Evidence of a Conserved Molecular Response to Selection for Increased Brain Size in Primates

The adaptive significance of human brain evolution has been frequently studied through comparisons with other primates. However, the evolution of increased brain size is not restricted to the human lineage but is a general characteristic of primate evolution. Whether or not these independent episodes of increased brain size share a common genetic basis is unclear. We sequenced and de novo assembled the transcriptome from the neocortical tissue of the most highly encephalized nonhuman primate, the tufted capuchin monkey ($\textit{Cebus apella}$). Using this novel data set, we conducted a genome-wide analysis of orthologous brain-expressed protein coding genes to identify evidence of conserved gene-phenotype associations and species-specific adaptations during three independent episodes of brain size increase. We identify a greater number of genes associated with either total brain mass or relative brain size across these six species than show species-specific accelerated rates of evolution in individual large-brained lineages. We test the robustness of these associations in an expanded data set of 13 species, through permutation tests and by analyzing how genome-wide patterns of substitution co-vary with brain size. Many of the genes targeted by selection during brain expansion have glutamatergic functions or roles in cell cycle dynamics. We also identify accelerated evolution in a number of individual capuchin genes whose human orthologs are associated with human neuropsychiatric disorders. These findings demonstrate the value of phenotypically informed genome analyses, and suggest at least some aspects of human brain evolution have occurred through conserved gene-phenotype associations. Understanding these commonalities is essential for distinguishing human-specific selection events from general trends in brain evolution.This work was supported by the National Science Foundation, grant award numbers BCS-0751508, BCS-0827546, and BCS-1061370 for AMB and DEW. Professor Chet Sherwood (The George Washington University) provided useful guidance in the initial stages of this project. S.H.M. is grateful for support from a BBSRC doctoral training grant and a Research Fellowship from the Royal Commission for the Exhibition of 1851. N.I.M. is grateful for support from the Leverhulme Trust and Murray Edwards College, Cambridge

Gradients in cytoarchitectural landscapes of the isocortex: Diprotodont marsupials in comparison to eutherian mammals

Although it has been claimed that marsupials possess a lower density of isocortical neurons compared with other mammals, little is known about cross‐cortical variation in neuron distributions in this diverse taxonomic group. We quantified upper‐layer (layers II–IV) and lower‐layer (layers V–VI) neuron numbers per unit of cortical surface area in three diprotodont marsupial species (two macropodiformes, the red kangaroo and the parma wallaby, and a vombatiform, the koala) and compared these results to eutherian mammals (e.g., xenarthrans, rodents, primates). In contrast to the notion that the marsupial isocortex contains a low density of neurons, we found that neuron numbers per unit of cortical surface area in several marsupial species overlap with those found in eutherian mammals. Furthermore, neuron numbers vary systematically across the isocortex of the marsupial mammals examined. Neuron numbers under a unit of cortical surface area are low toward the frontal cortex and high toward the caudo‐medial (occipital) pole. Upper‐layer neurons (i.e., layers II–IV) account for most of the variation in neuron numbers across the isocortex. The variation in neuron numbers across the rostral to the caudal pole resembles primates. These findings suggest that diprotodont marsupials and eutherian mammals share a similar cortical architecture despite their distant evolutionary divergence

Dopamine acting at D1-like, D2-like and α1-adrenergic receptors differentially modulates theta and gamma oscillatory activity in primary motor cortex

The loss of dopamine (DA) in Parkinson’s is accompanied by the emergence of exaggerated theta and beta frequency neuronal oscillatory activity in the primary motor cortex (M1) and basal ganglia. DA replacement therapy or deep brain stimulation reduces the power of these oscillations and this is coincident with an improvement in motor performance implying a causal relationship. Here we provide in vitro evidence for the differential modulation of theta and gamma activity in M1 by DA acting at receptors exhibiting conventional and non-conventional DA pharmacology. Recording local field potentials in deep layer V of rat M1, co-application of carbachol (CCh, 5 μM) and kainic acid (KA, 150 nM) elicited simultaneous oscillations at a frequency of 6.49 ± 0.18 Hz (theta, n = 84) and 34.97 ± 0.39 Hz (gamma, n = 84). Bath application of DA resulted in a decrease in gamma power with no change in theta power. However, application of either the D1-like receptor agonist SKF38393 or the D2-like agonist quinpirole increased the power of both theta and gamma suggesting that the DA-mediated inhibition of oscillatory power is by action at other sites other than classical DA receptors. Application of amphetamine, which promotes endogenous amine neurotransmitter release, or the adrenergic α1-selective agonist phenylephrine mimicked the action of DA and reduced gamma power, a result unaffected by prior co-application of D1 and D2 receptor antagonists SCH23390 and sulpiride. Finally, application of the α1-adrenergic receptor antagonist prazosin blocked the action of DA on gamma power suggestive of interaction between α1 and DA receptors. These results show that DA mediates complex actions acting at dopamine D1-like and D2-like receptors, α1 adrenergic receptors and possibly DA/α1 heteromultimeric receptors to differentially modulate theta and gamma activity in M1

Human Evolution and the Chimpanzee Referential Doctrine

Chimpanzees are our closest living genomic relatives, but they lack the bipedal locomotion, markedly enlarged brains, and advanced communication skills of humans. This has led many to view them as “primitive” and to presume that their behavior and anatomy are also primitive. If true, they could serve as models of our last common ancestor (LCA), i.e., a territorially aggressive knuckle walker, reliant on vertical climbing and below-branch suspension to access the high canopy as a ripe-fruit frugivore. Ardipithecus now provides abundant information that the LCA differed substantially from chimpanzees (as well as bonobos and gorillas), both anatomically and behaviorally, and exhibited many characters that are more similar to those of modern humans than to any living ape. This major extension of the hominoid fossil record contravenes strict referential modeling based on the extant chimpanzee and greatly improves our ability to reconstruct the LCA more accurately, but only when viewed within the broader context of evolutionary ecology