Scurvy in the tropics: Evidence for increasing non-adult micronutrient deficiency with the transition to agriculture in northern Vietnam

Objective

Scurvy in non-adults was assessed at the Pre-Neolithic site of Con Co Ngua and the Neolithic site of Man Bac in northern Vietnam to investigate nutritional stress during the agricultural transition in Mainland Southeast Asia (MSEA).

Materials

One hundred and four human skeletons under the age of 20 years old were assessed.

Methods

Lesions were recorded macroscopically and radiographically. Differential diagnosis using prior established paleopathological diagnostic criteria for scurvy was conducted.

Results

There was no clear evidence for scurvy at Con Co Ngua and a high burden of scurvy was present at Man Bac (>79% diagnosed with probable scurvy). Scurvy levels were high across all non-adult ages at Man Bac indicating significant burden throughout childhood and adolescence.

Conclusions

No scurvy at Con Co Ngua is consistent with widely available food sources at the peak of the Holocene thermal maximum. High levels of scurvy at Man Bac corresponds with decreased dietary diversity, high pathogen load, and increased population stress with the transition to agriculture around the time of the 4.2 ka desertification event.

Significance

This is the first systematic population-level non-adult investigation of specific nutritional disease in MSEA and demonstrates an increase in nutritional stress during the Neolithic transition in northern Vietnam.

Limitations

Subperiosteal new bone deposits can be due to normal growth in infants and young children, therefore, identification of scurvy in children under the age of 4 years needs to be considered critically.

Suggestions for Further Research

Further work in diagnosing specific nutritional disease in other non-adult cohorts throughout MSEA is required.     

Craniometric Data Supports Demic Diffusion Model for the Spread of Agriculture into Europe

Background

The spread of agriculture into Europe and the ancestry of the first European farmers have been subjects of debate and controversy among geneticists, archaeologists, linguists and anthropologists. Debates have centred on the extent to which the transition was associated with the active migration of people as opposed to the diffusion of cultural practices. Recent studies have shown that patterns of human cranial shape variation can be employed as a reliable proxy for the neutral genetic relationships of human populations.

Methodology/Principal Findings

Here, we employ measurements of Mesolithic (hunter-gatherers) and Neolithic (farmers) crania from Southwest Asia and Europe to test several alternative population dispersal and hunter-farmer gene-flow models. We base our alternative hypothetical models on a null evolutionary model of isolation-by-geographic and temporal distance. Partial Mantel tests were used to assess the congruence between craniometric distance and each of the geographic model matrices, while controlling for temporal distance. Our results demonstrate that the craniometric data fit a model of continuous dispersal of people (and their genes) from Southwest Asia to Europe significantly better than a null model of cultural diffusion.

Conclusions/Significance

Therefore, this study does not support the assertion that farming in Europe solely involved the adoption of technologies and ideas from Southwest Asia by indigenous Mesolithic hunter-gatherers. Moreover, the results highlight the utility of craniometric data for assessing patterns of past population dispersal and gene flow.     

Phylogeographic history of mitochondrial haplogroup J in Scandinavia

Background

Mitochondrial DNA haplogroup J is the third most frequent haplogroup in modern-day Scandinavia, although it did not originate there. To infer the genetic history of haplogroup J in Scandinavia, we examined worldwide mitogenome sequences using a maximum-likelihood phylogenetic approach.

Methods

Haplogroup J mitogenome sequences were gathered from GenBank (n = 2245) and aligned against the ancestral Reconstructed Sapiens Reference Sequence. We also analyzed haplogroup J Viking Age sequences from the European Nucleotide Archive (n = 54). Genetic distances were estimated from these data and projected onto a maximum likelihood rooted phylogenetic tree to analyze clustering and branching dates.

Results

Haplogroup J originated approximately 42.6 kya (95% CI: 30.0–64.7), with several of its earliest branches being found within the Arabian Peninsula and Northern Africa. J1b was found most frequently in the Near East and Arabian Peninsula, while J1c occurred most frequently in Europe. Based on phylogenetic dating, subhaplogroup J1c has its early roots in the Mediterranean and Western Balkans. Otherwise, the majority of the branches found in Scandinavia are younger than those seen elsewhere, indicating that haplogroup J dispersed relatively recently into Northern Europe, most plausibly with Neolithic farmers.

Conclusions

Haplogroup J appeared when Scandinavia was transitioning to agriculture over 6 kya, with J1c being the most common lineage there today. Changes in the distribution of haplogroup J mtDNAs were likely driven by the expansion of farming from West Asia into Southern Europe, followed by a later expansion into Scandinavia, with other J subhaplogroups appearing among Scandinavian groups as early as the Viking Age.

     

A statistical model for mapping morphological shape

Background  

Living things come in all shapes and sizes, from bacteria, plants, and animals to humans. Knowledge about the genetic mechanisms for biological shape has far-reaching implications for a range spectrum of scientific disciplines including anthropology, agriculture, developmental biology, evolution and biomedicine.     

Y-SNPs do not indicate hybridisation between European aurochs and domestic cattle

Background

Previous genetic studies of modern and ancient mitochondrial DNA have confirmed the Near Eastern origin of early European domestic cattle. However, these studies were not able to test whether hybridisation with male aurochs occurred post-domestication. To address this issue, Götherström and colleagues (2005) investigated the frequencies of two Y-chromosomal haplotypes in extant bulls. They found a significant influence of wild aurochs males on domestic populations thus challenging the common view on early domestication and Neolithic stock-rearing. To test their hypothesis, we applied these Y-markers on Neolithic bone specimens from various European archaeological sites.

Methods and Findings

Here, we have analysed the ancient DNA of 59 Neolithic skeletal samples. After initial molecular sexing, two segregating Y-SNPs were identified in 13 bulls. Strikingly, our results do not support the hypothesis that these markers distinguish European aurochs from domesticated cattle.

Conclusions

The model of a rapid introduction of domestic cattle into Central Europe without significant crossbreeding with local wild cattle remains unchallenged.     

New evidence for Neolithic rice cultivation and Holocene environmental change in the Fuzhou Basin,southeast China

A stratified profile of the Zhuangbianshan (ZBS) archaeological site (Fuzhou Basin, Fujian) was studied to investigate Neolithic era anthropogenic influence and associated environmental changes. Analysis of the archaeological sediments focused on phytoliths, palynomorphs and microcharcoal. Until now, a lack of direct evidence for agriculture has made it difficult to know if Neolithic cultures of this area relied on the exploitation of wild plants such as nuts and sago palm, or a combination of farming and foraging. Three types of rice phytoliths were found in ZBS archaeological deposits, providing robust evidence for rice farming as part of a broad-spectrum Neolithic subsistence economy centered on fishing and hunting. Chronologies based on AMS ¹⁴C dates and artifact typology place the earliest rice during the Tanshishan (TSS) Period (5,000–4,300 cal bp) followed by a shift to economic dependency on rice in the Huangguashan (HGS) Period (4,300–3,500 cal bp). The ZBS phytolith assemblage contains high frequencies of rice husk (peaked-shape glume cells) phytoliths, with far fewer leaf and stem types. This indicates late stage processing activities such as dehusking, implying a focus on consumption rather than rice production. High concentrations of charcoal in the Neolithic ZBS deposits indicate local human settlement and peaks in fire use. The ZBS pollen record also reflects human settlement and peaks in local forest clearance during the Neolithic. Forest cover was renewed when the site was temporarily abandoned following the Neolithic. Rapid formation of the Min River floodplain began ~2,000 cal bp in association with retreating sea level and intensifying anthropogenic influence. Prior to that, rice farming in the Fuzhou Basin was limited by the scarcity of wetlands suitable for agriculture.     

High frequency of lactose intolerance in a prehistoric hunter-gatherer population in northern Europe

Background  

Genes and culture are believed to interact, but it has been difficult to find direct evidence for the process. One candidate example that has been put forward is lactase persistence in adulthood, i.e. the ability to continue digesting the milk sugar lactose after childhood, facilitating the consumption of raw milk. This genetic trait is believed to have evolved within a short time period and to be related with the emergence of sedentary agriculture.     

Uniparental Markers of Contemporary Italian Population Reveals Details on Its Pre-Roman Heritage

Background

According to archaeological records and historical documentation, Italy has been a melting point for populations of different geographical and ethnic matrices. Although Italy has been a favorite subject for numerous population genetic studies, genetic patterns have never been analyzed comprehensively, including uniparental and autosomal markers throughout the country.

Methods/Principal Findings

A total of 583 individuals were sampled from across the Italian Peninsula, from ten distant (if homogeneous by language) ethnic communities — and from two linguistic isolates (Ladins, Grecani Salentini). All samples were first typed for the mitochondrial DNA (mtDNA) control region and selected coding region SNPs (mtSNPs). This data was pooled for analysis with 3,778 mtDNA control-region profiles collected from the literature. Secondly, a set of Y-chromosome SNPs and STRs were also analyzed in 479 individuals together with a panel of autosomal ancestry informative markers (AIMs) from 441 samples. The resulting genetic record reveals clines of genetic frequencies laid according to the latitude slant along continental Italy – probably generated by demographical events dating back to the Neolithic. The Ladins showed distinctive, if more recent structure. The Neolithic contribution was estimated for the Y-chromosome as 14.5% and for mtDNA as 10.5%. Y-chromosome data showed larger differentiation between North, Center and South than mtDNA. AIMs detected a minor sub-Saharan component; this is however higher than for other European non-Mediterranean populations. The same signal of sub-Saharan heritage was also evident in uniparental markers.

Conclusions/Significance

Italy shows patterns of molecular variation mirroring other European countries, although some heterogeneity exists based on different analysis and molecular markers. From North to South, Italy shows clinal patterns that were most likely modulated during Neolithic times.     

A hierarchical Bayesian network approach for linkage disequilibrium modeling and data-dimensionality reduction prior to genome-wide association studies

Background  

Discovering the genetic basis of common genetic diseases in the human genome represents a public health issue. However, the dimensionality of the genetic data (up to 1 million genetic markers) and its complexity make the statistical analysis a challenging task.     

Molecular mechanistic associations of human diseases

Background  

The study of relationships between human diseases provides new possibilities for biomedical research. Recent achievements on human genetic diseases have stimulated interest to derive methods to identify disease associations in order to gain further insight into the network of human diseases and to predict disease genes.     

DNA indels in coding regions reveal selective constraints on protein evolution in the human lineage

Background  

Insertions and deletions of DNA segments (indels) are together with substitutions the major mutational processes that generate genetic variation. Here we focus on recent DNA insertions and deletions in protein coding regions of the human genome to investigate selective constraints on indels in protein evolution.     

Genetic diversity in India and the inference of Eurasian population expansion

Background  

Genetic studies of populations from the Indian subcontinent are of great interest because of India's large population size, complex demographic history, and unique social structure. Despite recent large-scale efforts in discovering human genetic variation, India's vast reservoir of genetic diversity remains largely unexplored.     

Investigating past range dynamics for a weed of cultivation,Silene vulgaris

Since the last glacial maximum (LGM), many plant and animal taxa have expanded their ranges by migration from glacial refugia. Weeds of cultivation may have followed this trend or spread globally following the expansion of agriculture or ruderal habitats associated with human‐mediated disturbance. We tested whether the range expansion of the weed Silene vulgaris across Europe fit the classical model of postglacial expansion from southern refugia, or followed known routes of the expansion of human agricultural practices. We used species distribution modeling to predict spatial patterns of postglacial expansion and contrasted these with the patterns of human agricultural expansion. A population genetic analysis using microsatellite loci was then used to test which scenario was better supported by spatial patterns of genetic diversity and structure. Genetic diversity was highest in southern Europe and declined with increasing latitude. Locations of ancestral demes from genetic cluster analysis were consistent with areas of predicted refugia. Species distribution models showed the most suitable habitat in the LGM on the southern coasts of Europe. These results support the typical postglacial northward colonization from southern refugia while refuting the east‐to‐west agricultural spread as the main mode of expansion for S. vulgaris. We know that S. vulgaris has recently colonized many regions (including North America and other continents) through human‐mediated dispersal, but there is no evidence for a direct link between the Neolithic expansion of agriculture and current patterns of genetic diversity of S. vulgaris in Europe. Therefore, the history of range expansion of S. vulgaris likely began with postglacial expansion after the LGM, followed by more recent global dispersal by humans.     

GAPscreener: An automatic tool for screening human genetic association literature in PubMed using the support vector machine technique

Background  

Synthesis of data from published human genetic association studies is a critical step in the translation of human genome discoveries into health applications. Although genetic association studies account for a substantial proportion of the abstracts in PubMed, identifying them with standard queries is not always accurate or efficient. Further automating the literature-screening process can reduce the burden of a labor-intensive and time-consuming traditional literature search. The Support Vector Machine (SVM), a well-established machine learning technique, has been successful in classifying text, including biomedical literature. The GAPscreener, a free SVM-based software tool, can be used to assist in screening PubMed abstracts for human genetic association studies.     

Diet-induced obesity in zebrafish shares common pathophysiological pathways with mammalian obesity

Background  

Obesity is a multifactorial disorder influenced by genetic and environmental factors. Animal models of obesity are required to help us understand the signaling pathways underlying this condition. Zebrafish possess many structural and functional similarities with humans and have been used to model various human diseases, including a genetic model of obesity. The purpose of this study was to establish a zebrafish model of diet-induced obesity (DIO).     

Domain duplication, divergence, and loss events in vertebrate Msx paralogs reveal phylogenomically informed disease markers

Background  

Msx originated early in animal evolution and is implicated in human genetic disorders. To reconstruct the functional evolution of Msx and inform the study of human mutations, we analyzed the phylogeny and synteny of 46 metazoan Msx proteins and tracked the duplication, diversification and loss of conserved motifs.     

Deficiency of Pten accelerates mammary oncogenesis in MMTV-Wnt-1 transgenic mice

Background  

Germline mutations in the tumor suppressor PTEN predispose human beings to breast cancer, and genetic and epigenetic alterations of PTEN are also detected in sporadic human breast cancer. Germline Pten mutations in mice lead to the development of a variety of tumors, but mammary carcinomas are infrequently found, especially in mice under the age of six months.     

Genetic characterization of the ABO blood group in Neandertals

Background  

The high polymorphism rate in the human ABO blood group gene seems to be related to susceptibility to different pathogens. It has been estimated that all genetic variation underlying the human ABO alleles appeared along the human lineage, after the divergence from the chimpanzee lineage. A paleogenetic analysis of the ABO blood group gene in Neandertals allows us to directly test for the presence of the ABO alleles in these extinct humans.     

Therapeutic potential of antisense oligodeoxynucleotides in downregulating p53 oncogenic mutations in cancers

Purpose of work  

Mutation of the p53 gene is the most common genetic alteration in human cancers. Our study proposes to rationally design a p53 antisense oligonucleotide (ASO) repository, which contains a series of ASOs containing single nucleotide differences to discriminate between each mutant and wild type (WT) p53.