Dairying, diseases and the evolution of lactase persistence in Europe.

In European and many African, Middle Eastern and southern Asian populations, lactase persistence (LP) is the most strongly selected monogenic trait to have evolved over the past 10,000 years1. Although the selection of LP and the consumption of prehistoric milk must be linked, considerable uncertainty remains concerning their spatiotemporal configuration and specific interactions2,3. Here we provide detailed distributions of milk exploitation across Europe over the past 9,000 years using around 7,000 pottery fat residues from more than 550 archaeological sites. European milk use was widespread from the Neolithic period onwards but varied spatially and temporally in intensity. Notably, LP selection varying with levels of prehistoric milk exploitation is no better at explaining LP allele frequency trajectories than uniform selection since the Neolithic period. In the UK Biobank4,5 cohort of 500,000 contemporary Europeans, LP genotype was only weakly associated with milk consumption and did not show consistent associations with improved fitness or health indicators. This suggests that other reasons for the beneficial effects of LP should be considered for its rapid frequency increase. We propose that lactase non-persistent individuals consumed milk when it became available but, under conditions of famine and/or increased pathogen exposure, this was disadvantageous, driving LP selection in prehistoric Europe. Comparison of model likelihoods indicates that population fluctuations, settlement density and wild animal exploitation-proxies for these drivers-provide better explanations of LP selection than the extent of milk exploitation. These findings offer new perspectives on prehistoric milk exploitation and LP evolution.

The paradox of Prader-Willi syndrome revisited: Making sense of the phenotype.

Prader-Willi syndrome arises as a consequence of absent paternal copies of maternally imprinted genes at 15q11-13. Such gender-of-origin imprinted genes are expressed in the brain and also in mammalian placenta where paternally expressed imprinted genes drive foetal nutritional demand. We hypothesise that the PWS phenotype is the result of the genotype impacting two pathways: first, directly on brain development and secondly, on placental nutritional pathways that results in its down-regulation and relative foetal starvation. The early PWS phenotype establishes the basis for the later characteristic phenotype. Hyperphagia. and other phenotypic characteristics arise as a consequence of impaired hypothalamic development. Hypothalamic feeding pathways become set in a state indicative of starvation, with a high satiety threshold and a dysfunctional neurophysiological state due to incorrect representations of reward needs, based on inputs that indicate a false requirement for food. Our hypotheses, if confirmed, would lead to novel and effective interventions.

t-VNS to treat disorders of behaviour in Prader-Willi Syndrome and in people with other neurodevelopmental conditions.

This paper proposes that tVNS has the potential to be a new treatment for some of the behaviour difficulties that may affect people with intellectual disabilities and/or autism, particularly those people born with specific neurodevelopmental syndromes. Behaviours, such as emotional outbursts, physical aggression, and self-injury are a relative common occurrence in these groups and have a significant impact on wellbeing and quality of life for the individuals and their families. Such behaviours have generally been understood through the lens of learning theory, the likelihood of their occurrence being shaped and reinforced by the responses of others. However, when vagus nerve stimulation has been used to treat epilepsy improvements in cognition, behaviour, and general wellbeing have been noted suggesting that with these behaviours other causal mechanisms are also important. More recently incidental findings from a proof of concept study where vagus nerve stimulation was given, using an implanted device, to people with the genetically determined neurodevelopmental disorder, Prader-Willi Syndrome (PWS), findings of benefit supported the above view. A second study, this time using tVNS, reported a similar result. In this paper we review the evidence for the use of tVNS for behavioural problems, consider the challenges when conducting trials in this population, and reflect on what the preliminary observations in people with PWS tell us about the possible mechanisms that underpin such behaviours.

Directly modelling population dynamics in the South American Arid Diagonal using 14C dates.

Large anthropogenic 14C datasets are widely used to generate summed probability distributions (SPDs) as a proxy for past human population levels. However, SPDs are a poor proxy when datasets are small, bearing little relationship to true population dynamics. Instead, more robust inferences can be achieved by directly modelling the population and assessing the model likelihood given the data. We introduce the R package ADMUR which uses a continuous piecewise linear (CPL) model of population change, calculates the model likelihood given a 14C dataset, estimates credible intervals using Markov chain Monte Carlo, applies a goodness-of-fit test, and uses the Schwarz Criterion to compare CPL models. We demonstrate the efficacy of this method using toy data, showing that spurious dynamics are avoided when sample sizes are small, and true population dynamics are recovered as sample sizes increase. Finally, we use an improved 14C dataset for the South American Arid Diagonal to compare CPL modelling to current simulation methods, and identify three Holocene phases when population trajectory estimates changed from rapid initial growth of 4.15% per generation to a decline of 0.05% per generation between 10 821 and 7055 yr BP, then gently grew at 0.58% per generation until 2500 yr BP. This article is part of the theme issue 'Cross-disciplinary approaches to prehistoric demography'.

Pastoralism may have delayed the end of the green Sahara.

The climate deterioration after the most recent African humid period (AHP) is a notable past example of desertification. Evidence points to a human population expansion in northern Africa prior to this, associated with the introduction of pastoralism. Here we consider the role, if any, of this population on the subsequent ecological collapse. Using a climate-vegetation model, we estimate the natural length of the most recent AHP. The model indicates that the system was most susceptible to collapse between 7 and 6 ka; at least 500 years before the observed collapse. This suggests that the inclusion of increasing elements of pastoralism was an effective adaptation to the regional environmental changes. Pastoralism also appears to have slowed the deterioration caused by orbitally-driven climate change. This supports the view that modern pastoralism is not only sustainable, but beneficial for the management of the world's dryland environments.

Size Reduction in Early European Domestic Cattle Relates to Intensification of Neolithic Herding Strategies.

Our analysis of over 28,000 osteometric measurements from fossil remains dating between c. 5600 and 1500 BCE reveals a substantial reduction in body mass of 33% in Neolithic central European domestic cattle. We investigate various plausible explanations for this phenotypic adaptation, dismissing climatic change as a causal factor, and further rejecting the hypothesis that it was caused by an increase in the proportion of smaller adult females in the population. Instead we find some support for the hypothesis that the size decrease was driven by a demographic shift towards smaller newborns from sub-adult breeding as a result of intensifying meat production strategies during the Neolithic.

Regional population collapse followed initial agriculture booms in mid-Holocene Europe.

Following its initial arrival in SE Europe 8,500 years ago agriculture spread throughout the continent, changing food production and consumption patterns and increasing population densities. Here we show that, in contrast to the steady population growth usually assumed, the introduction of agriculture into Europe was followed by a boom-and-bust pattern in the density of regional populations. We demonstrate that summed calibrated radiocarbon date distributions and simulation can be used to test the significance of these demographic booms and busts in the context of uncertainty in the radiocarbon date calibration curve and archaeological sampling. We report these results for Central and Northwest Europe between 8,000 and 4,000 cal. BP and investigate the relationship between these patterns and climate. However, we find no evidence to support a relationship. Our results thus suggest that the demographic patterns may have arisen from endogenous causes, although this remains speculative.