scholarly journals The limits of long-term selection against Neandertal introgression

2018 ◽  
Author(s):  
Martin Petr ◽  
Svante Pääbo ◽  
Janet Kelso ◽  
Benjamin Vernot
Keyword(s):  
Negative Selection ◽  
Western Europe ◽  
Modern Human ◽  
Model Parameters ◽  
Modern Humans ◽  
High Coverage ◽  
The Past ◽  
Deleterious Alleles ◽  
Wide Range

AbstractSeveral studies have suggested that introgressed Neandertal DNA was subjected to negative selection in modern humans due to deleterious alleles that had accumulated in the Neandertals after they split from the modern human lineage. A striking observation in support of this is an apparent monotonic decline in Neandertal ancestry observed in modern humans in Europe over the past 45 thousand years. Here we show that this apparent decline is an artifact caused by gene flow between West Eurasians and Africans, which is not taken into account by statistics previously used to estimate Neandertal ancestry. When applying a more robust statistic that takes advantage of two high-coverage Neandertal genomes, we find no evidence for a change in Neandertal ancestry in Western Europe over the past 45 thousand years. We use whole-genome simulations of selection and introgression to investigate a wide range of model parameters, and find that negative selection is not expected to cause a significant long-term decline in genome-wide Neandertal ancestry. Nevertheless, these models recapitulate previously observed signals of selection against Neandertal alleles, in particular a depletion of Neandertal ancestry in conserved genomic regions that are likely to be of functional importance. Thus, we find that negative selection against Neandertal ancestry has not played as strong a role in recent human evolution as had previously been assumed.

scholarly journals Limits of long-term selection against Neandertal introgression

2019 ◽  
Vol 116 (5) ◽  
pp. 1639-1644 ◽  
Author(s):  
Martin Petr ◽  
Svante Pääbo ◽  
Janet Kelso ◽  
Benjamin Vernot
Keyword(s):  
Negative Selection ◽  
Modern Human ◽  
Model Parameters ◽  
Human Populations ◽  
Modern Humans ◽  
High Coverage ◽  
Protein Coding ◽  
The Past ◽  
Wide Range

Several studies have suggested that introgressed Neandertal DNA was subjected to negative selection in modern humans. A striking observation in support of this is an apparent monotonic decline in Neandertal ancestry observed in modern humans in Europe over the past 45,000 years. Here, we show that this decline is an artifact likely caused by gene flow between modern human populations, which is not taken into account by statistics previously used to estimate Neandertal ancestry. When we apply a statistic that avoids assumptions about modern human demography by taking advantage of two high-coverage Neandertal genomes, we find no evidence for a change in Neandertal ancestry in Europe over the past 45,000 years. We use whole-genome simulations of selection and introgression to investigate a wide range of model parameters and find that negative selection is not expected to cause a significant long-term decline in genome-wide Neandertal ancestry. Nevertheless, these models recapitulate previously observed signals of selection against Neandertal alleles, in particular the depletion of Neandertal ancestry in conserved genomic regions. Surprisingly, we find that this depletion is strongest in regulatory and conserved noncoding regions and in the most conserved portion of protein-coding sequences.

Chinese Medicine Protein and Peptide in Gene and Cell Therapy

2019 ◽  
Vol 20 (3) ◽  
pp. 251-264 ◽  
Author(s):  
Yinlu Feng ◽  
Zifei Yin ◽  
Daniel Zhang ◽  
Arun Srivastava ◽  
Chen Ling
Keyword(s):  
Chinese Medicine ◽  
Cell Therapy ◽  
Future Research ◽  
The Past ◽  
Promising Strategy ◽  
Wide Range ◽  
New Directions ◽  
Gene And Cell Therapy ◽  
Proteins And Peptides

The success of gene and cell therapy in clinic during the past two decades as well as our expanding ability to manipulate these biomaterials are leading to new therapeutic options for a wide range of inherited and acquired diseases. Combining conventional therapies with this emerging field is a promising strategy to treat those previously-thought untreatable diseases. Traditional Chinese medicine (TCM) has evolved for thousands of years in China and still plays an important role in human health. As part of the active ingredients of TCM, proteins and peptides have attracted long-term enthusiasm of researchers. More recently, they have been utilized in gene and cell therapy, resulting in promising novel strategies to treat both cancer and non-cancer diseases. This manuscript presents a critical review on this field, accompanied with perspectives on the challenges and new directions for future research in this emerging frontier.

Cognitive impairment in long-term benzodiazepine users

1988 ◽  
Vol 18 (2) ◽  
pp. 365-374 ◽  
Author(s):  
Susan Golombok ◽  
Parimala Moodley ◽  
Malcolm Lader
Keyword(s):  
Neuropsychological Tests ◽  
Matched Control ◽  
Control Group ◽  
Therapeutic Practice ◽  
The Past ◽  
Visual Spatial ◽  
Wide Range ◽  
High Doses ◽  
One Year

SynopsisIn view of the very extensive and often prolonged use of benzodiazepines in therapeutic practice, this study was designed to investigate whether or not cognitive ability is impaired in longterm benzodiazepine users, and to determine the nature and extent of any deficit. Fifty patients currently taking benzodiazepines for at least one year, thirty-four who had stopped taking benzodiazepines, and a matched control group of subjects who had never taken benzodiazepines or who had taken benzodiazepines in the past for less than one year were administered a battery of neuropsychological tests designed to measure a wide range of cognitive functions. It was found that patients taking high doses of benzodiazepines for long periods of time perform poorly on tasks involving visual-spatial ability and sustained attention. This is consistent with deficits in posterior cortical cognitive function.

scholarly journals Archaic mitochondrial DNA inserts in modern day nuclear genomes

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Robert Bücking ◽  
Murray P Cox ◽  
Georgi Hudjashov ◽  
Lauri Saag ◽  
Herawati Sudoyo ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Nuclear Dna ◽  
Modern Human ◽  
Sub Saharan Africa ◽  
Next Generation Sequencing Data ◽  
Human Populations ◽  
Sequencing Data ◽  
Modern Humans ◽  
High Coverage ◽  
Nuclear Genomes

Abstract Background Traces of interbreeding of Neanderthals and Denisovans with modern humans in the form of archaic DNA have been detected in the genomes of present-day human populations outside sub-Saharan Africa. Up to now, only nuclear archaic DNA has been detected in modern humans; we therefore attempted to identify archaic mitochondrial DNA (mtDNA) residing in modern human nuclear genomes as nuclear inserts of mitochondrial DNA (NUMTs). Results We analysed 221 high-coverage genomes from Oceania and Indonesia using an approach which identifies reads that map both to the nuclear and mitochondrial DNA. We then classified reads according to the source of the mtDNA, and found one NUMT of Denisovan mtDNA origin, present in 15 analysed genomes; analysis of the flanking region suggests that this insertion is more likely to have happened in a Denisovan individual and introgressed into modern humans with the Denisovan nuclear DNA, rather than in a descendant of a Denisovan female and a modern human male. Conclusions Here we present our pipeline for detecting introgressed NUMTs in next generation sequencing data that can be used on genomes sequenced in the future. Further discovery of such archaic NUMTs in modern humans can be used to detect interbreeding between archaic and modern humans and can reveal new insights into the nature of such interbreeding events.

scholarly journals A 40-million-year history of atmospheric CO 2

2013 ◽  
Vol 371 (2001) ◽  
pp. 20130096 ◽  
Author(s):  
Yi Ge Zhang ◽  
Mark Pagani ◽  
Zhonghui Liu ◽  
Steven M. Bohaty ◽  
Robert DeConto
Keyword(s):  
Middle Miocene ◽  
Carbon Fixation ◽  
Middle Eocene ◽  
Ice Sheet ◽  
Algal Growth ◽  
Equatorial Atlantic ◽  
Antarctic Ice Sheet ◽  
The Past ◽  
Wide Range

The alkenone– p CO 2 methodology has been used to reconstruct the partial pressure of ancient atmospheric carbon dioxide ( p CO 2 ) for the past 45 million years of Earth's history (Middle Eocene to Pleistocene epochs). The present long-term CO 2 record is a composite of data from multiple ocean localities that express a wide range of oceanographic and algal growth conditions that potentially bias CO 2 results. In this study, we present a p CO 2 record spanning the past 40 million years from a single marine locality, Ocean Drilling Program Site 925 located in the western equatorial Atlantic Ocean. The trends and absolute values of our new CO 2 record site are broadly consistent with previously published multi-site alkenone–CO 2 results. However, new p CO 2 estimates for the Middle Miocene are notably higher than published records, with average p CO 2 concentrations in the range of 400–500 ppm. Our results are generally consistent with recent p CO 2 estimates based on boron isotope-pH data and stomatal index records, and suggest that CO 2 levels were highest during a period of global warmth associated with the Middle Miocene Climatic Optimum (17–14 million years ago, Ma), followed by a decline in CO 2 during the Middle Miocene Climate Transition (approx. 14 Ma). Several relationships remain contrary to expectations. For example, benthic foraminiferal δ 18 O records suggest a period of deglaciation and/or high-latitude warming during the latest Oligocene (27–23 Ma) that, based on our results, occurred concurrently with a long-term decrease in CO 2 levels. Additionally, a large positive δ 18 O excursion near the Oligocene–Miocene boundary (the Mi-1 event, approx. 23 Ma), assumed to represent a period of glacial advance and retreat on Antarctica, is difficult to explain by our CO 2 record alone given what is known of Antarctic ice sheet history and the strong hysteresis of the East Antarctic Ice Sheet once it has grown to continental dimensions. We also demonstrate that in the Neogene with low CO 2 levels, algal carbon concentrating mechanisms and spontaneous biocarbonate–CO 2 conversions are likely to play a more important role in algal carbon fixation, which provides a potential bias to the alkenone– p CO 2 method.

Application of A Monte Carlo Approach to Surface Complexation Modelling

2004 ◽  
Vol 824 ◽  
Author(s):  
M.M. Askarieh ◽  
T.G. Heath ◽  
W.M. Tearle
Keyword(s):  
Monte Carlo ◽  
Model Parameters ◽  
Surface Complexes ◽  
Monte Carlo Approach ◽  
Ion Sorption ◽  
Wide Range ◽  
Complex Models ◽  
Chemical Conditions ◽  
Parameter Values

AbstractA Monte Carlo-based approach has been adopted for development of a chemical thermodynamic model to describe the goethite surface in contact with sodium nitrate solutions. The technique involves the calculation of the goethite surface properties for the chemical conditions corresponding to each experimental data point. The representation of the surface was based on a set of model parameters, each of which was either fixed or was randomly sampled from a specified range of values. Thousands of such model representations were generated for different selected sets of parameter values with the use of the standard geochemical speciation computer program, HARPHRQ. The method allowed many combinations of parameter values to be sampled that might not be achieved with a simple least-squares fitting approach. It also allowed the dependence of the quality of fit on each parameter to be analysed. The Monte Carlo approach is most appropriate in the development of complex models involving the fitting of several datasets with several fitting parameters.Introduction of selenate surface complexes allowed the model to be extended to represent selenate ion sorption, selenium being an important radioelement in evaluation of the long-term safety of ILW disposal. The sorption model gave good agreement with a wide range of experimental sorption datasets for selenate.

scholarly journals Model-based detection and analysis of introgressed Neanderthal ancestry in modern humans

2017 ◽  
Author(s):  
Matthias Steinrücken ◽  
Jeffrey P. Spence ◽  
John A. Kamm ◽  
Emilia Wieczorek ◽  
Yun S. Song
Keyword(s):  
Genetic Material ◽  
Genetic Load ◽  
Modern Human ◽  
Human Populations ◽  
Effective Population ◽  
Weak Selection ◽  
Modern Humans ◽  
High Coverage ◽  
Model Based ◽  
And Migration

AbstractGenetic evidence has revealed that the ancestors of modern human populations outside of Africa and their hominin sister groups, notably the Neanderthals, exchanged genetic material in the past. The distribution of these introgressed sequence-tracts along modern-day human genomes provides insight into the ancient structure and migration patterns of these archaic populations. Furthermore, it facilitates studying the selective processes that lead to the accumulation or depletion of introgressed genetic variation. Recent studies have developed methods to localize these introgressed regions, reporting long regions that are depleted of Neanderthal introgression and enriched in genes, suggesting negative selection against the Neanderthal variants. On the other hand, enriched Neanderthal ancestry in hair- and skin-related genes suggests that some introgressed variants facilitated adaptation to new environments. Here, we present a model-based method called diCal-admix and apply it to detect tracts of Neanderthal introgression in modern humans. We demonstrate its efficiency and accuracy through extensive simulations. We use our method to detect introgressed regions in modern human individuals from the 1000 Genomes Project, using a high coverage genome from a Neanderthal individual from the Altai mountains as reference. Our introgression detection results and findings concerning their functional implications are largely concordant with previous studies, and are consistent with weak selection against Neanderthal ancestry. We find some evidence that selection against Neanderthal ancestry was due to higher genetic load in Neanderthals, resulting from small effective population size, rather than Dobzhansky-Müller incompatibilities. Finally, we investigate the role of the X-chromosome in the divergence between Neanderthals and modern humans.

scholarly journals Archaic mitochondrial DNA inserts in modern day nuclear genomes

2019 ◽  
Author(s):  
Robert Bücking ◽  
Murray P Cox ◽  
Georgi Hudjashov ◽  
Lauri Saag ◽  
Herawati Sudoyo ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Nuclear Dna ◽  
Modern Human ◽  
Next Generation Sequencing Data ◽  
Human Populations ◽  
Sequencing Data ◽  
Modern Humans ◽  
High Coverage ◽  
Nuclear Genomes ◽  
Generation Sequencing

Abstract Background: Traces of interbreeding of Neanderthals and Denisovans with modern humans in the form of archaic DNA have been detected in the genomes of present-day human populations outside sub-Sahara Africa. Up to now, only nuclear archaic DNA has been detected in modern humans; we therefore attempted to identify archaic mitochondrial DNA (mtDNA) residing in modern human nuclear genomes as nuclear inserts of mitochondrial DNA (NUMTs). Results: We analysed 221 high-coverage genomes from Oceania and Indonesia using an approach which identifies reads that map both to the nuclear and mitochondrial DNA. We then classified reads according to the source of the mtDNA, and found one NUMT of Denisovan mtDNA origin; analysis of the flanking region suggests that this insertion is more likely to have happened in a Denisovan individual and introgressed into modern humans with the Denisovan nuclear DNA, rather than in a descendant of a Denisovan female and a modern human male. Conclusions: Here we present our pipeline for detecting introgressed NUMTs in next generation sequencing data that can be used on genomes sequenced in the future. Further discovery of such archaic NUMTs in modern humans can be used to detect interbreeding between archaic and modern humans and can reveal new insights into the nature of such interbreeding events.

scholarly journals Effect of partial selfing and polygenic selection on establishment in a new habitat

2019 ◽  
Author(s):  
Himani Sachdeva
Keyword(s):  
Inbreeding Depression ◽  
Evolutionary Dynamics ◽  
High Rate ◽  
Source Population ◽  
Selfing Rate ◽  
Deleterious Alleles ◽  
Wide Range ◽  
Mate Limitation ◽  
Polygenic Selection

AbstractThis paper analyzes how partial selfing in a large source population influences its ability to colonize a new habitat via the introduction of a few founder individuals. Founders experience inbreeding depression due to partially recessive deleterious alleles as well as maladaptation to the new environment due to selection on a large number of additive loci. I first introduce a simplified version of the Inbreeding History Model (Kelly, 2007) in order to characterize mutation-selection balance in a large, partially selfing source population under selection involving multiple non-identical loci. I then use individual-based simulations to study the eco-evolutionary dynamics of founders establishing in the new habitat under a model of hard selection. The study explores how selfing rate shapes establishment probabilities of founders via effects on both inbreeding depression and adaptability to the new environment, and also distinguishes the effects of selfing on the initial fitness of founders from its effects on the long-term adaptive response of the populations they found. A high rate of (but not complete) selfing is found to aid establishment over a wide range of parameters, even in the absence of mate limitation. The sensitivity of the results to assumptions about the nature of polygenic selection are discussed.

scholarly journals Archaic mitochondrial DNA inserts in modern day nuclear genomes

2019 ◽  
Author(s):  
Robert Bücking ◽  
Murray P Cox ◽  
Georgi Hudjashov ◽  
Lauri Saag ◽  
Herawati Sudoyo ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Nuclear Dna ◽  
Modern Human ◽  
Next Generation Sequencing Data ◽  
Human Populations ◽  
Sequencing Data ◽  
Modern Humans ◽  
High Coverage ◽  
Nuclear Genomes ◽  
Generation Sequencing

Abstract Background Traces of interbreeding of Neanderthals and Denisovans with modern humans in the form of archaic DNA have been detected in the genomes of present-day human populations outside sub-Sahara Africa. Up to now, only nuclear archaic DNA has been detected in modern humans; we therefore attempted to identify archaic mitochondrial DNA (mtDNA) residing in modern human nuclear genomes as nuclear inserts of mitochondrial DNA (NUMTs). Results We analysed 221 high-coverage genomes from Oceania and Indonesia using an approach which identifies reads that map both to the nuclear and mitochondrial DNA. We then classified reads according to the source of the mtDNA, and found one NUMT of Denisovan mtDNA origin; analysis of the flanking region suggests that this insertion is more likely to have happened in a Denisovan individual and introgressed into modern humans with the Denisovan nuclear DNA, rather than in a descendant of a Denisovan female and a modern human male. Conclusions Here we present our pipeline for detecting introgressed NUMTs in next generation sequencing data that can be used on genomes sequenced in the future. Further discovery of such archaic NUMTs in modern humans can be used to detect interbreeding between archaic and modern humans and can reveal new insights into the nature of such interbreeding events.

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