Despite a general trend for larger mammals to have larger brains, humans are the primates with the largest brain and number of neurons, but not the largest body mass. Why are great apes, the largest primates, not also those endowed with the largest brains? Recently, we showed that the energetic cost of the brain is a linear function of its numbers of neurons. Here we show that metabolic limitations that result from the number of hours available for feeding and the low caloric yield of raw foods impose a tradeoff between body size and number of brain neurons, which explains the small brain size of great apes compared with their large body size. This limitation was probably overcome in Homo erectus with the shift to a cooked diet. Absent the requirement to spend most available hours of the day feeding, the combination of newly freed time and a large number of brain neurons affordable on a cooked diet may thus have been a major positive driving force to the rapid increased in brain size in human evolution.encephalization | expensive tissue hypothesis | brain metabolism T he human brain is a linearly scaled-up primate brain in its relationship between brain size and number of neurons (1), having evolved while being subjected to the same cellular scaling rules that apply to primates as a whole (2, 3), including great apes (4). With the largest brain among primates, humans thus have the largest number of neurons among these and possibly all mammals (5), a number that we estimate to be close to three times larger than in gorillas and orangutans, owners of the next largest brains among extant primates (4). We are not outstanding primates, on the contrary, in body size: gorillas can grow to be three times larger than humans. This discrepancy between body and brain size led to the predominant view that encephalization (that is, a larger brain size than expected for body size) is the main characteristic that sets humans apart from other primates and mammals as a whole (6). Although a relatively large brain compared with body size is expected to bring cognitive advantages (6), and despite the well-documented evidence for an increase in brain size during human evolution (7), there is still no consensus on what mechanisms or reasons led to brain enlargement in the Homo lineage.Why are the largest primates not those endowed with the largest brains as well? Rather than evidence that humans are an exception among primates, we consider this disparity to be a clue that, in primate evolution, developing a very large body and a very large brain have been mutually excluding strategies, probably because of metabolic reasons (4, 8). The brain is the third most energy-expensive organ in the human body, ranking in total organ metabolic cost below only skeletal muscle and liver (9). Accordingly, several studies have suggested that the main constraints to increasing primate brain size in evolution are metabolic in nature (10-18). The human brain, in particular, has come to cost ∼20% of the total body resting metabolic rate, even though it ...

There is a strong trend toward increased brain size in mammalian evolution, with larger brains composed of more and larger neurons than smaller brains across species within each mammalian order. Does the evolution of increased numbers of brain neurons, and thus larger brain size, occur simply through the selection of individuals with more and larger neurons, and thus larger brains, within a population? That is, do individuals with larger brains also have more, and larger, neurons than individuals with smaller brains, such that allometric relationships across species are simply an extension of intraspecific scaling? Here we show that this is not the case across adult male mice of a similar age. Rather, increased numbers of neurons across individuals are accompanied by increased numbers of other cells and smaller average cell size of both types, in a trade-off that explains how increased brain mass does not necessarily ensue. Fundamental regulatory mechanisms thus must exist that tie numbers of neurons to numbers of other cells and to average cell size within individual brains. Finally, our results indicate that changes in brain size in evolution are not an extension of individual variation in numbers of neurons, but rather occur through step changes that must simultaneously increase numbers of neurons and cause cell size to increase, rather than decrease.