scholarly journals Statistics used to infer inter-breeding between humans and Neanderthals are strongly predicted by flanking sequence heterozygosity

2020 ◽  
Author(s):  
William Amos
Keyword(s):  
Mutation Rate ◽  
Common Ancestor ◽  
Ancestral Sequence ◽  
Flanking Sequence ◽  
New Model ◽  
Immune Genes ◽  
Strong Selection ◽  
Potent Predictor ◽  
False Assumption

AbstractA large and rapidly expanding literature has grown out of the observation that humans carry a genetic legacy reflecting ancient inter-breeding with archaic hominins such as Neanderthals and Denisovans. However, a recent study suggests that a commonly used statistic used to assess legacy size, D, is driven mainly by heterozygous sites in Africa acting to increase divergence from our common ancestor rather than introgressed fragments outside Africa reducing divergence. To test this new model, I analysed how D is influenced by heterozygosity within a kilobase of each putative introgressed base. I find that flanking heterozygosity is a potent predictor of D, with introgression always being inferred as having occurred into the population with lower heterozygosity. This pattern cannot be driven by any introgressed fragments themselves, which simulations show create the exact converse pattern, but instead appears to be generated by heterozygosity acting to drive increased divergence from the ancestral sequence. This new model explains why introgression of haploid or semi-haploid regions is essentially lacking and why introgression is often inferred around immune genes and other regions under strong selection. More generally, these results raise the possibility that reported legacies are largely an artefact arising out of the false assumption that mutation rate is constant.

scholarly journals FHJ: A formal model for hierarchical dispatching and overriding

2020 ◽  
Author(s):  
Y Wang ◽  
H Zhang ◽  
BCDS Oliveira ◽  
Marco Servetto
Keyword(s):  
Common Ancestor ◽  
Formal Model ◽  
Object Oriented ◽  
Object Oriented Programming ◽  
Extensive Literature ◽  
Multiple Inheritance ◽  
New Model ◽  
Dynamic Type ◽  
Inheritance Hierarchy ◽  
Type Information

© Yanlin Wang, Haoyuan Zhang, Bruno C. d. S. Oliveira, and Marco Servetto. Multiple inheritance is a valuable feature for Object-Oriented Programming. However, it is also tricky to get right, as illustrated by the extensive literature on the topic. A key issue is the ambiguity arising from inheriting multiple parents, which can have conflicting methods. Numerous existing work provides solutions for conflicts which arise from diamond inheritance: i.e. conflicts that arise from implementations sharing a common ancestor. However, most mechanisms are inadequate to deal with unintentional method conflicts: conflicts which arise from two unrelated methods that happen to share the same name and signature. This paper presents a new model called Featherweight Hierarchical Java (FHJ) that deals with unintentional method conflicts. In our new model, which is partly inspired by C++, conflicting methods arising from unrelated methods can coexist in the same class, and hierarchical dispatching supports unambiguous lookups in the presence of such conflicting methods. To avoid ambiguity, hierarchical information is employed in method dispatching, which uses a combination of static and dynamic type information to choose the implementation of a method at run-time. Furthermore, unlike all existing inheritance models, our model supports hierarchical method overriding: that is, methods can be independently overridden along the multiple inheritance hierarchy. We give illustrative examples of our language and features and formalize FHJ as a minimal Featherweight-Java style calculus.

scholarly journals A model of mutation appropriate to estimate the number of electrophoretically detectable alleles in a finite population

1973 ◽  
Vol 22 (2) ◽  
pp. 201-204 ◽  
Author(s):  
Tomoko Ohta ◽  
Motoo Kimura
Keyword(s):  
Mutation Rate ◽  
Finite Population ◽  
Effective Size ◽  
Effective Number ◽  
Positive Direction ◽  
New Model ◽  
Negative Direction ◽  
One Step ◽  
Image Position

SUMMARYA new model of mutational production of alleles was proposed which may be appropriate to estimate the number of electrophoretically detectable alleles maintained in a finite population. The model assumes that the entire allelic states are expressed by integers (…, A−1, A0, A1, …) and that if an allele changes state by mutation the change occurs in such a way that it moves either one step in the positive direction or one step in the negative direction (see also Fig. 1). It was shown that for this model the ‘effective’ number of selectively neutral alleles maintained in a population of the effective size Ne under mutation rate υ per generation is given byWhen 4Neυ is small, this differs little from the conventional formula by Kimura & Crow, i.e. ne = 1 + 4Neυ, but it gives a much smaller estimate than this when 4Neυ is large.

scholarly journals The quantity of Neanderthal DNA in modern humans: a reanalysis relaxing the assumption of constant mutation rate

2016 ◽  
Author(s):  
William Amos
Keyword(s):  
Mutation Rate ◽  
Common Ancestor ◽  
Alternative Hypothesis ◽  
Large Contribution ◽  
Modern Humans ◽  
Out Of Africa ◽  
Loss Of Diversity ◽  
Induced Changes

AbstractFew now dispute that a few percent of the DNA of non-African humans is a legacy of interbreeding with Neanderthals. However, heterozygosity and mutation rate appear to be linked such that the loss of diversity associated with humans migrating out of Africa caused a mutational slowdown, allowing Africans to diverge more from both our common ancestor and Neanderthals. Here I use a range of contrasting tests aimed at distinguishing between mutation slowdown and introgression as explanations for the higher rates of base-sharing between non-Africans and Neanderthals. In every instance the mutation slowdown hypothesis fits better. Thus, while some interbreeding likely occurred, as evidenced by the finding of skeletons of admixed individuals, adaptive genes and the apparently large contribution of Denisovan DNA to Oceanian genomes, my results challenge the idea that non-Africans generally carry an appreciable Neanderthal legacy. My analysis shows that inferences about introgression may be unreliable unless variation in mutation rate linked to demographically induced changes in heterozygosity can be excluded as an alternative hypothesis.

scholarly journals Response to Comment on “Ancient origins of allosteric activation in a Ser-Thr kinase”

Science ◽  
2020 ◽  
Vol 370 (6519) ◽  
pp. eabd0364
Author(s):  
Christopher Wilson ◽  
Dorothee Kern
Keyword(s):  
Common Ancestor ◽  
Species Tree ◽  
Ancestral Sequence ◽  
Gene Trees ◽  
Allosteric Activation ◽  
Ancestral Sequence Reconstruction ◽  
Sequence Reconstruction

Park et al. question one out of seven findings from Hadzipasic et al.: whether TPX2 allosterically regulates the oldest Aurora. We had already addressed the two concerns raised—sparse sequence sampling and not forcing the gene to the species tree—before publication. Moreover, we believe their ancestral sequence reconstruction would be consistent with a nonallosteric common ancestor, and we show large sequence differences caused by species tree–enforced gene trees.

scholarly journals The molecular signal for the adaptation to cold temperature during early life on Earth

2013 ◽  
Vol 9 (5) ◽  
pp. 20130608 ◽  
Author(s):  
Mathieu Groussin ◽  
Bastien Boussau ◽  
Sandrine Charles ◽  
Samuel Blanquart ◽  
Manolo Gouy
Keyword(s):  
Phylogenetic Trees ◽  
Large Scale ◽  
Common Ancestor ◽  
Phylogenetic Signal ◽  
Optimal Growth ◽  
Ancestral Sequence ◽  
Rate Variation ◽  
Last Common Ancestor ◽  
Ancestral Sequence Reconstruction ◽  
Sequence Reconstruction

Several lines of evidence such as the basal location of thermophilic lineages in large-scale phylogenetic trees and the ancestral sequence reconstruction of single enzymes or large protein concatenations support the conclusion that the ancestors of the bacterial and archaeal domains were thermophilic organisms which were adapted to hot environments during the early stages of the Earth. A parsimonious reasoning would therefore suggest that the last universal common ancestor (LUCA) was also thermophilic. Various authors have used branch-wise non-homogeneous evolutionary models that better capture the variation of molecular compositions among lineages to accurately reconstruct the ancestral G + C contents of ribosomal RNAs and the ancestral amino acid composition of highly conserved proteins. They confirmed the thermophilic nature of the ancestors of Bacteria and Archaea but concluded that LUCA, their last common ancestor, was a mesophilic organism having a moderate optimal growth temperature. In this letter, we investigate the unknown nature of the phylogenetic signal that informs ancestral sequence reconstruction to support this non-parsimonious scenario. We find that rate variation across sites of molecular sequences provides information at different time scales by recording the oldest adaptation to temperature in slow-evolving regions and subsequent adaptations in fast-evolving ones.

scholarly journals Large-Scale Comparative Analysis of Codon Models Accounting for Protein and Nucleotide Selection

2017 ◽  
Author(s):  
Iakov I. Davydov ◽  
Nicolas Salamin ◽  
Marc Robinson-Rechavi
Keyword(s):  
Positive Selection ◽  
Mutation Rate ◽  
Substitution Rate ◽  
Large Scale ◽  
Synonymous Substitution ◽  
Rate Variation ◽  
New Model ◽  
Codon Models ◽  
Substitution Rate Variation ◽  
Mutation Rate Variation

AbstractThere are numerous sources of variation in the rate of synonymous substitutions inside genes, such as direct selection on the nucleotide sequence, or mutation rate variation. Yet scans for positive selection rely on codon models which incorporate an assumption of effectively neutral synonymous substitution rate, constant between sites of each gene. Here we perform a large-scale comparison of approaches which incorporate codon substitution rate variation and propose our own simple yet effective modification of existing models. We find strong effects of substitution rate variation on positive selection inference. More than 70% of the genes detected by the classical branch-site model are presumably false positives caused by the incorrect assumption of uniform synonymous substitution rate. We propose a new model which is strongly favored by the data while remaining computationally tractable. With the new model we can capture signatures of nucleotide level selection acting on translation initiation and on splicing sites within the coding region. Finally, we show that rate variation is highest in the highly recombining regions, and we propose that recombination and mutation rate variation, such as high CpG mutation rate, are the two main sources of nucleotide rate variation. While we detect fewer genes under positive selection in Drosophila than without rate variation, the genes which we detect contain a stronger signal of adaptation of dynein, which could be associated with Wolbachia infection. We provide software to perform positive selection analysis using the new model.

scholarly journals FHJ: A formal model for hierarchical dispatching and overriding

2020 ◽  
Author(s):  
Y Wang ◽  
H Zhang ◽  
BCDS Oliveira ◽  
Marco Servetto
Keyword(s):  
Common Ancestor ◽  
Formal Model ◽  
Object Oriented ◽  
Object Oriented Programming ◽  
Extensive Literature ◽  
Multiple Inheritance ◽  
New Model ◽  
Dynamic Type ◽  
Inheritance Hierarchy ◽  
Type Information

© Yanlin Wang, Haoyuan Zhang, Bruno C. d. S. Oliveira, and Marco Servetto. Multiple inheritance is a valuable feature for Object-Oriented Programming. However, it is also tricky to get right, as illustrated by the extensive literature on the topic. A key issue is the ambiguity arising from inheriting multiple parents, which can have conflicting methods. Numerous existing work provides solutions for conflicts which arise from diamond inheritance: i.e. conflicts that arise from implementations sharing a common ancestor. However, most mechanisms are inadequate to deal with unintentional method conflicts: conflicts which arise from two unrelated methods that happen to share the same name and signature. This paper presents a new model called Featherweight Hierarchical Java (FHJ) that deals with unintentional method conflicts. In our new model, which is partly inspired by C++, conflicting methods arising from unrelated methods can coexist in the same class, and hierarchical dispatching supports unambiguous lookups in the presence of such conflicting methods. To avoid ambiguity, hierarchical information is employed in method dispatching, which uses a combination of static and dynamic type information to choose the implementation of a method at run-time. Furthermore, unlike all existing inheritance models, our model supports hierarchical method overriding: that is, methods can be independently overridden along the multiple inheritance hierarchy. We give illustrative examples of our language and features and formalize FHJ as a minimal Featherweight-Java style calculus.

scholarly journals Enabling inference for context-dependent models of mutation by bounding the propagation of dependency

2021 ◽  
Author(s):  
Erick Matsen ◽  
Peter L. Ralph
Keyword(s):  
Bayesian Inference ◽  
Maximum Likelihood ◽  
Common Ancestor ◽  
Phylogenetic Inference ◽  
R Package ◽  
Flanking Sequence ◽  
Model Refinement ◽  
Iterative Model ◽  
The Common ◽  
Context Dependent

Although the rates at which positions in the genome mutate are known to depend not only on the nucleotide to be mutated, but also on neighboring nucleotides, it remains challenging to do phylogenetic inference using models of context-dependent mutation. In these models, the effects of one mutation may in principle propagate to faraway locations, making it difficult to compute exact likelihoods. This paper shows how to use bounds on the propagation of dependency to compute likelihoods of mutation of a given segment of genome by marginalizing over sufficiently long flanking sequence. This can be used for maximum likelihood or Bayesian inference. Protocols examining residuals and iterative model refinement are also discussed. Tools for efficiently working with these models are provided in an R package, that could be used in other applications. The method is used to examine context dependence of mutations since the common ancestor of humans and chimpanzee.

scholarly journals A new model of human dispersal

2015 ◽  
Author(s):  
Trevor G Underwood
Keyword(s):  
Common Ancestor ◽  
New Model ◽  
Human Dispersal ◽  
Eurasian Lineage ◽  
Phylogenetic Model ◽  
Admixed Population ◽  
The Common ◽  
Out Of Africa ◽  
Sub Saharan ◽  
Mtdna Haplogroup

Analysis of previously unpublished allele counts obtained from the French-San-Neanderthal-Chimpanzee alignment of the high quality DNA sequence of a Neanderthal from the Altai Mountains raises significant questions about the currently accepted phylogenetic model of the origins of Europeans. Previous estimates of the proportion of Neanderthal ancestry in present-day Europeans ranged between 1.3% and 2.7% supporting a recent Out-of Africa dispersal model followed by a low level of admixture with Neanderthals. However, analysis of the allele counts indicates the existence of an unidentified third archaic ancestor of Europeans, which diverged from its common ancestor with sub-Saharan Africans around 900 thousand years ago. This analysis shows that the relative proportions of derived alleles in the 0.0826% of the European genome that is not shared with the common ancestor of humans and chimpanzee are 13.6% Neanderthal, 32.3% sub-Saharan African and 54.2% third archaic ancestor. This analysis together with anthropological and archaeological evidence suggests a new model of human dispersal based on a Eurasian lineage in the Levant, which admixed with Neanderthals and descendants of African mtDNA haplogroup L3, followed by radiation from a basal admixed population around 55-50 Kya, with no subsequent major contribution to the European genome.

The Hitachi Model HS-8 Electron Microscope

1967 ◽  
Vol 25 ◽  
pp. 238-239
Author(s):  
H. Akabori ◽  
K. Nishiwaki ◽  
K. Yoneta
Keyword(s):  
Electron Microscope ◽  
New Model ◽  
Predecessor Model

By improving the predecessor Model HS- 7 electron microscope for the purpose of easier operation, we have recently completed new Model HS-8 electron microscope featuring higher performance and ease of operation.

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