size and gyrification is also observed in other orders of mammals, particularly cetaceans (Pillay and Manger, 2007). Since the human brain stands as the most extreme case of the parallel increase in these two traits among primates, constructing a more detailed understanding of the relevant genetic, developmental and evolutionary processes that produced this pattern of between-species differences will provide new insights into the processes that shaped human brain structure.

Recent research has shown that individual variation in brain volume within primate species is under strong genetic control. Various studies in humans and other primates have investigated the heritability (h2) of cerebral volume (i.e. the proportion of total phenotypic variation that can be accounted for by genetic differences among individuals), and reported estimates in the range of h2 = 0.5–0.8 or higher (Cheverud et al., 1990, Posthuma et al., 2002, Rogers et al., 2007, Thompson et al., 2001, Toga and Thompson, 2005). This indicates that 50%–80% or more of individual variation in brain volume is caused by genetic differences among subjects. Despite this evidence for genetic control of individual variation in brain volume, and the widely recognized correlation across species between brain volume and cortical folding, little is known about the influence of genetic differences on individual (within-species) variation in gyrification. The tight correlation between brain volume and cortical folding across primates as well as other mammals implies a degree of genetic control over gyrification that should not be difficult to detect. However, that genetic effect has not been clearly established either in humans or any other primate (Bartley et al., 1997, Lohmann et al., 1999, White et al., 2002).

We undertook this study to test two predictions. First, we predicted that like brain volume, individual variation within species in gyrification will exhibit additive genetic variance, i.e. heritability. Second, we anticipated that the same genes that influence individual variation in brain volume will also influence gyrification. We predicted that the genetic correlation (ρG) between these traits will be positive and substantial, possibly approaching unity (ρG = 1). We conducted our study in parallel in humans and baboons (Papio hamadryas). We used the same magnetic resonance imaging methods to quantify variation in cerebral gyrification among 97 baboons and 242 people. This two-species approach allowed us to simultaneously test our predictions in different species, and determine whether the genetic architecture of these traits is different in humans than in other primates. While brain size has increased throughout the last 45–50 million years of primate evolution, the human brain has undergone extremely rapid expansion during the last three million years (Barton, 2006, Kaas and Preuss, 2003, Schoenemann, 2006). This unique acceleration in our evolutionary lineage justifies independent assessments in humans and nonhuman primates because the genetic architecture of these traits may have been altered during that process of recent human brain expansion.

Section snippets

Study subjects

Structural MR images were collected for 97 pedigreed adult baboons (P. hamadryas) housed at the Southwest National Primate Research Center (San Antonio, TX). Animal handling protocols were described previously (Rogers et al., 2007). Study animals consisted of 46 males and 51 females, average age 15.2 ± 4.0 (s.d.) years (range: 7.3–27.3 years). Genealogical relationships included 276 parent–offspring pairs, 25 full sib pairs, 362 half-sib pairs, 172 grandparent–grandoffspring pairs and a large

Results

We find that the mean gyrification index (GI) for the external gray matter surface was GI = 1.89 ± 0.15 for baboons and GI = 2.29 ± 0.08 for humans. GI values calculated for different primate species appropriately matched the evolutionary trends in gyrification previously reported (Fig. 1). Neither age nor sex was significantly related to GI in baboons, while both age (p = 3.8 × 10 10) and sex (p = 2.4 × 10 4) were significantly related to GI in humans. Quantitative genetic analyses showed that brain volume,

Discussion

Early fossil primates older than 40 million years have small body sizes and small brain sizes, which reflect their recent divergence from other mammalian orders (Martin, 1990). One hallmark of primate evolutionary history is the origin of new species and new evolutionary groups that exhibit both increased body size and increased brain size relative to body size. As a result, the primate species living today exhibit a broad range of brain sizes and brain:body size ratios (Martin, 1990, Preuss,

Acknowledgments

This work was supported in part by grants from the US National Institute of Mental Health (MH078111, MH059490, and MH078143), the National Institute of Biomedical Imaging and Bioengineering (K01 EB006395) and the National Center for Research Resources base grant to the Southwest National Primate Research Center (P51-RR013986). We are grateful to the participants in the Genetics of Brain Structure Study. The supercomputing facilities used for this work at the AT&T Genetics Computing Center were

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    These two authors contributed equally to this paper.

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    Present address: Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

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