Modern Human DNA Research Articles

Infectious disease in the Pleistocene: Old friends or old foes?

The impact of endemic and epidemic disease on humans has traditionally been seen as a comparatively recent historical phenomenon associated with the Neolithisation of human groups, an increase in population size led by sedentarism, and increasing contact with domesticated animals as well as species occupying opportunistic symbiotic and ectosymbiotic relationships with humans. The orthodox approach is that Neolithisation created the conditions for increasing population size able to support a reservoir of infectious disease sufficient to act as selective pressure. This orthodoxy is the result of an overly simplistic reliance on skeletal data assuming that no skeletal lesions equated to a healthy individual, underpinned by the assumption that hunter-gatherer groups were inherently healthy while agricultural groups acted as infectious disease reservoirs. The work of van Blerkom, Am. J. Phys. Anthropol., vol. suppl 37 (2003), Wolfe et al., Nature, vol. 447 (2007) and Houldcroft and Underdown, Am. J. Phys. Anthropol., vol. 160, (2016) has changed this landscape by arguing that humans and pathogens have long been fellow travelers. The package of infectious diseases experienced by our ancient ancestors may not be as dissimilar to modern infectious diseases as was once believed. The importance of DNA, from ancient and modern sources, to the study of the antiquity of infectious disease, and its role as a selective pressure cannot be overstated. Here we consider evidence of ancient epidemic and endemic infectious diseases with inferences from modern and ancient human and hominin DNA, and from circulating and extinct pathogen genomes. We argue that the pandemics of the past are a vital tool to unlock the weapons needed to fight pandemics of the future.

Coronaviruses caused epidemics for millennia

Inside modern human DNA lie traces of ancient coronavirus infections from many, many years ago ( Curr. Biol. 2021, DOI: 10.1016/j.cub.2021.05.067 ). Around 25,000 years ago, in fact. That’s the conclusion of a team of researchers led by David Enard of the University of Arizona. The scientists used a large database of individual human genomes known as 1000 Genomes to compare the genes coding for proteins that interact with coronaviruses, including SARS-CoV-2. They found evidence in the DNA of people whose families came from East Asia that a coronavirus epidemic raged in that region around 25,000 years ago. In addition, the virus had changed the DNA of the survivors and their descendants. After completing the computational genomic analysis, the researchers synthesized human and coronavirus proteins and confirmed that they interact, as suggested by the team’s earlier results. The researchers also identified previously unknown drug targets that they say could be

Modern human DNA analyses with special reference to the inner dual-structure model of Yaponesian

Modern human DNA analyses with special reference to the inner dual-structure model of Yaponesian

Inferring the model and onset of natural selection under varying population size from the site frequency spectrum and haplotype structure.

A fundamental question about adaptation in a population is the time of onset of the selective pressure acting on beneficial alleles. Inferring this time, in turn, depends on the selection model. We develop a framework of approximate Bayesian computation (ABC) that enables the use of the full site frequency spectrum and haplotype structure to test the goodness-of-fit of selection models and estimate the timing of selection under varying population size scenarios. We show that our method has sufficient power to distinguish natural selection from neutrality even if relatively old selection increased the frequency of a pre-existing allele from 20% to 50% or from 40% to 80%. Our ABC can accurately estimate the time of onset of selection on a new mutation. However, estimates are prone to bias under the standing variation model, possibly due to the uncertainty in the allele frequency at the onset of selection. We further extend our approach to take advantage of ancient DNA data that provides information on the allele frequency path of the beneficial allele. Applying our ABC, including both modern and ancient human DNA data, to four pigmentation alleles in Europeans, we detected selection on standing variants that occurred after the dispersal from Africa even though models of selection on a new mutation were initially supported for two of these alleles without the ancient data.

Palaeoproteomics for human evolution studies

The commonplace sequencing of Neanderthal, Denisovan and ancient modern human DNA continues to revolutionize our understanding of hominin phylogeny and interaction(s). The challenge with older fossils is that the progressive fragmentation of DNA even under optimal conditions, a function of time and temperature, results in ever shorter fragments of DNA. This process continues until no DNA can be sequenced or reliably aligned. Ancient proteins ultimately suffer a similar fate, but are a potential alternative source of biomolecular sequence data to investigate hominin phylogeny given their slower rate of fragmentation. In addition, ancient proteins have been proposed to potentially provide insights into in vivo biological processes and can be used to provide additional ecological information through large scale ZooMS (Zooarchaeology by Mass Spectrometry) screening of unidentifiable bone fragments. However, as initially with ancient DNA, most ancient protein research has focused on Late Pleistocene or Holocene samples from Europe. In addition, only a limited number of studies on hominin remains have been published. Here, an updated review on ancient protein analysis in human evolutionary contexts is given, including the identification of specific knowledge gaps and existing analytical limits, as well as potential avenues to overcome these.

Histoire de l’utilisation des laitages et de la persistance du gène de la lactase

This chapter covers archaeological and biological studies that have been insightful in the understanding of dairying history and the evolution of lactase persistence in humans. More specifically, we report results from lipid residue analyses on archaeological pottery vessels, ancient and modern human DNA and explain the biology and genetics of lactase persistence. Available data suggests that domesticated animals were used for milk consumption by humans early in the Neolithic, while contemporaneous populations seem to have been mainly lactose intolerant. This contrasts with modern European populations, which show a generally high proportion of lactase persistence.

Neanderthal-Derived Genetic Variation Shapes Modern Human Cranium and Brain

Before their disappearance from the fossil record approximately 40,000 years ago, Neanderthals, the ancient hominin lineage most closely related to modern humans, interbred with ancestors of present-day humans. The legacy of this gene flow persists through Neanderthal-derived variants that survive in modern human DNA; however, the neural implications of this inheritance are uncertain. Here, using MRI in a large cohort of healthy individuals of European-descent, we show that the amount of Neanderthal-originating polymorphism carried in living humans is related to cranial and brain morphology. First, as a validation of our approach, we demonstrate that a greater load of Neanderthal-derived genetic variants (higher “NeanderScore”) is associated with skull shapes resembling those of known Neanderthal cranial remains, particularly in occipital and parietal bones. Next, we demonstrate convergent NeanderScore-related findings in the brain (measured by gray- and white-matter volume, sulcal depth, and gyrification index) that localize to the visual cortex and intraparietal sulcus. This work provides insights into ancestral human neurobiology and suggests that Neanderthal-derived genetic variation is neurologically functional in the contemporary population.

A comprehensive exploration of Java man: bio-cultural evolution from Homo Erectus to Homo Sapiens

ABSTRACT An overlap of time period between Homo erectus and Homo sapiens has not been confirmed. In the history of man, there have been two missing links: one between man and ape, and one between progressive Homo erectus and archaic Homo sapiens . Specimen dating on Java Man has been discrepant among research groups, and the use of molecular biology in ancient specimens has been a novelty. This study intends to use fossilised specimens, to harvest DNA to be sequenced for ribosomal DNA analysis for comparative phylogeny among ancient and modern man and other hominids. Dental calculus will be analysed to identify starch, carbohydrate, and protein to illustrate paleo dietary pattern. Soil samples will be examined for pollen and phytoliths to elaborate on ancient ecosystem. Blood samples will be procured from indigenous people along the riverflow region of Bengawan Solo to analyse modern human DNA. We hope that we may reconstruct the evolution pathway, construct the phylogenetic tree between ancient and modern hominids, and discover the uniqueness of Homo sapiens sapiens . Keywords: Java Man, Ribosomal DNA, Hominid Phylogenetic,

Paleomicrobiology Data: Authentification and Interpretation.

The authenticity of some of the very first works in the field of paleopathology has been questioned, and standards have been progressively established for the experiments and the interpretation of data. Whereas most problems initially arose from the contamination of ancient specimens with modern human DNA, the situation is different in the field of paleomicrobiology, in which the risk for contamination is well-known and adequately managed by any laboratory team with expertise in the routine diagnosis of modern-day infections. Indeed, the exploration of ancient microbiota and pathogens is best done by such laboratory teams, with research directed toward the discovery and implementation of new techniques and the interpretation of data.

Reducing microbial and human contamination in DNA extractions from ancient bones and teeth.

Although great progress has been made in improving methods for generating DNA sequences from ancient biological samples, many, if not most, samples are still not amenable for analyses due to overwhelming contamination with microbial or modern human DNA. Here we explore different DNA decontamination procedures for ancient bones and teeth for use prior to DNA library preparation and high-throughput sequencing. Two procedures showed promising results: (i) the release of surface-bound DNA by phosphate buffer and (ii) the removal of DNA contamination by sodium hypochlorite treatment. Exposure to phosphate removes on average 64% of the microbial DNA from bone powder but only 37% of the endogenous DNA (from the organism under study), increasing the percentage of informative sequences by a factor of two on average. An average 4.6-fold increase, in one case reaching 24-fold, is achieved by sodium hypochlorite treatment, albeit at the expense of destroying 63% of the endogenous DNA preserved in the bone. While both pretreatment methods described here greatly reduce the cost of genome sequencing from ancient material due to efficient depletion of microbial DNA, we find that the removal of human DNA contamination remains a challenging problem.

Re-inventing ancient human DNA.

For a long time, the analysis of ancient human DNA represented one of the most controversial disciplines in an already controversial field of research. Scepticism in this field was only matched by the long-lasting controversy over the authenticity of ancient pathogen DNA. This ambiguous view on ancient human DNA had a dichotomous root. On the one hand, the interest in ancient human DNA is great because such studies touch on the history and evolution of our own species. On the other hand, because these studies are dealing with samples from our own species, results are easily compromised by contamination of the experiments with modern human DNA, which is ubiquitous in the environment. Consequently, some of the most disputed studies published - apart maybe from early reports on million year old dinosaur or amber DNA - reported DNA analyses from human subfossil remains. However, the development of so-called next- or second-generation sequencing (SGS) in 2005 and the technological advances associated with it have generated new confidence in the genetic study of ancient human remains. The ability to sequence shorter DNA fragments than with PCR amplification coupled to traditional Sanger sequencing, along with very high sequencing throughput have both reduced the risk of sequencing modern contamination and provided tools to evaluate the authenticity of DNA sequence data. The field is now rapidly developing, providing unprecedented insights into the evolution of our own species and past human population dynamics as well as the evolution and history of human pathogens and epidemics. Here, we review how recent technological improvements have rapidly transformed ancient human DNA research from a highly controversial subject to a central component of modern anthropological research. We also discuss potential future directions of ancient human DNA research.

Epigenetic plasticity following early stress predicts long-term health outcomes in rhesus macaques.

Early life stress has been linked with poorer lifelong health outcomes across species, including modern and ancient humans. Epigenetic mechanisms, such as DNA methylation patterning of stress pathway genes in stress-responsive tissue, may play an important role in the long-term health effects of early stress across species. The relationships among early maternal care quality, DNA methylation patterns in a candidate stress pathway gene (serotonin transporter, 5-HTT) linked region in blood DNA, and adult health outcomes were examined in male and female rhesus macaques, excellent models of human health. Male (n = 12) and female (n = 32) infants were observed with their mothers for the first 12 weeks of life and 5-HTT linked DNA methylation was measured in blood at 12 weeks of age. Approximately 8 years later, health-related measures were collected for the 25 animals (6 male and 19 female) that were available for study. Health composite scores were generated using factor analysis of body condition, body weight, and diagnosis of diarrhea during the lifespan. Better quality maternal care predicted lower 5-HTT linked methylation at 12 weeks of age. Lower 5-HTT methylation, in turn, predicted better health composite scores in adulthood, including better body condition, greater body weight and absence of lifetime diarrhea. These data suggest that the epigenetic regulation of 5-HTT may be one biomarker of the link between early stress and lifetime health trajectories. Future studies will examine whether epigenetic signatures in modern and ancient human DNA lends insight into stress and health and natural selection in human evolutionary history.

A Brief Overview of the Last 10 Years of Major Late Pleistocene Discoveries in the Old World: Homo floresiensis, Neanderthal, and Denisovan

In the last ten years, new fossil, archaeological, and genetic data have significantly altered our understanding of the peopling of the Old World in the Late Pleistocene. Scholars have long been challenged to define humanity’s place in evolution and to trace our phylogeny. Differences in the skeletal morphology of hominin fossils have often led to the naming of distinct new species, but recent genetic findings have challenged the traditional perspective by demonstrating that modern human DNA contains genes inherited from Neanderthals and Denisovans, thus questioning their status as separate species. The recent discovery of Homo floresiensis from Flores Island has also raised interesting queries about how much genetic and morphological diversity was present during the Late Pleistocene. This paper discusses the nature and implications of the evidence with respect to Homo floresiensis, Neanderthals, and Denisovans and briefly reviews major Late Pleistocene discoveries from the last ten years of research in the Old World and their significance to the study of human evolution.

Faunal record identifies Bering isthmus conditions as constraint to end-Pleistocene migration to the New World.

Human colonization of the New World is generally believed to have entailed migrations from Siberia across the Bering isthmus. However, the limited archaeological record of these migrations means that details of the timing, cause and rate remain cryptic. Here, we have used a combination of ancient DNA, 14C dating, hydrogen and oxygen isotopes, and collagen sequencing to explore the colonization history of one of the few other large mammals to have successfully migrated into the Americas at this time: the North American elk (Cervus elaphus canadensis), also known as wapiti. We identify a long-term occupation of northeast Siberia, far beyond the species's current Old World distribution. Migration into North America occurred at the end of the last glaciation, while the northeast Siberian source population became extinct only within the last 500 years. This finding is congruent with a similar proposed delay in human colonization, inferred from modern human mitochondrial DNA, and suggestions that the Bering isthmus was not traversable during parts of the Late Pleistocene. Our data imply a fundamental constraint in crossing Beringia, placing limits on the age and mode of human settlement in the Americas, and further establish the utility of ancient DNA in palaeontological investigations of species histories.

The truth is out there

The truth is out there

Les Néandertaliens d’El Sidrón (Asturies, Espagne). Actualisation d’un nouvel échantillon

This paper synthesizes and updates the information coming from the El Sidrón (Asturias, Northern Spain) neandertal site. Since 2000, a new sample of Homo neanderthalensis dated to at least 49,000years old is being systematically recovered at the El Sidrón cave site. The bone assemblage is located in a secondary position, and certainly derives from a close location. The sample is almost exclusively composed of human remains. There is a moderate number of Middle Paleolithic stone tools (n≈415) and very few macro-faunal remains. All skeletal parts are preserved, including some rare bones such as the hyoid bone. Teeth are abundant (n=213), cranial and postcranial remains are also well represented, but fragmentary, with a special presence of foot and hand bones. A minimum number of thirteen individuals has been identified, comprising different developmental stages from infancy to adulthood: one infant, two juveniles, three adolescents, and seven adults. Paleobiology of the El Sidrón humans fits the pattern found in other neandertal samples: a high incidence of dental hypoplasia and interproximal grooves, yet no serious traumatic lesions are present. Moreover, unambiguous evidence of human-induced modifications (cannibalism) was found on the human remains: cut marks, percussion pitting, conchoidal scars and adhering flakes. Individuals seem to have been treated differentially. Morphologically, the El Sidrón humans show a large number of neandertal lineage-derived features even though certain traits place the sample at the limits of neandertal variation. Integrating the El Sidrón human mandibles and occipital bones into the larger neandertal sample reveals a possible geographic patterning, with southern Neandertals showing broader faces with increased lower facial heights. Ancient DNA analyses have been carried out, developing an anti-contamination protocol of excavation for minimizing the risk of modern human DNA contamination. As a result both mitochondrial and nuclear DNA have been extracted from dental and osteological remains. Curiously, mtDNA comparative analyses suggest a population affinity of Iberian Peninsula Neandertals with Central European Neandertals. Nuclear DNA analyses have permitted the identification of some functional genes such as the melanocortin 1 receptor (MC1R), which regulates hair and skin pigmentation; the FOXP2, a gene involved in the development of language; and the gene involved in the ABO blood group system. Nowadays the large El Sidrón sample is the most significant neandertal sample from the Iberian Peninsula, and augments the European evolutionary lineage fossil record, supporting ecogeographical variability across neandertal populations.

Drafting Human Ancestry: What Does the Neanderthal Genome Tell Us about Hominid Evolution? Commentary on Green et al. (2010)

Ten years after the first draft versions of the human genome were announced, technical progress in both DNA sequencing and ancient DNA analyses has allowed a research team around Ed Green and Svante Pääbo to complete this task from infinitely more difficult hominid samples: a few pieces of bone originating from our closest, albeit extinct, relatives, the Neanderthals. Pulling the Neanderthal sequences out of a sea of contaminating environmental DNA impregnating the bones and at the same time avoiding the problems of contamination with modern human DNA is in itself a remarkable accomplishment. However, the crucial question in the long run is, what can we learn from such genomic data about hominid evolution?

Drafting Human Ancestry: What Does the Neanderthal Genome Tell Us about Hominid Evolution? Commentary on Green et al. (2010)

Ten years after the first draft versions of the human genome were announced, technical progress in both DNA sequencing and ancient DNA analyses has allowed a research team around Ed Green and Svante Pääbo to complete this task from infinitely more difficult hominid samples: a few pieces of bone originating from our closest, albeit extinct, relatives, the Neanderthals. Pulling the Neanderthal sequences out of a sea of contaminating environmental DNA impregnating the bones and at the same time avoiding the problems of contamination with modern human DNA is in itself a remarkable accomplishment. However, the crucial question in the long run is, what can we learn from such genomic data about hominid evolution?

Preferential access to genetic information from endogenous hominin ancient DNA and accurate quantitative SNP-typing via SPEX

The analysis of targeted genetic loci from ancient, forensic and clinical samples is usually built upon polymerase chain reaction (PCR)-generated sequence data. However, many studies have shown that PCR amplification from poor-quality DNA templates can create sequence artefacts at significant levels. With hominin (human and other hominid) samples, the pervasive presence of highly PCR-amplifiable human DNA contaminants in the vast majority of samples can lead to the creation of recombinant hybrids and other non-authentic artefacts. The resulting PCR-generated sequences can then be difficult, if not impossible, to authenticate. In contrast, single primer extension (SPEX)-based approaches can genotype single nucleotide polymorphisms from ancient fragments of DNA as accurately as modern DNA. A single SPEX-type assay can amplify just one of the duplex DNA strands at target loci and generate a multi-fold depth-of-coverage, with non-authentic recombinant hybrids reduced to undetectable levels. Crucially, SPEX-type approaches can preferentially access genetic information from damaged and degraded endogenous ancient DNA templates over modern human DNA contaminants. The development of SPEX-type assays offers the potential for highly accurate, quantitative genotyping from ancient hominin samples.

An improved PCR method for endogenous DNA retrieval in contaminated Neandertal samples based on the use of blocking primers

Neandertal skeletal remains are usually contaminated with modern human DNA derived from handling and washing of the specimens during excavation. Despite the fact that the distinct Neandertal haplotypes allow the design of specific primer pairs, for instance in most of the mitochondrial DNA (mtDNA) hypervariable region 1 (HVR1), the human contaminants can often outnumber the endogenous DNA, thus preventing a successful retrieval of Neandertal sequences. We have developed a novel PCR method, based on the use of blocking primers that preferentially bind to modern human contaminant DNA and block their amplification, and greatly improve the efficiency of Neandertal DNA retrieval. We tested the method in four El Sidrón Neandertal samples (two teeth and two bone fragments) with different contamination levels and taphonomic conditions, and we have been able to significantly increase the Neandertal yield from figures around 25.23% (5–69.6%) up to 90.18% (75.3–100%).