The evolutionary history of Neanderthal and Denisovan Y chromosomes

Ancient DNA has provided new insights into many aspects of human history. However, we lack comprehensive studies of the Y chromosomes of Denisovans and Neanderthals because the majority of specimens that have been sequenced to sufficient coverage are female. Sequencing Y chromosomes from two Denisovans and three Neanderthals shows that the Y chromosomes of Denisovans split around 700 thousand years ago from a lineage shared by Neanderthals and modern human Y chromosomes, which diverged from each other around 370 thousand years ago. The phylogenetic relationships of archaic and modern human Y chromosomes differ from the population relationships inferred from the autosomal genomes and mirror mitochondrial DNA phylogenies, indicating replacement of both the mitochondrial and Y chromosomal gene pools in late Neanderthals. This replacement is plausible if the low effective population size of Neanderthals resulted in an increased genetic load in Neanderthals relative to modern humans.Q.F. was supported by funding from the Chinese Academy of Sciences (XDB26000000) and the National Natural Science Foundation of China (91731303, 41925009, 41630102). A.R. was funded by Spanish government (MICINN/ FEDER) (grant number CGL2016-75109-P). The reassessment of the Spy collection by H.R., I.C., and P.S. was supported by the Belgian Science Policy Office (BELSPO 2004-2007, MO/36/0112). M.V.S., M.B.K., and A.P.D. were supported by the Russian Foundation for Basic Research (RFBR 17-29-04206). This study was funded by the Max Planck Society and the European Research Council (grant agreement number 694707)

Analysis of the effectiveness of interventions used during the 2009 A/H1N1 influenza pandemic

<p>Abstract</p> <p>Background</p> <p>Following the emergence of the A/H1N1 2009 influenza pandemic, public health interventions were activated to lessen its potential impact. Computer modelling and simulation can be used to determine the potential effectiveness of the social distancing and antiviral drug therapy interventions that were used at the early stages of the pandemic, providing guidance to public health policy makers as to intervention strategies in future pandemics involving a highly pathogenic influenza strain.</p> <p>Methods</p> <p>An individual-based model of a real community with a population of approximately 30,000 was used to determine the impact of alternative interventions strategies, including those used in the initial stages of the 2009 pandemic. Different interventions, namely school closure and antiviral strategies, were simulated in isolation and in combination to form different plausible scenarios. We simulated epidemics with reproduction numbers R₀of 1.5, which aligns with estimates in the range 1.4-1.6 determined from the initial outbreak in Mexico.</p> <p>Results</p> <p>School closure of 1 week was determined to have minimal effect on reducing overall illness attack rate. Antiviral drug treatment of 50% of symptomatic cases reduced the attack rate by 6.5%, from an unmitigated rate of 32.5% to 26%. Treatment of diagnosed individuals combined with additional household prophylaxis reduced the final attack rate to 19%. Further extension of prophylaxis to close contacts (in schools and workplaces) further reduced the overall attack rate to 13% and reduced the peak daily illness rate from 120 to 22 per 10,000 individuals. We determined the size of antiviral stockpile required; the ratio of the required number of antiviral courses to population was 13% for the treatment-only strategy, 25% for treatment and household prophylaxis and 40% for treatment, household and extended prophylaxis. Additional simulations suggest that coupling school closure with the antiviral strategies further reduces epidemic impact.</p> <p>Conclusions</p> <p>These results suggest that the aggressive use of antiviral drugs together with extended school closure may substantially slow the rate of influenza epidemic development. These strategies are more rigorous than those actually used during the early stages of the relatively mild 2009 pandemic, and are appropriate for future pandemics that have high morbidity and mortality rates.</p

Game Theory of Social Distancing in Response to an Epidemic

Social distancing practices are changes in behavior that prevent disease transmission by reducing contact rates between susceptible individuals and infected individuals who may transmit the disease. Social distancing practices can reduce the severity of an epidemic, but the benefits of social distancing depend on the extent to which it is used by individuals. Individuals are sometimes reluctant to pay the costs inherent in social distancing, and this can limit its effectiveness as a control measure. This paper formulates a differential-game to identify how individuals would best use social distancing and related self-protective behaviors during an epidemic. The epidemic is described by a simple, well-mixed ordinary differential equation model. We use the differential game to study potential value of social distancing as a mitigation measure by calculating the equilibrium behaviors under a variety of cost-functions. Numerical methods are used to calculate the total costs of an epidemic under equilibrium behaviors as a function of the time to mass vaccination, following epidemic identification. The key parameters in the analysis are the basic reproduction number and the baseline efficiency of social distancing. The results show that social distancing is most beneficial to individuals for basic reproduction numbers around 2. In the absence of vaccination or other intervention measures, optimal social distancing never recovers more than 30% of the cost of infection. We also show how the window of opportunity for vaccine development lengthens as the efficiency of social distancing and detection improve

Neandertal and Denisovan DNA from Pleistocene sediments.

Although a rich record of Pleistocene human-associated archaeological assemblages exists, the scarcity of hominin fossils often impedes the understanding of which hominins occupied a site. Using targeted enrichment of mitochondrial DNA we show that cave sediments represent a rich source of ancient mammalian DNA that often includes traces of hominin DNA, even at sites and in layers where no hominin remains have been discovered. By automation-assisted screening of numerous sediment samples we detect Neandertal DNA in eight archaeological layers from four caves in Eurasia. In Denisova Cave we retrieved Denisovan DNA in a Middle Pleistocene layer near the bottom of the stratigraphy. Our work opens the possibility to detect the presence of hominin groups at sites and in areas where no skeletal remains are found

Analysis of Human Accelerated DNA Regions Using Archaic Hominin Genomes

Several previous comparisons of the human genome with other primate and vertebrate genomes identified genomic regions that are highly conserved in vertebrate evolution but fast-evolving on the human lineage. These human accelerated regions (HARs) may be regions of past adaptive evolution in humans. Alternatively, they may be the result of non-adaptive processes, such as biased gene conversion. We captured and sequenced DNA from a collection of previously published HARs using DNA from an Iberian Neandertal. Combining these new data with shotgun sequence from the Neandertal and Denisova draft genomes, we determine at least one archaic hominin allele for 84% of all positions within HARs. We find that 8% of HAR substitutions are not observed in the archaic hominins and are thus recent in the sense that the derived allele had not come to fixation in the common ancestor of modern humans and archaic hominins. Further, we find that recent substitutions in HARs tend to have come to fixation faster than substitutions elsewhere in the genome and that substitutions in HARs tend to cluster in time, consistent with an episodic rather than a clock-like process underlying HAR evolution. Our catalog of sequence changes in HARs will help prioritize them for functional studies of genomic elements potentially responsible for modern human adaptations

Embodying the mind and representing the body

Does the existence of body representations undermine the explanatory role of the body? Or do certain types of representation depend so closely upon the body that their involvement in a cognitive task implicates the body itself? In the introduction of this special issue we explore lines of tension and complement that might hold between the notions of embodiment and body representations, which remain too often neglected or obscure. To do so, we distinguish two conceptions of embodiment that either put weight on the explanatory role of the body itself or body representations. We further analyse how and to what extent body representations can be said to be embodied. Finally, we give an overview of the full volume articulated around foundational issues (How should we define the notion of embodiment? To what extent and in what sense is embodiment compatible with representationalism? To what extent and in what sense are sensorimotor approaches similar to behaviourism?) and their applications in several cognitive domains (perception, concepts, selfhood, social cognition)

Successful Amelioration of Mitochondrial Optic Neuropathy Using the Yeast NDI1 Gene in a Rat Animal Model

Background: Leber’s hereditary optic neuropathy (LHON) is a maternally inherited disorder with point mutations in mitochondrial DNA which result in loss of vision in young adults. The majority of mutations reported to date are within the genes encoding the subunits of the mitochondrial NADH-quinone oxidoreductase, complex I. Establishment of animal models of LHON should help elucidate mechanism of the disease and could be utilized for possible development of therapeutic strategies. Methodology/Principal Findings: We established a rat model which involves injection of rotenone-loaded microspheres into the optic layer of the rat superior colliculus. The animals exhibited the most common features of LHON. Visual loss was observed within 2 weeks of rotenone administration with no apparent effect on retinal ganglion cells. Death of retinal ganglion cells occurred at a later stage. Using our rat model, we investigated the effect of the yeast alternative NADH dehydrogenase, Ndi1. We were able to achieve efficient expression of the Ndi1 protein in the mitochondria of all regions of retinal ganglion cells and axons by delivering the NDI1 gene into the optical layer of the superior colliculus. Remarkably, even after the vision of the rats was severely impaired, treatment of the animals with the NDI1 gene led to a complete restoration of the vision to the normal level. Control groups that received either empty vector or the GFP gene had no effects

The evolutionary history of Neandertal and Denisovan Y chromosomes

Ancient DNA has allowed the study of various aspects of human history in unprecedented detail. However, because the majority of archaic human specimens preserved well enough for genome sequencing have been female, comprehensive studies of Y chromosomes of Denisovans and Neandertals have not yet been possible. Here we present sequences of the first Denisovan Y chromosomes (Denisova 4 and Denisova 8), as well as the Y chromosomes of three late Neandertals (Spy 94a, Mezmaiskaya 2 and El Sidrón 1253). We find that the Denisovan Y chromosomes split around 700 thousand years ago (kya) from a lineage shared by Neandertal and modern human Y chromosomes, which diverged from each other around 370 kya. The phylogenetic relationships of archaic and modern human Y chromosomes therefore differ from population relationships inferred from their autosomal genomes, and mirror the relationships observed on the level of mitochondrial DNA. This provides strong evidence that gene flow from an early lineage related to modern humans resulted in the replacement of both the mitochondrial and Y chromosomal gene pools in late Neandertals. Although unlikely under neutrality, we show that this replacement is plausible if the low effective population size of Neandertals resulted in an increased genetic load in their Y chromosomes and mitochondrial DNA relative to modern humans.Q.F. was supported by funding from the Chinese Academy of Sciences (XDB26000000), and the National Natural Science Foundation of China (91731303, 41925009,41630102). A.R. was funded by Spanish government (MICINN/FEDER), grant number CGL2016-75109-P. The reassessment of the Spy collection by H.R., I.C. and P.S. was supported by the Belgian Science Policy Office (BELSPO 2004-2007, MO/36/0112). M.S., M.K. and A.D. were supported by the Russian Foundation for Basic Research (RFBR 17-29-04206). This study was funded by the Max Planck Society and the European Research Council (grant agreement number 694707).N