Adaptive evolution of four microcephaly genes and the evolution of brain size in anthropoid primates

The anatomical basis and adaptive function of the expansion in primate brain size have long been studied; however, we are only beginning to understand the genetic basis of these evolutionary changes. Genes linked to human primary microcephaly have received much attention as they have accelerated evolutionary rates along lineages leading to humans. However, these studies focus narrowly on apes, and the link between microcephaly gene evolution and brain evolution is disputed. We analyzed the molecular evolution of four genes associated with microcephaly (ASPM, CDK5RAP2, CENPJ, MCPH1) across 21 species representing all major clades of anthropoid primates. Contrary to prevailing assumptions, positive selection was not limited to or intensified along the lineage leading to humans. In fact we show that all four loci were subject to positive selection across the anthropoid primate phylogeny. We developed clearly defined hypotheses to explicitly test if selection on these loci was associated with the evolution of brain size. We found positive relationships between both CDK5RAP2 and ASPM and neonatal brain mass and somewhat weaker relationships between these genes and adult brain size. In contrast, there is no evidence linking CENPJ and MCPH1 to brain size evolution. The stronger association of ASPM and CDK5RAP2 evolution with neonatal brain size than with adult brain size is consistent with these loci having a direct effect on prenatal neuronal proliferation. These results suggest that primate brain size may have at least a partially conserved genetic basis. Our results contradict a previous study that linked adaptive evolution of ASPM to changes in relative cortex size; however, our analysis indicates that this conclusion is not robust. Our finding that the coding regions of two widely expressed loci has experienced pervasive positive selection in relation to a complex, quantitative developmental phenotype provides a notable counterexample to the commonly asserted hypothesis that cisregulatory regions play a dominant role in phenotypic evolution. Key words: ASPM, MCPH1, CDK5RAP2, CENPJ, brain, neurogenesis, primates.

Larger brain size indirectly increases vulnerability to extinction in mammals

Although previous studies have addressed the question of why large brains evolved, we have limited understanding of potential beneficial or detrimental effects of enlarged brain size in the face of current threats. Using novel phylogenetic path analysis, we evaluated how brain size directly and indirectly, via its effects on life-history and ecology, influences vulnerability to extinction across 474 mammalian species. We found that larger brains, controlling for body size, indirectly increase vulnerability to extinction by extending the gestation period, increasing weaning age, and limiting litter sizes. However, we found no evidence of direct, beneficial or detrimental, effects of brain size on vulnerability to extinction, even when we explicitly considered the different types of threats that lead to vulnerability. Order-specific analyses revealed qualitatively similar patterns for Carnivora and Artiodactyla. Interestingly, for Primates, we found that larger brain size was directly (and indirectly) associated with increased vulnerability to extinction. Our results indicate that under current conditions the constraints on life-history imposed by large brains outweigh the potential benefits, undermining the resilience of the studied mammals. Contrary to the selective forces that have favoured increased brain size throughout evolutionary history, at present, larger brains have become a burden for mammals.

Placentation and maternal investment in mammals

The mammalian placenta exhibits striking interspecific morphological variation, yet the implications of such diversity for reproductive strategies and fetal development remain obscure. More invasive hemochorial placentas, in which fetal tissues directly contact the maternal blood supply, are believed to facilitate nutrient transfer, resulting in higher fetal growth rates, and to be a state of relative fetal advantage in the evolution of maternal-offspring conflict. The extent of interdigitation between maternal and fetal tissues has received less attention than invasiveness but is also potentially important because it influences the surface area for exchange. We show that although increased placental invasiveness and interdigitation are both associated with shorter gestations, interdigitation is the key variable. Gestation times associated with highly interdigitated labyrinthine placentas are 44% of those associated with less interdigitated villous and trabecular placentas. There is, however, no relationship between placental traits and neonatal body and brain size. Hence, species with more interdigitated placentas produce neonates of similar body and brain size but in less than half the time. We suggest that the effects of placental interdigitation on growth rates and the way that these are traded off against gestation length may be promising avenues for understanding the evolutionary dynamics of parentoffspring conflict. Keywords: placenta, parent-offspring conflict, life history, brain evolution, reproductive strategies, gestation.

Human frontal lobes are not relatively large

One of the most pervasive assumptions about human brain evolution is that it involved relative enlargement of the frontal lobes. We show that this assumption is without foundation. Analysis of five independent data sets using correctly scaled measures and phylogenetic methods reveals that the size of human frontal lobes, and of specific frontal regions, is as expected relative to the size of other brain structures. Recent claims for relative enlargement of human frontal white matter volume, and for relative enlargement shared by all great apes, seem to be mistaken. Furthermore, using a recently developed method for detecting shifts in evolutionary rates, we find that the rate of change in relative frontal cortex volume along the phylogenetic branch leading to humans was unremarkable and that other branches showed significantly faster rates of change. Although absolute and proportional frontal region size increased rapidly in humans, this change was tightly correlated with corresponding size increases in other areas andwhole brain size, and with decreases in frontal neuron densities. The search for the neural basis of human cognitive uniqueness should therefore focus less on the frontal lobes in isolation and more on distributed neural networks.

Watching the infant brain learn words: Effects of vocabulary size and experience

Previous investigations comparing auditory event-related potentials (ERPs) to words whose meanings infants did or did not comprehend, found bilateral differences in brain activity to known versus unknown words in 13-month-old infants, in contrast with unilateral, left hemisphere, differences in activity in 20-month-old infants. We explore two alternative explanations for these findings. Changes in hemispheric specialization may result from a qualitative shift in the way infants process known words between 13 and 20 months. Alternatively, hemispheric specialization may arise from increased familiarity with the individual words tested. We contrasted these two explanations by measuring ERPs from 20-month-old infants with high and low production scores, for novel words they had just learned. A bilateral distribution of ERP differences was observed in both groups of infants, though the difference was larger in the left hemisphere for the high producers. These findings suggest that word familiarity is an important factor in determining the distribution of brain regions involved in word learning. An emerging left hemispheric specialization may reflect increased efficiency in the manner in which infants process familiar and novel words. (c) 2004 Elsevier Inc. All rights reserved.

Organizational effects of fetal testosterone on human corpus callosum size and asymmetry

Previous theory and research in animals has identified the critical role that fetal testosterone (FT) plays in organizing sexually dimorphic brain development. However, to date there are no studies in humans directly testing the organizational effects of FT on structural brain development. In the current study we investigated the effects of FT on corpus callosum size and asymmetry. High-resolution structural magnetic resonance images (MRI) of the brain were obtained on 28 8-11-year-old boys whose exposure to FT had been previously measured in utero via amniocentesis conducted during the second trimester. Although there was no relationship between FT and midsaggital corpus callosum size, increasing FT was significantly related to increasing rightward asymmetry (e.g., Right>Left) of a posterior subsection of the callosum, the isthmus, that projects mainly to parietal and superior temporal areas. This potential organizational effect of FT on rightward callosal asymmetry may be working through enhancing the neuroprotective effects of FT and result in an asymmetric distribution of callosal axons. We suggest that this possible organizational effect of FT on callosal asymmetry may also play a role in shaping sexual dimorphism in functional and structural brain development, cognition, and behavior.