Proposed mechanism for the selection of lactase persistence in childhood.

Lactase persistence/persistent (LP), the ability to express the lactase enzyme in adults, is one of the most strongly selected phenotypes in humans. It is encoded by at least five genetic variants that have rapidly become widespread in various human populations. The underlying selective mechanism is not clear however, because dairy products in general are well tolerated in adults, even by lactase non-persistence/persistent (LNP) individuals. Cultural adaptations to milk consumption, notably fermentation and transformation, which can provide most of the energy (protein, fat) to both LP and LNP individuals without any associated cost seem to have been common in ancient societies. Here, we propose that selection for LP occurred through increased glucose/galactose (energy) from fresh milk intake in early childhood, a crucial period for growth. At the age of weaning indeed, lactase activity has already begun to decline in LNP individuals so the gain in energy from fresh milk by LP children represents a major fitness increase.

Why and when was lactase persistence selected for? Insights from Central Asian herders and ancient DNA.

The genetic adaptation of humans to the consumption of milk from dairying animals is one of the most emblematic cases of recent human evolution. While the phenotypic change under selection, lactase persistence (LP), is known, the evolutionary advantage conferred to persistent individuals remains obscure. One informative but underappreciated observation is that not all populations whose ancestors had access to milk genetically adapted to become lactase persistent. Indeed, Central Asian herders are mostly lactase nonpersistent, despite their significant dietary reliance on dairy products. Investigating the temporal dynamic of the -13.910:C>T Eurasian mutation associated with LP, we found that, after its emergence in Ukraine 5,960 before present (BP), the T allele spread between 4,000 BP and 3,500 BP throughout Eurasia, from Spain to Kazakhstan. The timing and geographical progression of the mutation coincides well with the migration of steppe populations across and outside of Europe. After 3,000 BP, the mutation strongly increased in frequency in Europe, but not in Asia. We propose that Central Asian herders have adapted to milk consumption culturally, by fermentation, and/or by colonic adaptation, rather than genetically. Given the possibility of a nongenetic adaptation to avoid intestinal symptoms when consuming dairy products, the puzzle then becomes this: why has LP been selected for at all?

On the Evolution of Lactase Persistence in Humans.

Lactase persistence-the ability of adults to digest the lactose in milk-varies widely in frequency across human populations. This trait represents an adaptation to the domestication of dairying animals and the subsequent consumption of their milk. Five variants are currently known to underlie this phenotype, which is monogenic in Eurasia but mostly polygenic in Africa. Despite being a textbook example of regulatory convergent evolution and gene-culture coevolution, the story of lactase persistence is far from clear: Why are lactase persistence frequencies low in Central Asian herders but high in some African hunter-gatherers? Why was lactase persistence strongly selected for even though milk processing can reduce the amount of lactose? Are there other factors, outside of an advantage of caloric intake, that contributed to the selective pressure for lactase persistence? It is time to revisit what we know and still do not know about lactase persistence in humans.

Genome-wide analysis of a collective grave from Mentesh Tepe provides insight into the population structure of early neolithic population in the South Caucasus.

Despite the localisation of the southern Caucasus at the outskirt of the Fertile Crescent, the Neolithisation process started there only at the beginning of the sixth millennium with the Shomutepe-Shulaveri culture of yet unclear origins. We present here genomic data for three new individuals from Mentesh Tepe in Azerbaijan, dating back to the beginnings of the Shomutepe-Shulaveri culture. We evidence that two juveniles, buried embracing each other, were brothers. We show that the Mentesh Tepe Neolithic population is the product of a recent gene flow between the Anatolian farmer-related population and the Caucasus/Iranian population, demonstrating that population admixture was at the core of the development of agriculture in the South Caucasus. By comparing Bronze Age individuals from the South Caucasus with Neolithic individuals from the same region, including Mentesh Tepe, we evidence that gene flows between Pontic Steppe populations and Mentesh Tepe-related groups contributed to the makeup of the Late Bronze Age and modern Caucasian populations. Our results show that the high cultural diversity during the Neolithic period of the South Caucasus deserves close genetic analysis.

Coprolites as a source of information on the genome and diet of the cave hyena.

We performed high-throughput sequencing of DNA from fossilized faeces to evaluate this material as a source of information on the genome and diet of Pleistocene carnivores. We analysed coprolites derived from the extinct cave hyena (Crocuta crocuta spelaea), and sequenced 90 million DNA fragments from two specimens. The DNA reads enabled a reconstruction of the cave hyena mitochondrial genome with up to a 158-fold coverage. This genome, and those sequenced from extant spotted (Crocuta crocuta) and striped (Hyaena hyaena) hyena specimens, allows for the establishment of a robust phylogeny that supports a close relationship between the cave and the spotted hyena. We also demonstrate that high-throughput sequencing yields data for cave hyena multi-copy and single-copy nuclear genes, and that about 50 per cent of the coprolite DNA can be ascribed to this species. Analysing the data for additional species to indicate the cave hyena diet, we retrieved abundant sequences for the red deer (Cervus elaphus), and characterized its mitochondrial genome with up to a 3.8-fold coverage. In conclusion, we have demonstrated the presence of abundant ancient DNA in the coprolites surveyed. Shotgun sequencing of this material yielded a wealth of DNA sequences for a Pleistocene carnivore and allowed unbiased identification of diet.

Genetic continuity of Indo-Iranian speakers since the Iron Age in southern Central Asia.

Since prehistoric times, southern Central Asia has been at the crossroads of the movement of people, culture, and goods. Today, the Central Asian populations are divided into two cultural and linguistic groups: the Indo-Iranian and the Turko-Mongolian groups. Previous genetic studies unveiled that migrations from East Asia contributed to the spread of Turko-Mongolian populations in Central Asia and the partial replacement of the Indo-Iranian populations. However, little is known about the origin of the latters. To shed light on this, we compare the genetic data on two current-day Indo-Iranian populations - Yaghnobis and Tajiks - with genome-wide data from published ancient individuals. The present Indo-Iranian populations from Central Asia display a strong genetic continuity with Iron Age samples from Turkmenistan and Tajikistan. We model Yaghnobis as a mixture of 93% Iron Age individual from Turkmenistan and 7% from Baikal. For the Tajiks, we observe a higher Baikal ancestry and an additional admixture event with a South Asian population. Our results, therefore, suggest that in addition to a complex history, Central Asia shows a remarkable genetic continuity since the Iron Age, with only limited gene flow.

The genome and diet of a 35,000-year-old Canis lupus specimen from the Paleolithic painted cave, Chauvet-Pont d'Arc, France.

The Chauvet-Pont-d'Arc Cave (Ardèche, France) contains some of the oldest Paleolithic paintings recorded to date, as well as thousands of bones of the extinct cave bear, and some remains and footprints of other animals. As part of the interdisciplinary research project devoted to this reference cave site, we analyzed a coprolite collected within the deep cave. AMS radiocarbon dating of bone fragments from the coprolite yielded an age of 30,450 ± 550 RC yr. BP (AAR-19656; 36,150-34,000 cal BP), similar to ages assigned to Paleolithic artwork and cave bear remains from the same cave sector. Using high-throughput shotgun DNA sequencing, we demonstrated a high abundance of canid DNA and lesser amounts of DNA from the extinct cave bear. We interpret the sample as feces from a canid that had consumed cave bear tissue. The high amount of canid DNA allowed us to reconstruct a complete canid mitochondrial genome sequence (average coverage: 83×) belonging to a deeply divergent clade of extinct mitochondrial wolf lineages that are most closely related to coeval (~35 ka) Belgian wolves. Analysis of the nuclear genome yielded a similar coverage for the X chromosome (2.4×) and the autosomes (range: 2.3-3.2×), indicating that the Chauvet canid was a female. Comparing the relationship of the nuclear genome of this specimen with that of a variety of canids, we found it more closely related to gray wolves' genomes than to other wild canid or dog genomes, especially wolf genomes from Europe and the Middle East. We conclude that the coprolite is feces from an animal within an extinct wolf lineage. The consumption of cave bear by this wolf likely explains its intrusion into the dark cave sectors and sheds new light on the paleoecology of a major cave site.

Genetic analysis of a bronze age individual from Ulug-depe (Turkmenistan).

The Oxus Civilisation (or Bactrio-Margian Archaeological Complex, BMAC) was the main archaeological culture of the Bronze Age in southern Central Asia. Paleogenetic analyses were previously conducted mainly on samples from the eastern part of BMAC. The population associated with BMAC descends from local Chalcolithic populations, with some outliers of steppe or South-Asian descent. Here, we present new genome-wide data for one individual from Ulug-depe (Turkmenistan), one of the main BMAC sites, located at the southwestern edge of the BMAC. We demonstrate that this individual genetically belongs to the BMAC cluster. Using this genome, we confirm that modern Indo-Iranian-speaking populations from Central Asia derive their ancestry from BMAC populations, with additional gene flow from the western and the Altai steppes in higher proportions among the Tajiks than the Yagnobi ethnic group.

Deciphering the complete mitochondrial genome and phylogeny of the extinct cave bear in the Paleolithic painted cave of Chauvet.

Retrieving a large amount of genetic information from extinct species was demonstrated feasible, but complete mitochondrial genome sequences have only been deciphered for the moa, a bird that became extinct a few hundred years ago, and for Pleistocene species, such as the woolly mammoth and the mastodon, both of which could be studied from animals embedded in permafrost. To enlarge the diversity of mitochondrial genomes available for Pleistocene species, we turned to the cave bear (Ursus spelaeus), whose only remains consist of skeletal elements. We collected bone samples from the Paleolithic painted cave of Chauvet-Pont d'Arc (France), which displays the earliest known human drawings, and contains thousands of bear remains. We selected a cave bear sternebra, radiocarbon dated to 32,000 years before present, from which we generated overlapping DNA fragments assembling into a 16,810-base pair mitochondrial genome. Together with the first mitochondrial genome for the brown bear western lineage, this study provides a statistically secured molecular phylogeny assessing the cave bear as a sister taxon to the brown bear and polar bear clade, with a divergence inferred to 1.6 million years ago. With the first mitochondrial genome for a Pleistocene carnivore to be delivered, our study establishes the Chauvet-Pont d'Arc Cave as a new reservoir for Paleogenetic studies. These molecular data enable establishing the chronology of bear speciation, and provide a helpful resource to rescue for genetic analysis archeological samples initially diagnosed as devoid of amplifiable DNA.

Metagenomic analysis of a blood stain from the French revolutionary Jean-Paul Marat (1743-1793).

The French revolutionary Jean-Paul Marat (1743-1793) was assassinated in 1793 in his bathtub, where he was trying to find relief from the debilitating skin disease he was suffering from. At the time of his death, Marat was annotating newspapers, which got stained with his blood and were subsequently preserved by his sister. We extracted and sequenced DNA from the blood stain and also from another section of the newspaper, which we used for comparison. Results from the human DNA sequence analyses were compatible with a heterogeneous ancestry of Marat, with his mother being of French origin and his father born in Sardinia. Metagenomic analyses of the non-human reads uncovered the presence of fungal, bacterial and low levels of viral DNA. Relying on the presence/absence of microbial species in the samples, we could cast doubt on several putative infectious agents that have been previously hypothesised as the cause of his condition but for which we detect not a single sequencing read. Conversely, some of the species we detect are uncommon as environmental contaminants and may represent plausible infective agents. Based on all the available evidence, we hypothesize that Marat may have suffered from a fungal infection (seborrheic dermatitis), possibly superinfected with bacterial opportunistic pathogens.

Chromosome evolution at the origin of the ancestral vertebrate genome.

BACKGROUND: It has been proposed that more than 450 million years ago, two successive whole genome duplications took place in a marine chordate lineage before leading to the common ancestor of vertebrates. A precise reconstruction of these founding events would provide a framework to better understand the impact of these early whole genome duplications on extant vertebrates. RESULTS: We reconstruct the evolution of chromosomes at the beginning of vertebrate evolution. We first compare 61 extant animal genomes to reconstruct the highly contiguous order of genes in a 326-million-year-old ancestral Amniota genome. In this genome, we establish a well-supported list of duplicated genes originating from the two whole genome duplications to identify tetrads of duplicated chromosomes. From this, we reconstruct a chronology in which a pre-vertebrate genome composed of 17 chromosomes duplicated to 34 chromosomes and was subject to seven chromosome fusions before duplicating again into 54 chromosomes. After the separation of the lineage of Gnathostomata (jawed vertebrates) from Cyclostomata (extant jawless fish), four more fusions took place to form the ancestral Euteleostomi (bony vertebrates) genome of 50 chromosomes. CONCLUSIONS: These results firmly establish the occurrence of two whole genome duplications in the lineage that precedes the ancestor of vertebrates, resolving in particular the ambiguity raised by the analysis of the lamprey genome. This work provides a foundation for studying the evolution of vertebrate chromosomes from the standpoint of a common ancestor and particularly the pattern of duplicate gene retention and loss that resulted in the gene composition of extant vertebrate genomes.

[Importance of intestinal paleomicrobiome study for contemporaneous medical problematics]. / Fæces vivos docent - Microbiome intestinal ancien et problématiques médicales contemporaines.

Human gut microbiome composition and diversity increasingly appear as a reliable marker of human evolution within his environment, and of health and its alteration (concept of dysbiosis); as a matter of fact, it can be considered as a strong marker of the disease status of individuals. Thus, in retrospect, the capacity to profile the gut microbiome would offer a great opportunity to identify individual and societal changes to which ancient populations were exposed. A global and diachronic view of the gut microbiome evolution is necessary in order to highlight the potential role of environmental factors or human habits in this process. However, to make the most of its contribution, archaeo-microbiology should aim at being as exhaustive as possible, encompassing parasites which have likely played a major role in the development of the mammalian immune system, and viruses.

Nodular Worm Infections in Wild Non-human Primates and Humans Living in the Sebitoli Area (Kibale National Park, Uganda): Do High Spatial Proximity Favor Zoonotic Transmission?

BACKGROUND: Nodular Oesophagostomum genus nematodes are a major public health concern in some African regions because they can be lethal to humans. Their relatively high prevalence in people has been described in Uganda recently. While non-human primates also harbor Oesophagostomum spp., the epidemiology of this oesophagostomosis and the role of these animals as reservoirs of the infection in Eastern Africa are not yet well documented. METHODOLOGY/PRINCIPAL FINDINGS: The present study aimed to investigate Oesophagostomum infection in terms of parasite species diversity, prevalence and load in three non-human primates (Pan troglodytes, Papio anubis, Colobus guereza) and humans living in close proximity in a forested area of Sebitoli, Kibale National Park (KNP), Uganda. The molecular phylogenetic analyses provided the first evidence that humans living in the Sebitoli area harbored O. stephanostomum, a common species in free-ranging chimpanzees. Chimpanzees were also infected by O. bifurcum, a common species described in human populations throughout Africa. The recently described Oesophagostomum sp. found in colobine monkeys and humans and which was absent from baboons in the neighboring site of Kanyawara in KNP (10 km from Sebitoli), was only found in baboons. Microscopic analyses revealed that the infection prevalence and parasite load in chimpanzees were significantly lower in Kanyawara than in Sebitoli, an area more impacted by human activities at its borders. CONCLUSIONS/SIGNIFICANCE: Three different Oesophagostomum species circulate in humans and non-human primates in the Sebitoli area and our results confirm the presence of a new genotype of Oesophagostomum recently described in Uganda. The high spatiotemporal overlap between humans and chimpanzees in the studied area coupled with the high infection prevalence among chimpanzees represent factors that could increase the risk of transmission for O. stephanostomum between the two primate species. Finally, the importance of local-scale research for zoonosis risk management is important because environmental disturbance and species contact can differ, leading to different parasitological profiles between sites that are close together within the same forest patches.