Showing papers by "Collège de France published in 2022"

The genomic signatures of natural selection in admixed human populations

Abstract: Admixture has been a pervasive phenomenon in human history, extensively shaping the patterns of population genetic diversity. There is increasing evidence to suggest that admixture can also facilitate genetic adaptation to local environments, i.e., admixed populations acquire beneficial mutations from source populations, a process that we refer to as "adaptive admixture." However, the role of adaptive admixture in human evolution and the power to detect it remain poorly characterized. Here, we use extensive computer simulations to evaluate the power of several neutrality statistics to detect natural selection in the admixed population, assuming multiple admixture scenarios. We show that statistics based on admixture proportions, Fadm and LAD, show high power to detect mutations that are beneficial in the admixed population, whereas other statistics, including iHS and FST, falsely detect neutral mutations that have been selected in the source populations only. By combining Fadm and LAD into a single, powerful statistic, we scanned the genomes of 15 worldwide, admixed populations for signatures of adaptive admixture. We confirm that lactase persistence and resistance to malaria have been under adaptive admixture in West Africans and in Malagasy, North Africans, and South Asians, respectively. Our approach also uncovers other cases of adaptive admixture, including APOL1 in Fulani nomads and PKN2 in East Indonesians, involved in resistance to infection and metabolism, respectively. Collectively, our study provides evidence that adaptive admixture has occurred in human populations whose genetic history is characterized by periods of isolation and spatial expansions resulting in increased gene flow.

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Abstract: The recently discovered kagome metals ${\mathrm{KV}}_{3}{\mathrm{Sb}}_{5}$, ${\mathrm{RbV}}_{3}{\mathrm{Sb}}_{5}$, and ${\mathrm{CsV}}_{3}{\mathrm{Sb}}_{5}$ exhibit a unique charge density wave state which hosts both superconductivity and a large anomalous Hall response. The microscopic mechanisms that underlie these phenomena have not been fully understood because the structure of the charge density wave order has not been completely determined. Previous theoretical results show that the parent $P6/mmm$ phase of these materials has phonon instabilities at the $M(\frac{1}{2},0,0)$ and $L(\frac{1}{2},0,\frac{1}{2})$ points in their Brillouin zone, but the energetics of all the low-symmetry phases that can arise due to the phonon instabilities was not investigated. Here, I perform such a search for the lowest-energy structure of these materials using first-principles calculations. Group-theoretical analysis shows that there are 17 different distortions that are possible due to the phonon instabilities. I generated these structures for the three compounds and performed full structural relaxations that minimize the atomic forces and lattice stresses. I find that the $Fmmm$ phase with the order parameter ${M}_{1}^{+}(a,0,0)+{L}_{2}^{\ensuremath{-}}(0,b,b)$ has the lowest energy among these possibilities in all three compounds. However, the $Fmmm$ exhibits a dynamical instability at its $Z(0,0,1)$ point, which corresponds to a doubly degenerate unstable phonon mode at the $A(0,0,\frac{1}{2})$ point in the parent $P6/mmm$ phase. The $A$ point has only one element in its star, and condensation of the instability at this point leads to a base-centered-orthorhombic structure with the space group $Cmcm$ and $4Q$ order parameter ${M}_{1}^{+}(a,0,0)+{L}_{2}^{\ensuremath{-}}(0,b,b)+{A}_{6}^{+}(\frac{1}{2}c,\frac{\ensuremath{-}\sqrt{3}}{2}c)$. A characteristic signature of this charge order is the absence of the mirror symmetry perpendicular to the $b$ axis in individual kagome layers, whose experimental observation below the structural transition temperature would be a strong indication that the $Cmcm$ structure describes the charge density wave state of these materials.

The immune factors driving DNA methylation variation in human blood

Abstract: Abstract Epigenetic changes are required for normal development, yet the nature and respective contribution of factors that drive epigenetic variation in humans remain to be fully characterized. Here, we assessed how the blood DNA methylome of 884 adults is affected by DNA sequence variation, age, sex and 139 factors relating to life habits and immunity. Furthermore, we investigated whether these effects are mediated or not by changes in cellular composition, measured by deep immunophenotyping. We show that DNA methylation differs substantially between naïve and memory T cells, supporting the need for adjustment on these cell-types. By doing so, we find that latent cytomegalovirus infection drives DNA methylation variation and provide further support that the increased dispersion of DNA methylation with aging is due to epigenetic drift. Finally, our results indicate that cellular composition and DNA sequence variation are the strongest predictors of DNA methylation, highlighting critical factors for medical epigenomics studies.

Molecular Inhibition for Selective CO ₂ Conversion

Abstract: Electrochemical CO2 reduction presents a sustainable route to the production of chemicals and fuels. Achieving a narrow product distribution with heterogeneous Cu catalysts is challenging and conventional material modifications offer limited control over selectivity. Here, we show that surface-immobilised molecular species can act as inhibitors for specific carbon products to provide rational control over product distributions. Combined experimental and computational results showed that anchoring of a thiol-functionalised pyridine on Cu destabilises a surface-bound reaction intermediate to energetically block a CO-producing pathway, thereby favouring formate production. The nitrogen atom was shown to be essential to the inhibition mechanism. The ability of molecules to control selectivity through inhibition of specific reaction pathways offers a unique approach to rationally modify heterogeneous catalysts.

Genetic adaptation to pathogens and increased risk of inflammatory disorders in post-Neolithic Europe

Abstract: ABSTRACT Ancient genomics can directly detect human genetic adaptation to environmental cues. However, it remains unclear how pathogens have exerted selective pressures on human genome diversity across different epochs and affected present-day inflammatory disease risk. Here, we use an ancestry-aware approximate Bayesian computation framework to estimate the nature, strength, and time of onset of selection acting on 2,879 ancient and modern European genomes from the last 10,000 years. We found that the bulk of genetic adaptation occurred after the start of the Bronze Age, <4,500 years ago, and was enriched in genes relating to host-pathogen interactions. Furthermore, we detected directional selection acting on specific leukocytic lineages and experimentally demonstrated that the strongest negatively selected immunity gene variant — the lipopolysaccharide-binding protein gene ( LBP ) D283G — is hypomorphic. Finally, our analyses suggest that the risk of inflammatory disorders has progressively increased in post-Neolithic Europeans, partly due to antagonistic pleiotropy following genetic adaptation to pathogens.

Sequential And Directional Insulation By Conserved CTCF Sites Underlies The <i>Hox</i> Timer In Pseudo-Embryos

Abstract: ABSTRACT During development, Hox genes are activated in a time sequence following their relative positions on their clusters, leading to the proper identities of structures along the rostral to caudal axis. To understand the mechanism operating this Hox timer, we used ES-cells derived stembryos and show that the core of the process involves the start of transcription at the 3’ part of the cluster, following Wnt signaling, and the concomitant loading of cohesin complexes on the transcribed DNA segments, i.e., with an asymmetric distribution along the gene cluster. Chromatin extrusion then occurs with successively more posterior CTCF sites acting as transient insulators, thus generating a progressive time-delay in the activation of more 5’-located genes due to long-range contacts with a flanking TAD. Mutant stembryos support this model and reveal that the iterated presence of evolutionary conserved and regularly spaced intergenic CTCF sites control the precision and the pace of this temporal mechanism.

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Abstract: I present first principles calculations of the phonon dispersions of TiSe$_2$ in the $P\overline{3}c1$ phase, which is the currently accepted low-temperature structure of this material. They show weak instabilities in the acoustic branches in the out-of-plane direction, suggesting that this phase may not be the true ground state. To find the lowest energy structure, I study the energetics of all possible distorted structures corresponding to the isotropy subgroups of $P\overline{3}m1$ for the $M_1^-$ and $L_1^-$ phonon instabilities present in this high-temperature phase at $q = (\frac{1}{2},0,0)$ and $(\frac{1}{2},0,\frac{1}{2})$, respectively. I was able to stabilize 10 different structures that are lower in energy relative to the parent $P\overline{3}m1$ phase, including two monoclinic structures more energetically stable than the $P\overline{3}c1$ phase. The lowest energy structure has the space group $C2$ with the order parameter $M_1^- (a,0,0) + L_1^- (0,b,b)$. This structure lacks inversion symmetry, and its primitive unit cell has 12 atoms.

Molecular Inhibition for Selective CO ₂ Conversion

Abstract: Electrochemical CO2 reduction presents a sustainable route to the production of chemicals and fuels. Achieving a narrow product distribution with heterogeneous Cu catalysts is challenging and conventional material modifications offer limited control over selectivity. Here, we show that surface-immobilised molecular species can act as inhibitors for specific carbon products to provide rational control over product distributions. Combined experimental and computational results showed that anchoring of a thiol-functionalised pyridine on Cu destabilises a surface-bound reaction intermediate to energetically block a CO-producing pathway, thereby favouring formate production. The nitrogen atom was shown to be essential to the inhibition mechanism. The ability of molecules to control selectivity through inhibition of specific reaction pathways offers a unique approach to rationally modify heterogeneous catalysts.

Context-Dependent Enhancer Function Revealed by Targeted Inter-TAD Relocation

Abstract: ABSTRACT The expression of genes with a key function during development is frequently controlled by large regulatory landscapes containing multiple enhancer elements. These landscapes often match Topologically Associating Domains (TADs) and sometimes integrate range of similar enhancers, thus leading to TADs having a global regulatory specificity. To assess the relative functional importance of enhancer sequences versus the regulatory domain they are included in, we set out to transfer one particular enhancer sequence from its native domain into a TAD with a closely related, yet different functional specificity. We used Hoxd genes and their biphasic regulation during limb development as a paradigm, since they are first activated in proximal limb cells by enhancers located in one TAD, which is then silenced at the time when the neighboring TAD starts to activate its enhancers in distal limb cells. We introduced a strong distal limb enhancer into the ‘proximal limb TAD’ and found that its new context strongly suppresses its distal specificity, even though it continues to be bound by HOX13 transcription factors, which normally are responsible for this activity. Using local genetic alterations and chromatin conformation measurements, we see that the enhancer is capable of interacting with target genes, with a pattern comparable to its adoptive neighborhood of enhancers. Its activity in distal limb cells can be rescued only when a large portion of the surrounding environment is removed. These results indicate that, at least in some cases, the functioning of enhancer elements is subordinated to the local chromatin context, which can exert a dominant control over its activity.

Shuttling Homeoproteins and Their Biological Significance.

Abstract: The transfer of homeoprotein transcription factors is at the origin of the discovery of Penetratin, one of the first transduction peptides allowing for the addressing of hydrophilic cargoes to the cell cytoplasm and nucleus. Beyond this important technological application, homeoprotein transduction has now been confirmed for more than 150 members of this family, and represents an intriguing mode of signaling for which actual in vivo functions are known for a handful of these proteins. Because homeoproteins are expressed in all eukaryotes, and their intercellular transfer occurs both in plants and animals, it is likely that this signaling activity appeared before the separation between plants, fungi, and animals, and is therefore very ancient. These aspects are discussed in the present review, with an accent placed on evolution and on the comparison of homeoprotein signaling between species belonging to distinct phyla.

The genomic landscape of contemporary western Remote Oceanians

Abstract: SUMMARY The Vanuatu archipelago served as a gateway to Remote Oceania during one of the most extensive human migrations to uninhabited lands, ~3,000 years ago. Ancient DNA studies suggest an initial settlement by East Asian-related peoples that was quickly followed by the arrival of Papuan-related populations, leading to a major population turnover. Yet, there is uncertainty over the population processes and the sociocultural factors that have shaped the genomic diversity of ni-Vanuatu, who present nowadays among the world’s highest linguistic and cultural diversity. Here, we report new genome-wide data for 1,433 contemporary ni-Vanuatu from 29 different islands, including 287 couples. We find that ni-Vanuatu derive their East Asian- and Papuan-related ancestry from the same source populations and descend from relatively synchronous, sex-biased admixture events that occurred ~1,700-2,300 years ago, indicating a peopling history common to all the archipelago. However, East Asian-related ancestry proportions differ markedly across islands, suggesting that the Papuan-related population turnover was geographically uneven. Furthermore, we detect Polynesian ancestry arriving ~600-1,000 years ago to South Vanuatu in both Polynesian- and non-Polynesian-speaking populations. Lastly, we provide evidence for a tendency of spouses to carry similar genetic ancestry, when accounting for relatedness avoidance. The signal is not driven by strong genetic effects of specific loci or trait-associated variants, suggesting that it results instead from social assortative mating. Altogether, our findings provide insight into both the genetic history of ni-Vanuatu populations and how sociocultural processes have shaped the diversity of their genomes.

Feeds, Ration Formulation: Transition Cow Feeding and Management on Pasture Systems

Abstract: The transition period is defined as the 6–8 weeks encompassing late pregnancy and early lactation, involving coordinated changes across multiple tissues and a large increase in nutrient requirements. Metabolic and genomic profiling have confirmed that the physiological, biochemical and immunological changes that occur during the transition from pregnancy to lactation occur in moderate yielding cows grazing fresh pasture as well as high yielding housed cows consuming a total mixed ration (TMR). However, differences in the basal diet and the practicalities around how the diet can be managed dictate that the management of the pasture-based transition cow is considered separately to her housed contemporaries.

« In partibus fidelium ». Missions du Levant et connaissance de l’Orient chrétien (XIXe-XXIe siècles)

Abstract: En quoi les missions chrétiennes du Levant ont-elles été des lieux de production de savoirs « orientaux » ? Comment ces connaissances ont-elles circulé de part et d’autre de la Méditerranée ? Comment ont-elles été reformulées et réappropriées localement ? Cet ouvrage se penche sur l’assimilation en Europe de connaissances relatives aux cultures chrétiennes-orientales et sur le rôle que les missions ont joué dans ce processus. Collectés et élaborés dans les grandes bibliothèques et universi...

Possible structural quantum criticality tuned by rare-earth ion substitution in infinite-layer nickelates

Abstract: I show the infinite-layer rare-earth nickelates are near a structural quantum critical point by mapping the energetics of their structural instabilities using first priniciples calculations. I first confirm previous results that show a phonon instability in the $P4/mmm$ phase leading to the $I4/mcm$ structure for $R$NiO$_2$ with $R$ = Sm--Lu. I then study the non-spin-polarized phonon dispersions of the $I4/mcm$ phase and find that they exhibit rare-earth size dependent instabilities at the $X$ and $M$ points for materials with $R$ = Eu--Lu. Group-theoretical analysis was used to enumerate all the isotropy subroups due to these instablities, and the distorted structures corresponding to their order parameters were generated using the eigenvectors of the unstable phonons. These structures were then fully relaxed by minimizing both the atomic forces and lattice stresses. I was able to stabilize only five out of the twelve possible distortions. The $Pbcn$ isotropy subgroup with the $M_5^+(a,a)$ order parameter shows noticeable energy gain relative to other distortions for the compounds with late rare-earth ions. However, the order parameter of the lowest-energy phase switches first to $X_2^- (0,a) + M_5^+ (b,0)$ and then to $X_2^- (0,a)$ as the size of the rare-earth ion is progressively increased. Additionally, several distorted structures lie close in energy for the early members of this series. These features of the structural energetics persist even when antiferromagnetism is allowed. Such a competition between different order parameters that can be tuned by rare-earth ion substitution suggests that any structural transition that could arise from the phonon instabilities present in these materials can be suppressed to 0 K.

Groupes de Coxeter finis: Centralisateurs d’involutions

Abstract: We give a case-by-case description of the centralizers of involutions in a finite Coxeter group.

The First Case of Coxiella Burnetti Infection Detected Through Bone Marrow Biopsy in Vietnam

Abstract: Coxiella burnetii is an obligate intracellular bacterium that causes the zoonotic infectious disease, Q fever. The common clinical presentation is fever, hepatitis, and pneumonia; laboratory examination could reveal pancytopenia, elevated liver enzymes. In bone marrow, many fibrin ring granulomas, also known as "Doughnut" granulomas can be seen and suggest the diagnosis of Q fever. However, these bone marrow granulomas can also be presented in infectious diseases by other pathogens such as EBV, CMV, and HBV; therefore, other serology or PCR-based tests are needed to confirm the diagnosis of Q fever. We report the first case of acute Q fever in Vietnam, presented as a fever of unknown origin with hepatitis in a 53-year-old male patient. A bone marrow biopsy was performed and showed various fibrin ring granulomas; therefore, Coxiella was suspected and the diagnosis was confirmed by PCR. Some infectious diseases can cause specific changes in the bone marrow, such as Doughnut granulomas in Q fever. These features can help direct the diagnosis and decide earlier treatment for the patient.

1 Introduction: “On the margins of the marginal” – Why are there so few specialists in Central Asian photography of the imperial and early Soviet period?

Abstract: 1 Introduction: “On the margins of the marginal” – Why are there so few specialists in Central Asian photography of the imperial and early Soviet period? was published in Photographing Central Asia on page 1.