Large-scale functional screen identifies genetic variants with splicing effects in modern and archaic humans.

Humans coexisted and interbred with other hominins which later became extinct. These archaic hominins are known to us only through fossil records and for two cases, genome sequences. Here, we engineer Neanderthal and Denisovan sequences into thousands of artificial genes to reconstruct the pre-mRNA processing patterns of these extinct populations. Of the 5,169 alleles tested in this massively parallel splicing reporter assay (MaPSy), we report 962 exonic splicing mutations that correspond to differences in exon recognition between extant and extinct hominins. Using MaPSy splicing variants, predicted splicing variants, and splicing quantitative trait loci, we show that splice-disrupting variants experienced greater purifying selection in anatomically modern humans than that in Neanderthals. Adaptively introgressed variants were enriched for moderate-effect splicing variants, consistent with positive selection for alternative spliced alleles following introgression. As particularly compelling examples, we characterized a unique tissue-specific alternative splicing variant at the adaptively introgressed innate immunity gene TLR1, as well as a unique Neanderthal introgressed alternative splicing variant in the gene HSPG2 that encodes perlecan. We further identified potentially pathogenic splicing variants found only in Neanderthals and Denisovans in genes related to sperm maturation and immunity. Finally, we found splicing variants that may contribute to variation among modern humans in total bilirubin, balding, hemoglobin levels, and lung capacity. Our findings provide unique insights into natural selection acting on splicing in human evolution and demonstrate how functional assays can be used to identify candidate causal variants underlying differences in gene regulation and phenotype.

MaLAdapt Reveals Novel Targets of Adaptive Introgression From Neanderthals and Denisovans in Worldwide Human Populations.

Adaptive introgression (AI) facilitates local adaptation in a wide range of species. Many state-of-the-art methods detect AI with ad-hoc approaches that identify summary statistic outliers or intersect scans for positive selection with scans for introgressed genomic regions. Although widely used, approaches intersecting outliers are vulnerable to a high false-negative rate as the power of different methods varies, especially for complex introgression events. Moreover, population genetic processes unrelated to AI, such as background selection or heterosis, may create similar genomic signals to AI, compromising the reliability of methods that rely on neutral null distributions. In recent years, machine learning (ML) methods have been increasingly applied to population genetic questions. Here, we present a ML-based method called MaLAdapt for identifying AI loci from genome-wide sequencing data. Using an Extra-Trees Classifier algorithm, our method combines information from a large number of biologically meaningful summary statistics to capture a powerful composite signature of AI across the genome. In contrast to existing methods, MaLAdapt is especially well-powered to detect AI with mild beneficial effects, including selection on standing archaic variation, and is robust to non-AI selective sweeps, heterosis from deleterious mutations, and demographic misspecification. Furthermore, MaLAdapt outperforms existing methods for detecting AI based on the analysis of simulated data and the validation of empirical signals through visual inspection of haplotype patterns. We apply MaLAdapt to the 1000 Genomes Project human genomic data and discover novel AI candidate regions in non-African populations, including genes that are enriched in functionally important biological pathways regulating metabolism and immune responses.

Skin colour: A window into human phenotypic evolution and environmental adaptation.

As modern humans ventured out of Africa and dispersed around the world, they faced novel environmental challenges that led to geographic adaptations including skin colour. Over the long history of human evolution, skin colour has changed dramatically, showing tremendous diversity across different geographical regions, for example, the majority of individuals from the expansive lands of Africa have darker skin, whereas the majority of people from Eurasia exhibit lighter skin. What adaptations did lighter skin confer upon modern humans as they migrated from Africa to Eurasia? What genetic mechanisms underlie the diversity of skin colour observed in different populations? In recent years, scientists have gradually gained a deeper understanding of the interactions between pigmentation gene and skin colour through population-based genomic studies of different groups around the world, particularly in East Asia and Africa. In this review, we summarize our current understanding of 26 skin colour-related pigmentation genes and 48 SNPs that influence skin colour. Important pigmentation genes across three major populations are described in detail: MFSD12, SLC24A5, PDPK1 and DDB1/CYB561A3/TMEM138 influence skin colour in African populations; OCA2, KITLG, SLC24A2, GNPAT and PAH are key to the evolution of skin pigmentation in East Asian populations; and SLC24A5, SLC45A2, TYR, TYRP1, ASIP, MC1R and IRF4 significantly contribute to the lightening of skin colour in European populations. We summarized recent findings in genomic studies of skin colour in populations that implicate diverse geographic environments, local adaptation among populations, gene flow and multi-gene interactions as factors influencing skin colour diversity.

Ancient DNA and multimethod dating confirm the late arrival of anatomically modern humans in southern China.

The expansion of anatomically modern humans (AMHs) from Africa around 65,000 to 45,000 y ago (ca. 65 to 45 ka) led to the establishment of present-day non-African populations. Some paleoanthropologists have argued that fossil discoveries from Huanglong, Zhiren, Luna, and Fuyan caves in southern China indicate one or more prior dispersals, perhaps as early as ca. 120 ka. We investigated the age of the human remains from three of these localities and two additional early AMH sites (Yangjiapo and Sanyou caves, Hubei) by combining ancient DNA (aDNA) analysis with a multimethod geological dating strategy. Although U-Th dating of capping flowstones suggested they lie within the range ca. 168 to 70 ka, analyses of aDNA and direct AMS 14C dating on human teeth from Fuyan and Yangjiapo caves showed they derive from the Holocene. OSL dating of sediments and AMS 14C analysis of mammal teeth and charcoal also demonstrated major discrepancies from the flowstone ages; the difference between them being an order of magnitude or more at most of these localities. Our work highlights the surprisingly complex depositional history recorded at these subtropical caves which involved one or more episodes of erosion and redeposition or intrusion as recently as the late Holocene. In light of our findings, the first appearance datum for AMHs in southern China should probably lie within the timeframe set by molecular data of ca. 50 to 45 ka.

Long-term occlusal tooth wear at the onset of permanent dentition.

OBJECTIVES: This study quantified the long-term occlusal wear in the natural posterior teeth and the associations per tooth type within the dentition. METHODS: The sample included 70 orthodontically treated subjects (52 females and 18 males; median age, 14.3 years), followed for a 12.7-year period. They were consecutively selected with no tooth wear-related criteria. Post-treatment (T1) and follow-up dental casts (T2) were scanned and superimposed through three-dimensional methods. Occlusal wear volume of posterior teeth and tooth wear patterns were investigated through non-parametric statistics and analysis of covariance. RESULTS: There were no significant differences between contralateral teeth. The average occlusal wear per posterior tooth was 2.3 mm3, with 65.2% of teeth showing values greater than 1 mm3. Males, mandibular teeth, and first molars exhibited slightly greater wear levels than females (median, 2.57 and 2.21 mm3, respectively; p = 0.005), maxillary teeth, and first or second premolars, respectively. In all first premolars and in the mandibular second premolars, the buccal cusps were primarily affected with no other distinct patterns. There were weak to moderate correlations between tooth types, apart from certain strong correlations detected in males. CONCLUSIONS: Posterior tooth wear was highly prevalent after a 13-year period starting at the onset of permanent dentition. The detected patterns are in accordance with the concept of canine guidance occlusion that is transforming into group synergy through function. CLINICAL RELEVANCE: The widespread tooth wear occurrence and the high intra- and inter-individual variability underline the need for individual patient monitoring to identify high-risk patients at early stages.

New insights into the variability of upper airway morphology in modern humans.

The biological adaptation of the human lineage to its environment is a recurring question in paleoanthropology. Particularly, how eco-geographic factors (e.g., environmental temperature and humidity) have shaped upper airway morphology in hominins have been subject to continuing debate. Nasal shape is the result of many intertwined factors that include, but are not limited to, genetic drift, sexual selection, or adaptation to climate. A quantification of nasal airway (NA) morphological variation in modern human populations is crucial to better understand these multiple factors. In the present research, we study 195 in vivo CT scans of adult individuals collected in five different geographic areas (Chile, France, Cambodia, Russia, and South Africa). After segmentation of the nasal airway, we reconstruct 3D meshes that are analyzed with a landmark-free geometric morphometrics method based on surface deformation. Our results highlight subtle but statistically significant morphological differences between our five samples. The two morphologically closest groups are France and Russia, whose NAs are longer and narrower, with an important protrusion of the supero-anterior part. The Cambodian sample is the most morphologically distinct and clustered sample, with a mean NA that is wider and shorter. On the contrary, the Chilean sample form the most scattered cluster with the greatest intra-population variation. The South African sample is morphologically close to the Cambodian sample, but also partially overlaps the French and Russian variation. Interestingly, we record no correlation between NA volume and geographic groups, which raises the question of climate-related metabolic demands for oxygen consumption. The other factors of variation (sex and age) have no influence on the NA shape in our samples. However, NA volume varies significantly according both to sex and age: it is higher in males than in females and tends to increase with age. In contrast, we observe no effect of temperature or humidity on NA volume. Finally, we highlight the important influence of asymmetries related to nasal septum deviations in NA shape variation.

A new chronological framework for Chuandong Cave and its implications for the appearance of modern humans in southern China.

Chuandong Cave is an important Late Paleolithic site because it documents the early appearance of bone tools in southern China. We used the single-aliquot regenerative-dose protocol for optically stimulated luminescence dating to improve the precision of the chronology for the Chuandong Cave sedimentary sequence. The age of each layer was determined using a Bayesian modeling approach which combined optically stimulated luminescence ages with published AMS 14C dates. The results showed that Layer 10 began accumulating since 56 ± 14 ka and provides the upper age limit for all artifacts from the sequence. Bone awl tools from Layer 8, the earliest grinding bone tools in this site, were recovered within sediments between 40 ± 7 ka and 30 ± 4 ka. Layer 8 also indicates the appearance of modern humans in the Chuandong Cave sequence. Layers 4-2, ranging from 15 ± 3 ka until 11 ± 1 ka and including the Younger Dryas period, contain a few bone awls and an eyed bone needle. The shift from bone awls to eyed bone needles in the Chuandong Cave sequence indicates that modern humans adapted to the changing climate of southern China. We conclude that modern human behavior in bone tools appeared in southern China as early as 40 ± 7 ka, became more sophisticated during the Last Glacial Maximum, and spread more widely across southern China during the Younger Dryas.

The revolution that still isn't: The origins of behavioral complexity in Homo sapiens.

The behavioral origins of Homo sapiens can be traced back to the first material culture produced by our species in Africa, the Middle Stone Age (MSA). Beyond this broad consensus, the origins, patterns, and causes of behavioral complexity in modern humans remain debated. Here, we consider whether recent findings continue to support popular scenarios of: (1) a modern human 'package,' (2) a gradual and 'pan-African' emergence of behavioral complexity, and (3) a direct connection to changes in the human brain. Our geographically structured review shows that decades of scientific research have continuously failed to find a discrete threshold for a complete 'modernity package' and that the concept is theoretically obsolete. Instead of a continent-wide, gradual accumulation of complex material culture, the record exhibits a predominantly asynchronous presence and duration of many innovations across different regions of Africa. The emerging pattern of behavioral complexity from the MSA conforms to an intricate mosaic characterized by spatially discrete, temporally variable, and historically contingent trajectories. This archaeological record bears no direct relation to a simplistic shift in the human brain but rather reflects similar cognitive capacities that are variably manifested. The interaction of multiple causal factors constitutes the most parsimonious explanation driving the variable expression of complex behaviors, with demographic processes such as population structure, size, and connectivity playing a key role. While much emphasis has been given to innovation and variability in the MSA record, long periods of stasis and a lack of cumulative developments argue further against a strictly gradualistic nature in the record. Instead, we are confronted with humanity's deep, variegated roots in Africa, and a dynamic metapopulation that took many millennia to reach the critical mass capable of producing the ratchet effect commonly used to define contemporary human culture. Finally, we note a weakening link between 'modern' human biology and behavior from around 300 ka ago.

The protoconid: a key cusp in lower molars. Evidence from a recent modern human population.

BACKGROUND: The molar (M) size sequence in the genus Homo is decreasing and the general pattern in Homo sapiens is M1> M2 > M3. AIM: To gain a better understanding of the reduction patterns of M components (cusps), we aim to assess the area of the protoconid (Prd), the phylogenetically oldest cusp of the lower Ms. SUBJECT AND METHODS: We measured the Prd and the total crown area in the scaled photographs of a recent modern human sample of lower Ms (76 males and 39 females). The values were statistically analysed. RESULTS: The absolute size of the Prd increases significantly between M1 and M2/M3, whereas the relative size of this cusp increases significantly from M1 to M3. In the latter, reduction or disappearance of the cusps of the talonid is common. CONCLUSIONS: The results can be explained in the framework of the patterning cascade model. As the first cusp to appear developmentally, the Prd forms in response to signals from the primary enamel knot, likely contributing to its stability. Inhibitory signals emitted during the Prd formation may lead to the reduction or disappearance of the talonid cusps, if these do not have enough time to form before the end of the M morphogenetic process.

The Hidden Secrets of the Dental Calculus: Calibration of a Mass Spectrometry Protocol for Dental Calculus Protein Analysis.

Dental calculus is a solid deposit that forms and accumulates on the tooth surface, entrapping oral microorganisms, biomolecules, and other micro-debris found in the oral cavity. A mass spectrometry analysis of its protein content opens a vista into the subject's diet, oral flora, and even some aspects of health, thus providing new insight and expanding our knowledge of archaic cultures. Multiple experimental protocols have been proposed for the optimal extraction of proteins from dental calculus. Herein, we compared various experimental conditions in order to calibrate and validate a protocol for protein extraction. Our results show that a high concentration of acetic acid followed by mechanical crushing and sonication provided the highest protein yield, while acetone precipitation enabled the identification of more distinct proteins. We validated this protocol using archeological samples, identifying human and microbial proteins in specimens from the eighth and seventeenth centuries (approximately 250-1300 years ago). These findings demonstrate that the developed protocol is useful for studying excavated archaeological samples and that it might be utilized to explore the biohistory, dietary habits, and microbiome of archaic populations.

Testing the inhibitory cascade model in a recent human sample.

The Inhibitory Cascade Model was proposed by Kavanagh and colleagues (Nature, 449, 427-433 [2007]) after their experimental studies on the dental development of murine rodent species. These authors described an activator-inhibitor mechanism that has been employed to predict evolutionary size patterns of mammalian teeth, including hominins. In the present study, we measured the crown area of the three lower permanent molars (M1, M2, and M3) of a large recent modern human sample of male and female individuals from a collection preserved at the Institute of Anthropology of the University of Coimbra (Portugal). The main aim of the present study is to test if the size molar patterns observed in this human sample fits the Inhibitory Cascade Model. For this purpose, we first measured the crown area in those individuals preserving the complete molar series. Measurements were taken in photographs, using a planimeter and following well-tested techniques used in previous works. We then plot the M3 /M1 and M2 /M1  size ratios. Our results show that the premise of the Inhibitory Cascade Model, according to which the average of the crown area of M2 is approximately one-third of the sum of the crown area of the three molars, is fulfilled. However, our results also show that the individual values of a significant number of males and females are out of the 95% confidence interval predicted by the Inhibitory Cascade Model in rodents. As a result, the present analyses suggest that neither the sample of males, nor that of females, nor the pooled sample fits the Inhibitory Cascade Model. It is important to notice that, although this model has been successfully tested in a large number of current human populations, to the best of our knowledge this is the first study in which individual data have been obtained in a recent human population rather than using the average of the sample. Our results evince that, at the individual level, some factors not yet known could interfere with this model masking the modulation of the size on the molar series in modern humans. We suggest that the considerable delay in the onset of M3 formation in modern humans could be related to a weakening of the possible activation/inhibition process for this tooth. Finally, and in support of our conclusions, we have checked that the absolute and relative size of M1 and M2 is not related to the M3 agenesis in our sample. In line with other studies in primates, our results do not support the Inhibitory Cascade Model in a recent human sample. Further research is needed to better understand the genetic basis of this mechanism and its relationship to the phenotype. In this way, we may be able to find out which evolutionary changes may be responsible for the deviations observed in many species, including Homo sapiens.

In search of modern humans and the Early Upper Paleolithic at Manot Cave: An overview.

Manot Cave is a unique relict karst cave located in the western Galilee, north-western Israel. The cave was inhabited from the Late Middle Paleolithic through the Early Upper Paleolithic (EUP) periods until its main entrance collapsed, ca. 30 ka. The cave consists of an elongated main hall and two side chambers. The topography of the main hall consists of a steep talus inclining from the original entrance of the cave to the center, a plane area at the lowermost point of the main hall, and a smaller talus inclining from the eastern end of the cave. Nine field seasons (2010-2018) have been conducted so far at the cave. The excavations revealed dense accumulations of EUP deposits near the cave entrance (areas E and I), at the center (area D), at the base of the western talus (area C), and in the plane area (area A). This introductory article describes the cave and its characteristics and provides a background for various contributions in the special issue, devoted to Manot Cave.

The dental remains from the Early Upper Paleolithic of Manot Cave, Israel.

This study presents the dental remains discovered at Manot Cave (MC), Western Galilee, Israel. The cave contains evidence for human occupation during the Early Upper Paleolithic period (46-33 ka) mainly of Early Ahmarian (∼46-42 ka) and Levantine Aurignacian (∼38-34 ka) cultural levels. Six teeth (three deciduous and three permanent) were found at the site, of which four could be thoroughly analyzed. The morphology of the teeth was qualitatively described and analyzed using traditional and geometric morphometric methods. A large comparative sample was used in order to assess the morphological affiliation of the Manot specimens with other Homo groups. The results provided equivocal signals: the upper first premolar (MC-9 P3) is probably modern human; the upper deciduous second molar (MC-10 dm2) and the upper second permanent molar (MC-8 M2) might be modern humans; the lower second deciduous molar (MC-7 dm2) might be Neanderthal. Owing to the small sample size and the almost total lack of distinctive characteristics, our outcome could not supply conclusive evidence to address the question of whether Manot Aurignacian population came from Europe or descended from the local Ahmarian population.

Evidence of habitual behavior from non-alimentary dental wear on deciduous teeth from the Middle and Upper Paleolithic Cantabrian region, Northern Spain.

The use of 'teeth as tools' (non-masticatory or cultural-related dental wear) has largely been employed as a proxy for studying of past human behavior, mainly in permanent dentition from adult individuals. Here we present the analysis of the non-masticatory dental wear modifications on the deciduous dentition assigned to eight Neanderthal and anatomically modern human subadult individuals from Mousterian to Magdalenian technocultural contexts in the Cantabrian region (Northern Spain). Although preliminary, we tentatively suggest that these eight subadults present activity-related dental wear, including cultural striations, chipped enamel, toothpick grooves, and subvertical grooves. We also found evidence of habitual dental hygienic practices in the form of toothpicking on a deciduous premolar. Orientation of the cultural striations indicates similar handedness development as in modern children. Taken together, these dental wear patterns support the participation of young individuals in group activities, making them potential contributors to group welfare. This study potentially adds new evidence to the importance of the use of the mouth in paramasticatory activities or as a third hand throughout the Pleistocene, which can be confirmed with a more specific reference sample.

When did Homo sapiens first reach Southeast Asia and Sahul?

Anatomically modern humans (Homo sapiens, AMH) began spreading across Eurasia from Africa and adjacent Southwest Asia about 50,000-55,000 years ago (ca 50-55 ka). Some have argued that human genetic, fossil, and archaeological data indicate one or more prior dispersals, possibly as early as 120 ka. A recently reported age estimate of 65 ka for Madjedbebe, an archaeological site in northern Sahul (Pleistocene Australia-New Guinea), if correct, offers what might be the strongest support yet presented for a pre-55-ka African AMH exodus. We review evidence for AMH arrival on an arc spanning South China through Sahul and then evaluate data from Madjedbebe. We find that an age estimate of >50 ka for this site is unlikely to be valid. While AMH may have moved far beyond Africa well before 50-55 ka, data from the region of interest offered in support of this idea are not compelling.

Modern human changes in regulatory regions implicated in cortical development.

BACKGROUND: Recent paleogenomic studies have highlighted a very small set of proteins carrying modern human-specific missense changes in comparison to our closest extinct relatives. Despite being frequently alluded to as highly relevant, species-specific differences in regulatory regions remain understudied. Here, we integrate data from paleogenomics, chromatin modification and physical interaction, and single-cell gene expression of neural progenitor cells to identify derived regulatory changes in the modern human lineage in comparison to Neanderthals/Denisovans. We report a set of genes whose enhancers and/or promoters harbor modern human single nucleotide changes and are active at early stages of cortical development. RESULTS: We identified 212 genes controlled by regulatory regions harboring modern human changes where Neanderthals/Denisovans carry the ancestral allele. These regulatory regions significantly overlap with putative modern human positively-selected regions and schizophrenia-related genetic loci. Among the 212 genes, we identified a substantial proportion of genes related to transcriptional regulation and, specifically, an enrichment for the SETD1A histone methyltransferase complex, known to regulate WNT signaling for the generation and proliferation of intermediate progenitor cells. CONCLUSIONS: This study complements previous research focused on protein-coding changes distinguishing our species from Neanderthals/Denisovans and highlights chromatin regulation as a functional category so far overlooked in modern human evolution studies. We present a set of candidates that will help to illuminate the investigation of modern human-specific ontogenetic trajectories.

Climate variability in early expansions of Homo sapiens in light of the new record of micromammals in Misliya Cave, Israel.

In this study, we provide the first taphonomic and taxonomic descriptions of the micromammals from Misliya Cave, where recently a Homo sapiens hemimaxilla has been reported. This finding significantly extends the time frame for the out-of-Africa presence of anatomically modern humans. It also provides an opportunity to reassess variation in early modern human population responses to climate change in the Levantine sequence. Information on species ranking and diversity estimations (Shannon functions) is obtained from quantitative data across 31 Levantine assemblages and investigated in a broad comparative frame using multivariate analyses. Recent models of human-climate interactions in the late Early-Middle Paleolithic of the southern Levant have drawn heavily on on-site associations of human fossils with remains of micromammals. However, there has been little, if any, attempt to examine the long-term picture of how paleocommunities of micromammals responded qualitatively and quantitatively to climatic oscillations of the region by altering their compositional complexity. Consequently, our understanding is vastly limited in regard to the paleoecosystem functions that linked past precipitation shifts to changes in primary producers and consumers or as to the background climatic conditions that allowed for the development of highly nonanalog ancient communities in the region. Although previous studies argued for a correspondence between alternations in H. sapiens and Neanderthal occupations of the Levant and faunal shifts in key biostratigraphic indicator taxa (such as Euro-Siberian Ellobius versus Saharo-Arabian Mastomys and Arvicanthis), our data indicate the likelihood that early H. sapiens populations (Misliya and Qafzeh hominins) persisted through high amplitudes of paleoecological and climatic oscillations. It is unlikely, given these results, that climate functioned as a significant filter of early modern human persistence and genetic interactions with Neanderthals in the Levant.

A refined chronology for the Gravettian sequence of Abri Pataud.

Abri Pataud (France) is the type site in studies focusing on the appearance of modern humans and the development of classic Upper Paleolithic technocomplexes in Europe. It contains important evidence of successful adaptation strategies of modern humans to new territories and in response to sharply changing climatic conditions that characterized Marine Isotope Stages 3 and 2. Despite being for decades one of the best excavated and most studied Paleolithic sites, the chronology of Abri Pataud has lacked precision and revealed large discrepancies. The chronology of the lowermost part of the sequence (Levels 14-5) was refined in 2011 with the publication of 32 new radiocarbon determinations, mainly from the Aurignacian levels. In contrast, the Gravettian levels (Levels 5-2) remained poorly dated until now. Here, we present 18 new radiocarbon dates on cut-marked animal bones from the Gravettian part of the site, which complete the dating of this important sequence. The determinations are analyzed using Bayesian statistical modeling, and the results allow us to place the start of the Gravettian at the site between ∼33,000 and 32,000 cal BP (∼29,000-28,000 BP). We discuss the succession of the Gravettian facies across the sequence (Bayacian, Noaillian, Rayssian), as well as the likely duration of each archaeological level. With a total of more than 50 radiocarbon determinations, Abri Pataud offers secure information for the appearance and development of the technocomplexes linked with early modern humans and their establishment in western Europe. Based on published genetic data, it appears that it is the Gravettian hunter-gatherers and subsequent human groups, rather than the earlier Aurignacian and pre-Aurignacian groups, that contributed to the genetic signature of later and living Europeans. Hence, elucidating the precise timing of the Gravettian appearance has broad implications in our understanding of late human evolution across Europe.

Enamel thickness and growth rates in modern human permanent first molars over a 2000 year period in Britain.

OBJECTIVES: This study explores variation and trends in first molar enamel thickness and daily enamel secretion rates over a 2000 year period in Britain. METHODS: Permanent first molars (n = 89) from the Roman, Anglo-Saxon, and Medieval periods, as well as modern-day Britain, were analyzed using standard histological methods. Relative enamel thickness (RET) and linear measurements of cuspal and lateral thickness were calculated for mesial cusps. Daily secretion rates (DSRs) were calculated for inner, mid, and outer enamel regions in both cuspal and lateral enamel. Significant differences and trends were identified between samples using nonparametric statistical tests. RESULTS: Enamel thickness differed between some populations, but no temporal trends were identified. Early Anglo-Saxon molars had significantly thinner RET than both Late Anglo-Saxon (p < .00) and Medieval (p < .00) molars. Lateral enamel from the Roman molars was significantly thinner than the modern-day sample (p = .04). In contrast, a significant slowing trend in DSRs was observed across the more ancient to modern-day samples in every measured region except the mid-lateral enamel region. DISCUSSION: This study presents the first evidence for a gradual slowing in the daily rate that enamel is secreted in molars over the past 2000 years in Britain. However, this trend was not matched by consistent or significant positive or negative shifts in enamel thickness. These findings suggest that modern human molars of similar enamel thickness, from different modern and ancient populations, formed at different rates.

Comparing fitness and drift explanations of Neanderthal replacement.

There is a general consensus among archaeologists that replacement of Neanderthals by anatomically modern humans in Europe occurred around 40-35 ka. However, the causal mechanism for this replacement continues to be debated. Proposed models have featured either fitness advantages in favour of anatomically modern humans or invoked neutral drift under various preconditions. Searching for specific fitness advantages in the archaeological record has proven difficult, as these may be obscured, absent or subject to interpretation. To bridge this gap, we rigorously compare the system-level properties of fitness- and drift-based explanations of Neanderthal replacement. Our stochastic simulations and analytical predictions show that, although both fitness and drift can produce replacement, they present important differences in (i) required initial conditions, (ii) reliability, (iii) time to replacement, and (iv) path to replacement (population histories). These results present useful opportunities for comparison with archaeological and genetic data. We find greater agreement between the available empirical evidence and the system-level properties of replacement by differential fitness, rather than by neutral drift.