Dating Tips for Divergence-Time Estimation

The molecular clock is the only viable means of establishing an accurate timescale for Life on Earth, but it remains reliant on a capricious fossil record for calibration. 'Tip-dating' promises a conceptual advance, integrating fossil species among their living relatives using molecular/morphological datasets and evolutionary models. Fossil species of known age establish calibration directly, and their phylogenetic uncertainty is accommodated through the co-estimation of time and topology. However, challenges remain, including a dearth of effective models of morphological evolution, rate correlation, the non-random nature of missing characters in fossil data, and, most importantly, accommodating uncertainty in fossil age. We show uncertainty in fossil-dating propagates to divergence-time estimates, yielding estimates that are older and less precise than those based on traditional node calibration. Ultimately, node and tip calibrations are not mutually incompatible and may be integrated to achieve more accurate and precise evolutionary timescales. Total evidence dating constitutes a significant advance in divergence-time estimation. It overcomes problems with calibration by including fossil species on a par with their living relatives, using molecular sequence data from living species supplemented by morphological data from both living and fossil species. The method relies on the controversial hypothesis of a morphological clock and suffers from the lack of development of realistic models of morphological evolution. Most studies have failed to accommodate fossil age uncertainty. We present a protocol for characterizing and implementing this uncertainty, and demonstrate its impact on divergence-time estimation. We argue that total evidence dating encompasses a suite of methods that can be used in bespoke combinations chosen to best suit the nature of specific divergence-time estimation studies.</p

A Mutation-Selection Model of Protein Evolution under Persistent Positive Selection

We use first principles of population genetics to model the evolution of proteins under persistent positive selection (PPS). PPS may occur when organisms are subjected to persistent environmental change, during adaptive radiations, or in host-pathogen interactions. Our mutation-selection model indicates protein evolution under PPS is an irreversible Markov process, and thus proteins under PPS show a strongly asymmetrical distribution of selection coefficients among amino acid substitutions. Our model shows the criteria ω>1 (where ω is the ratio of nonsynonymous over synonymous codon substitution rates) to detect positive selection is conservative and indeed arbitrary, because in real proteins many mutations are highly deleterious and are removed by selection even at positively selected sites. We use a penalized-likelihood implementation of the PPS model to successfully detect PPS in plant RuBisCO and influenza HA proteins. By directly estimating selection coefficients at protein sites, our inference procedure bypasses the need for using ω as a surrogate measure of selection and improves our ability to detect molecular adaptation in proteins

Spin crossover transition driven by pressure: Barocaloric applications

This article describes a mean-field theoretical model for Spin-Crossover (SCO) materials and explores its implications. It is based on a simple Hamiltonian that yields the high spin molar fraction as a function of temperature and pressure, as well as a temperature-pressure phase diagram for the SCO transition. In order to test the model, we apply it to the giant Barocaloric Effect (BCE) of the SCO material [FeL$_2$][BF$_4$]$_2$ and comprehensively analyse its behavior. We found that optical phonons are responsible for 92\% of the total barocaloric entropy change. DFT calculations show that these optical phonons are mainly assigned to the low frequencies modes of vibration ($<400$ cm$^{-1}$), being associated to the Fe coordination.Comment: 6 figure

Finding Direction in the Search for Selection.

Tests for positive selection have mostly been developed to look for diversifying selection where change away from the current amino acid is often favorable. However, in many cases we are interested in directional selection where there is a shift toward specific amino acids, resulting in increased fitness in the species. Recently, a few methods have been developed to detect and characterize directional selection on a molecular level. Using the results of evolutionary simulations as well as HIV drug resistance data as models of directional selection, we compare two such methods with each other, as well as against a standard method for detecting diversifying selection. We find that the method to detect diversifying selection also detects directional selection under certain conditions. One method developed for detecting directional selection is powerful and accurate for a wide range of conditions, while the other can generate an excessive number of false positives

Gradual strenuous running regimen predisposes to osteoarthritis due to cartilage cell death and altered levels of glycosaminoglycans

Objective: To investigate the hypothesis that strenuous running is a predisposing factor for osteoarthritis.Design: Wistar rats were divided into two groups: a control group (CG) and a trained group (TG). the TG underwent a strenuous treadmill running training regimen of controlled intensity, exhibiting progressively improvement of fitness over 12 weeks, running at least 55 km during this period and finally performing an ultra-endurance running exercise to exhaustion. After this period, rats from both groups were euthanized and their knees removed. the articular cartilage was dissected and submitted to histomorphometrical, histomorphological, and immunohistochemical analyses evaluating cell death pathway (caspase-3 and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick 'end labeling (TUNEL)) and inflammatory cytokines [interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha)]. in addition, the tissues were analyzed regarding the types and the content of glycosaminoglycans.Results: the TG knee joints exhibited increase in the number of chondrocytes and chondrocyte clusters, as well as significantly increased levels of caspase-3, a protein involved in apoptosis, and of inflammatory cytokines IL-1 alpha and TNF-alpha. in addition, histologically higher grades of osteoarthritis (Osteoarthritis Research Society International - OARSI grading), and significantly decreased levels of chondroitin sulfate and hyaluronic acid. Knee cartilage thickness and TUNEL did not significantly differ between the two groups.Conclusions: the articular cartilage of rats subjected to a strenuous running regimen of controlled intensity exhibited molecular and histological characteristics that are present in osteoarthritis. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Escola Paulista Med, Dept Orthopaed & Traumatol, BR-04038032 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Morphol & Genet, BR-04038032 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Program Mol Biol, BR-04038032 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Orthopaed & Traumatol, BR-04038032 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Morphol & Genet, BR-04038032 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Program Mol Biol, BR-04038032 São Paulo, BrazilWeb of Scienc

RelTime Rates Collapse to a Strict Clock When Estimating the Timeline of Animal Diversification

© The Author 2017.Establishing an accurate timescale for the history of life is crucial to understand evolutionary processes. For this purpose, relaxed molecular clock models implemented in a Bayesian MCMC framework are generally used. However, these methods are time consuming. RelTime, a non-Bayesian method implementing a fast, ad hoc, algorithm for relative dating, was developed to overcome the computational inefficiencies of Bayesian software. RelTime was recently used to investigate the timing of origin of animals, yielding results consistent with early strict clock studies from the 1980s and 1990s, estimating metazoans to have a Mesoproterozoic origin—over a billion years ago. RelTime results are unexpected and disagree with the largest majority of modern, relaxed, Bayesian molecular clock analyses, which suggest animals originated in the Tonian-Cryogenian (less that 850 million years ago). Here, we demonstrate that RelTime-inferred divergence times for the origin of animals are spurious, a consequence of the inability of RelTime to relax the clock along the internal branches of the animal phylogeny. RelTime-inferred divergence times are comparable to strict-clock estimates because they are essentially inferred under a strict clock. Our results warn us of the danger of using ad hoc algorithms making implicit assumptions about rate changes along a tree. Our study roundly rejects a Mesoproterozoic origin of animals; metazoans emerged in the Tonian-Cryogenian, and diversified in the Ediacaran, in the immediate prelude to the routine fossilization of animals in the Cambrian associated with the emergence of readily preserved skeletons.This research was funded by a Marie Skłodowska-Curie Fellowship (655814 to J.L.-F.), grants from the NERC BETR (NE/P013643/1 to D.P. and P.C.J.D.), BBSRC (BB/N000919/1 to P.C.J.D.), John Templeton Foundation 43915 (D.P.) and a Royal Society Wolfson Research Merit Award (P.C.J.D.).Peer reviewe

Nucleotide usage biases distort inferences of the species tree

This work was supported by the Vienna Science and Technology Fund (WWTF) [MA16-061] and partially supported by the Austrian Science Fund (FWF) [P34524-B]. GJS received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation program under grant agreement no. 714774 and the grant GINOP-2.3.2.-15-2016-00057.Despite the importance of natural selection in species' evolutionary history, phylogenetic methods that take into account population-level processes typically ignore selection. The assumption of neutrality is often based on the idea that selection occurs at a minority of loci in the genome and is unlikely to compromise phylogenetic inferences significantly. However, genome-wide processes like GC-bias and some variation segregating at the coding regions are known to evolve in the nearly neutral range. As we are now using genome-wide data to estimate species trees, it is natural to ask whether weak but pervasive selection is likely to blur species tree inferences. We developed a polymorphism-aware phylogenetic model tailored for measuring signatures of nucleotide usage biases to test the impact of selection in the species tree. Our analyses indicate that while the inferred relationships among species are not significantly compromised, the genetic distances are systematically underestimated in a node-height dependent manner: i.e., the deeper nodes tend to be more underestimated than the shallow ones. Such biases have implications for molecular dating. We dated the evolutionary history of 30 worldwide fruit fly populations, and we found signatures of GC-bias considerably affecting the estimated divergence times (up to 23%) in the neutral model. Our findings call for the need to account for selection when quantifying divergence or dating species evolution.Publisher PDFPeer reviewe

Relação entre a presença de Escherichia coli e Trueperella pyogenes no fundo vaginal e o desempenho reprodutivo de vacas leiteiras mestiças

Trabalho de Conclusão de Curso (Graduação)Com o presente estudo objetivou-se identificar cepas bacterianas presentes em fundo vaginal de vacas leiteiras na primeira semana pós-parto e avaliar a relação entre a presença das bacterias bacterias Escherichia coli e Trueperella pyogenes e o intervalo parto primeira inseminação, parto concepção e porcentagem de vacas gestantes até 365 dias após o parto. Amostras da secreção presente no fundo vaginal de 33 vacas na primeira semana após o parto foram coletadas e analisadas bacteriologicamente através da técnica de isolamento. Das 33 amostras coletadas, 31 delas apresentaram crescimento bacteriano com 25 espécies diferentes de bactérias. As duas espécies bacterianas, Escherichia coli e Trueperella pyogenes, relatadas como agente de infecção uterina, foram detectadas em 84% das amostras. As vacas com mais de 45 dias pós-parto, foram submetidas a um protocolo de inseminação artificial em tempo fixo (IATF) a base de estradiol e progesterona. Após 32 dias da IATF foi realizado o diagnóstico de gestação por exame de ultrassonografia. As vacas vazias foram submetidas novamente ao protocolo de IATF, até ficarem gestantes ou encerrarem a lactação. Foram analizados o intervalo entre parto e a primeira IATF, o intervalo parto concepção, a integridade vulvar e presença de doenças no trato reprodutivo bem como as taxas de prenhez dos animais até 365 dias pós-parto. A presença de Escherichia coli, Trueperella pyogenes ou ambas no fundo vaginal de vacas na primeira semana pós-parto aumentou o intervalo parto primeira inseminação de 64 para 101,67 dias, bem como o intervalo parto concepção em até 81,33 para 143,50 dias, além de diminuir a porcentagem de vacas gestantes ao longo da lactação de 75 % para 0,00%. Conclui-se que a presença de bactérias em fundo vaginal no pós-parto afeta a eficiência reprodutiva de vacas leiteiras

Comparison of different strategies for using fossil calibrations to generate the time prior in Bayesian molecular clock dating.

Fossil calibrations are the utmost source of information for resolving the distances between molecular sequences into estimates of absolute times and absolute rates in molecular clock dating analysis. The quality of calibrations is thus expected to have a major impact on divergence time estimates even if a huge amount of molecular data is available. In Bayesian molecular clock dating, fossil calibration information is incorporated in the analysis through the prior on divergence times (the time prior). Here, we evaluate three strategies for converting fossil calibrations (in the form of minimum- and maximum-age bounds) into the prior on times, which differ according to whether they borrow information from the maximum age of ancestral nodes and minimum age of descendent nodes to form constraints for any given node on the phylogeny. We study a simple example that is analytically tractable, and analyze two real datasets (one of 10 primate species and another of 48 seed plant species) using three Bayesian dating programs: MCMCTree, MrBayes and BEAST2. We examine how different calibration strategies, the birth-death process, and automatic truncation (to enforce the constraint that ancestral nodes are older than descendent nodes) interact to determine the time prior. In general, truncation has a great impact on calibrations so that the effective priors on the calibration node ages after the truncation can be very different from the user-specified calibration densities. The different strategies for generating the effective prior also had considerable impact, leading to very different marginal effective priors. Arbitrary parameters used to implement minimum-bound calibrations were found to have a strong impact upon the prior and posterior of the divergence times. Our results highlight the importance of inspecting the joint time prior used by the dating program before any Bayesian dating analysis.This research was funded by Biotechnology and Biosciences Research Council (UK) grant (BB/N000609/1) and Natural Environment Research Council (UK) grant (NE/N002067/1). J.B.-M. was supported by a CONACyT-Mexico and UCL scholarship

Bayesian molecular clock dating of species divergences in the genomics era

It has been five decades since the proposal of the molecular clock hypothesis, which states that the rate of evolution at the molecular level is constant through time and among species. This hypothesis has become a powerful tool in evolutionary biology, making it possible to use molecular sequences to estimate the geological ages of species divergence events. With recent advances in Bayesian clock dating methodology and the explosive accumulation of genetic sequence data, molecular clock dating has found widespread applications, from tracking virus pandemics, to studying the macroevolutionary process of speciation and extinction, to estimating a timescale for Life on Earth