The genetic basis of neurocranial size and shape across varied lab mouse populations.

Brain and skull tissues interact through molecular signalling and mechanical forces during head development, leading to a strong correlation between the neurocranium and the external brain surface. Therefore, when brain tissue is unavailable, neurocranial endocasts are often used to approximate brain size and shape. Evolutionary changes in brain morphology may have resulted in secondary changes to neurocranial morphology, but the developmental and genetic processes underlying this relationship are not well understood. Using automated phenotyping methods, we quantified the genetic basis of endocast variation across large genetically varied populations of laboratory mice in two ways: (1) to determine the contributions of various genetic factors to neurocranial form and (2) to help clarify whether a neurocranial variation is based on genetic variation that primarily impacts bone development or on genetic variation that primarily impacts brain development, leading to secondary changes in bone morphology. Our results indicate that endocast size is highly heritable and is primarily determined by additive genetic factors. In addition, a non-additive inbreeding effect led to founder strains with lower neurocranial size, but relatively large brains compared to skull size; suggesting stronger canalization of brain size and/or a general allometric effect. Within an outbred sample of mice, we identified a locus on mouse chromosome 1 that is significantly associated with variation in several positively correlated endocast size measures. Because the protein-coding genes at this locus have been previously associated with brain development and not with bone development, we propose that genetic variation at this locus leads primarily to variation in brain volume that secondarily leads to changes in neurocranial globularity. We identify a strain-specific missense mutation within Akt3 that is a strong causal candidate for this genetic effect. Whilst it is not appropriate to generalize our hypothesis for this single locus to all other loci that also contribute to the complex trait of neurocranial skull morphology, our results further reveal the genetic basis of neurocranial variation and highlight the importance of the mechanical influence of brain growth in determining skull morphology.

Secular changes in body height predict global rates of caesarean section.

The massive global variation in caesarean-section (C-section) rate is usually attributed to socio-economic, medical and cultural heterogeneity. Here, we show that a third of the global variance in current national C-section rate can be explained by the trends of adult body height from the 1970s to the 1990s. In many countries, living conditions have continually improved during the last century, which has led to an increase in both fetal and adult average body size. As the fetus is one generation ahead of the mother, the fetus is likely to experience better environmental conditions during development than the mother did, causing a disproportionately large fetus and an increased risk of obstructed labour. A structural equation model revealed that socio-economic development and access to healthcare affect C-section rate via multiple causal pathways, but the strongest direct effect on C-section rate was body height change. These results indicate that the historical trajectory of socio-economic development affects-via its influence on pre- and postnatal growth-the intergenerational relationship between maternal and fetal dimensions and thus the difficulty of labour. This sheds new light on historic and prehistoric transitions of childbirth and questions the World Health Organization (WHO) suggestion for a global 'ideal' C-section rate.

Sex differences in the pelvis did not evolve de novo in modern humans.

It is commonly assumed that the strong sexual dimorphism of the human pelvis evolved for delivering the relatively large human foetuses. Here we compare pelvic sex differences across modern humans and chimpanzees using a comprehensive geometric morphometric approach. Even though the magnitude of sex differences in pelvis shape was two times larger in humans than in chimpanzees, we found that the pattern is almost identical in the two species. We conclude that this pattern of pelvic sex differences did not evolve de novo in modern humans and must have been present in the common ancestor of humans and chimpanzees, and thus also in the extinct Homo species. We further suggest that this shared pattern was already present in early mammals and propose a hypothesis of facilitated variation as an explanation: the conserved mammalian endocrine system strongly constrains the evolution of the pattern of pelvic differences but enables rapid evolutionary change of the magnitude of sexual dimorphism, which in turn facilitated the rapid increase in hominin brain size.