ResearchPad - evolutionary-rate https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Assessing the accuracy of phylogenetic rooting methods on prokaryotic gene families]]> https://www.researchpad.co/article/elastic_article_14731 Almost all standard phylogenetic methods for reconstructing gene trees result in unrooted trees; yet, many of the most useful applications of gene trees require that the gene trees be correctly rooted. As a result, several computational methods have been developed for inferring the root of unrooted gene trees. However, the accuracy of such methods has never been systematically evaluated on prokaryotic gene families, where horizontal gene transfer is often one of the dominant evolutionary events driving gene family evolution. In this work, we address this gap by conducting a thorough comparative evaluation of five different rooting methods using large collections of both simulated and empirical prokaryotic gene trees. Our simulation study is based on 6000 true and reconstructed gene trees on 100 species and characterizes the rooting accuracy of the four methods under 36 different evolutionary conditions and 3 levels of gene tree reconstruction error. The empirical study is based on a large, carefully designed data set of 3098 gene trees from 504 bacterial species (406 Alphaproteobacteria and 98 Cyanobacteria) and reveals insights that supplement those gleaned from the simulation study. Overall, this work provides several valuable insights into the accuracy of the considered methods that will help inform the choice of rooting methods to use when studying microbial gene family evolution. Among other findings, this study identifies parsimonious Duplication-Transfer-Loss (DTL) rooting and Minimal Ancestor Deviation (MAD) rooting as two of the most accurate gene tree rooting methods for prokaryotes and specifies the evolutionary conditions under which these methods are most accurate, demonstrates that DTL rooting is highly sensitive to high evolutionary rates and gene tree error, and that rooting methods based on branch-lengths are generally robust to gene tree reconstruction error.

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<![CDATA[Trends in multimorbidity and polypharmacy in the Flemish-Belgian population between 2000 and 2015]]> https://www.researchpad.co/article/5c6c75d6d5eed0c4843d0292

Objectives

The aim of this paper was to describe the time trends in the prevalence of multimorbidity and polypharmacy in Flanders (Belgium) between 2000 and 2015, while controlling for age and sex.

Methods

Data were available from Intego, a Flemish-Belgian general practice-based morbidity registration network. The practice population between 2000 and 2015 was used as the denominator, representing a mean of 159,946 people per year. Age and gender-standardised prevalence rates were used for the trends of multimorbidity and polypharmacy in the total population and for subgroups. Joinpoint regression analyses were used to analyse the time trends and breaks in trends, for the entire population as well as for specific age and sex groups.

Results

Overall, in 2015, 22.7% of the population had multimorbidity, while the overall prevalence of polypharmacy was 20%. Throughout the study period the standardised prevalence rate of multimorbidity rose for both sexes and in all age groups. The largest relative increase in multimorbidity was observed in the younger age groups (up to the age of 50 years). The prevalence of polypharmacy showed a significant increase between 2000 and 2015 for all age groups except the youngest (0–25 years).

Conclusion

For all adult age groups multimorbidity and polypharmacy are frequent, dynamic over time and increasing. This asks for both epidemiological and interventional studies to improve the management of the resulting complex care.

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<![CDATA[Network hubs affect evolvability]]> https://www.researchpad.co/article/5c5b52c6d5eed0c4842bcfcd

The regulatory processes in cells are typically organized into complex genetic networks. However, it is still unclear how this network structure modulates the evolution of cellular regulation. One would expect that mutations in central and highly connected modules of a network (so-called hubs) would often result in a breakdown and therefore be an evolutionary dead end. However, a new study by Koubkova-Yu and colleagues finds that in some circumstances, altering a hub can offer a quick evolutionary advantage. Specifically, changes in a hub can induce significant phenotypic changes that allow organisms to move away from a local fitness peak, whereas the fitness defects caused by the perturbed hub can be mitigated by mutations in its interaction partners. Together, the results demonstrate how network architecture shapes and facilitates evolutionary adaptation.

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<![CDATA[Simultaneous detection of macroevolutionary patterns in phenotypic means and rate of change with and within phylogenetic trees including extinct species]]> https://www.researchpad.co/article/5c644869d5eed0c484c2e64a

Recognizing evolutionary trends in phenotypic means and rates requires the application of phylogenetic comparative methods (PCMs). Most PCMs are unsuited to make full use of fossil information, which is a drawback, given the inclusion of such data improves, and in some cases even corrects, the proper understanding of trait evolution. Here we present a new computer application, written in R, that allows the simultaneous computation of temporal trends in phenotypic mean and evolutionary rate along a phylogeny, and to contrast such patterns among different clades within the tree.

By using simulation experiments, we show the new implementation, names search.trend is as powerful as existing PCM tools in discerning macroevolutionary patterns in phenotypic means and rates, but differently from any other PCM allows comparing individual clades to each other, and provides rich information about trait evolution for all lineages in the tree.

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<![CDATA[Plane inclinations: A critique of hypothesis and model choice in Barbi et al]]> https://www.researchpad.co/article/5c254544d5eed0c48442c3dc

This study highlights how the mortality plateau in Barbi and colleagues can be generated by low-frequency, randomly distributed age-misreporting errors. Furthermore, sensitivity of the late-life mortality plateau in Barbi and colleagues to the particular age range selected for regression is illustrated. Collectively, the simulation of age-misreporting errors in late-life human mortality data and a less-specific model choice than that of Barbi and colleagues highlight a clear alternative hypothesis to explanations based on evolution, the cessation of ageing, and population heterogeneity.

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<![CDATA[Molecular epidemiology and spatiotemporal dynamics of norovirus associated with sporadic acute gastroenteritis during 2013–2017, Zhoushan Islands, China]]> https://www.researchpad.co/article/5b601750463d7e3bf2e777cd

A total of 1 590 fecal swabs and stool samples from sporadic acute gastroenteritis patients of all ages were collected from January 2013 to March 2018 in the Zhoushan Islands, China, with 99 (6.23%) samples subsequently identified as human norovirus (HuNoV) positive. Phylogenetic analysis of partial RdRp and VP1 gene regions identified 10 genotypes of the GII genogroup and 3 genotypes of the GI genogroup. The predominant genotype was GII.P17-GII.17 (42.86%, 33/77), followed by GII.Pe-GII.4_Sydney 2012 (24.68%, 19/77) and GII.P16-GII.2 (12.96%, 10/77). However, the prevailing genotype in the Zhoushan Islands has shifted on three separate occasions. The GII.Pe-GII.4_Sydney_2012 strain was dominant in 2013–2014, the GII.P17-17 strain was dominant in 2015–2016, and the GII.P16-GII.2 strain was dominant in 2017. Divergence analysis showed that the re-emerging GII.P16-GII.2 strains clustered with the Japanese 2010–2012 GII.P16-GII.2 strains, and the time of the most recent common ancestor was estimated to have occurred in 2012 to 2013. The evolutionary rates of the RdRp gene region of the GII.P16 genotype and the VP1 gene region of the GII.2 genotype were 2.64 × 10−3 (95% HPD interval, 2.17–3.08 × 10−3) and 3.36 × 10−3 (95% HPD interval, 2.66–4.04 × 10−3) substitutions/site/year, respectively. The migration pattern of the HuNoV GII.2 genotype in China demonstrated that the re-emerging GII.P16-GII.2 strains were first introduced into Hong Kong from Japan, and then spread from Hong Kong to other coastal areas. Our results also showed that the GII.P16-GII.2 strains in the Zhoushan Islands were likely introduced from Jiangsu Province, China, in 2016.

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<![CDATA[Exceptional Heterogeneity in Viral Evolutionary Dynamics Characterises Chronic Hepatitis C Virus Infection]]> https://www.researchpad.co/article/5989da9dab0ee8fa60ba491b

The treatment of HCV infection has seen significant progress, particularly since the approval of new direct-acting antiviral drugs. However these clinical achievements have been made despite an incomplete understanding of HCV replication and within-host evolution, especially compared with HIV-1. Here, we undertake a comprehensive analysis of HCV within-host evolution during chronic infection by investigating over 4000 viral sequences sampled longitudinally from 15 HCV-infected patients. We compare our HCV results to those from a well-studied HIV-1 cohort, revealing key differences in the evolutionary behaviour of these two chronic-infecting pathogens. Notably, we find an exceptional level of heterogeneity in the molecular evolution of HCV, both within and among infected individuals. Furthermore, these patterns are associated with the long-term maintenance of viral lineages within patients, which fluctuate in relative frequency in peripheral blood. Together, our findings demonstrate that HCV replication behavior is complex and likely comprises multiple viral subpopulations with distinct evolutionary dynamics. The presence of a structured viral population can explain apparent paradoxes in chronic HCV infection, such as rapid fluctuations in viral diversity and the reappearance of viral strains years after their initial detection.

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<![CDATA[Positive Selection Drives Rapid Evolution of the meq Oncogene of Marek’s Disease Virus]]> https://www.researchpad.co/article/5989dac0ab0ee8fa60bb0900

Marek’s disease (MD), caused by Marek’s disease virus (MDV), a poultry-borne alphaherpesvirus, is a devastating disease of poultry causing an estimated annual loss of one billion dollars to poultry producers, worldwide. Despite decades of control through vaccination, MDV field strains continue to emerge having increased virulence. The evolutionary mechanism driving the emergence of this continuum of strains to increased MDV virulence, however, remains largely enigmatic. Increase in MDV virulence has been associated with specific amino acid changes within the C-terminus domain of Mareks’s EcoRI-Q (meq)-encoded oncoprotein. In this study, we sought to determine whether the meq gene has evolved adaptively and whether past vaccination efforts have had any significant effect on the reduction or increase of MDV diversity over time. Our analysis suggests that meq is estimated to be evolving at a much faster rate than most dsDNA viruses, and is comparable with the evolutionary rate of RNA viruses. Interestingly, most of the polymorphisms in meq gene appear to have evolved under positive selection and the time of divergence at the meq locus coincides with the period during which the poultry industry had undergone transitions in management practices including the introduction and widespread use of live attenuated vaccines. Our study has revealed that the decades-long use of vaccines did not reduce MDV diversity, but rather had a stimulating effect on the emergence of field strains with increased genetic diversity until the early 2000s. During the years 2004–2005, there was an abrupt decline in the genetic diversity of field isolates followed by a recovery from this bottleneck in the year 2010. Collectively, these data suggest that vaccination seems to not have had any effect on MDV eradication, but rather had a stimulating effect on MDV emergence through adaptation.

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<![CDATA[Selection on Network Dynamics Drives Differential Rates of Protein Domain Evolution]]> https://www.researchpad.co/article/5989da77ab0ee8fa60b97338

The long-held principle that functionally important proteins evolve slowly has recently been challenged by studies in mice and yeast showing that the severity of a protein knockout only weakly predicts that protein’s rate of evolution. However, the relevance of these studies to evolutionary changes within proteins is unknown, because amino acid substitutions, unlike knockouts, often only slightly perturb protein activity. To quantify the phenotypic effect of small biochemical perturbations, we developed an approach to use computational systems biology models to measure the influence of individual reaction rate constants on network dynamics. We show that this dynamical influence is predictive of protein domain evolutionary rate within networks in vertebrates and yeast, even after controlling for expression level and breadth, network topology, and knockout effect. Thus, our results not only demonstrate the importance of protein domain function in determining evolutionary rate, but also the power of systems biology modeling to uncover unanticipated evolutionary forces.

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<![CDATA[Upon Accounting for the Impact of Isoenzyme Loss, Gene Deletion Costs Anticorrelate with Their Evolutionary Rates]]> https://www.researchpad.co/article/5989db54ab0ee8fa60bdcf92

System-level metabolic network models enable the computation of growth and metabolic phenotypes from an organism’s genome. In particular, flux balance approaches have been used to estimate the contribution of individual metabolic genes to organismal fitness, offering the opportunity to test whether such contributions carry information about the evolutionary pressure on the corresponding genes. Previous failure to identify the expected negative correlation between such computed gene-loss cost and sequence-derived evolutionary rates in Saccharomyces cerevisiae has been ascribed to a real biological gap between a gene’s fitness contribution to an organism “here and now” and the same gene’s historical importance as evidenced by its accumulated mutations over millions of years of evolution. Here we show that this negative correlation does exist, and can be exposed by revisiting a broadly employed assumption of flux balance models. In particular, we introduce a new metric that we call “function-loss cost”, which estimates the cost of a gene loss event as the total potential functional impairment caused by that loss. This new metric displays significant negative correlation with evolutionary rate, across several thousand minimal environments. We demonstrate that the improvement gained using function-loss cost over gene-loss cost is explained by replacing the base assumption that isoenzymes provide unlimited capacity for backup with the assumption that isoenzymes are completely non-redundant. We further show that this change of the assumption regarding isoenzymes increases the recall of epistatic interactions predicted by the flux balance model at the cost of a reduction in the precision of the predictions. In addition to suggesting that the gene-to-reaction mapping in genome-scale flux balance models should be used with caution, our analysis provides new evidence that evolutionary gene importance captures much more than strict essentiality.

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<![CDATA[Human lifespan records are not remarkable but their durations are]]> https://www.researchpad.co/article/5c940587d5eed0c484538b64

Has the maximum human lifespan been reached? The current record stands at 122 years, 164 days and has held for over 20 years and is more than four and three quarter years higher than the previous record. The value and persistence of this record have surprised some researchers, with some even questioning its veracity. There have been previous attempts in the literature to answer questions about how long this record might stand and whether it is truly exceptional but the focus has been mainly on the record ages, using ad hoc tools. This article contributes in two new ways. First we study lifespan records via the (inter-) record times and second we make use of specific tools from statistical Records Theory. We find that the occurrence of the present record was not surprising. We estimate around a 25% chance that the record would have survived until now and around a one in five chance that it will survive until 2050, demonstrating remarkable persistence.

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<![CDATA[Evolutionary and Topological Properties of Genes and Community Structures in Human Gene Regulatory Networks]]> https://www.researchpad.co/article/5989dac7ab0ee8fa60bb2c4b

The diverse, specialized genes present in today’s lifeforms evolved from a common core of ancient, elementary genes. However, these genes did not evolve individually: gene expression is controlled by a complex network of interactions, and alterations in one gene may drive reciprocal changes in its proteins’ binding partners. Like many complex networks, these gene regulatory networks (GRNs) are composed of communities, or clusters of genes with relatively high connectivity. A deep understanding of the relationship between the evolutionary history of single genes and the topological properties of the underlying GRN is integral to evolutionary genetics. Here, we show that the topological properties of an acute myeloid leukemia GRN and a general human GRN are strongly coupled with its genes’ evolutionary properties. Slowly evolving (“cold”), old genes tend to interact with each other, as do rapidly evolving (“hot”), young genes. This naturally causes genes to segregate into community structures with relatively homogeneous evolutionary histories. We argue that gene duplication placed old, cold genes and communities at the center of the networks, and young, hot genes and communities at the periphery. We demonstrate this with single-node centrality measures and two new measures of efficiency, the set efficiency and the interset efficiency. We conclude that these methods for studying the relationships between a GRN’s community structures and its genes’ evolutionary properties provide new perspectives for understanding evolutionary genetics.

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<![CDATA[Functional Sites Induce Long-Range Evolutionary Constraints in Enzymes]]> https://www.researchpad.co/article/5989daacab0ee8fa60ba99df

Functional residues in proteins tend to be highly conserved over evolutionary time. However, to what extent functional sites impose evolutionary constraints on nearby or even more distant residues is not known. Here, we report pervasive conservation gradients toward catalytic residues in a dataset of 524 distinct enzymes: evolutionary conservation decreases approximately linearly with increasing distance to the nearest catalytic residue in the protein structure. This trend encompasses, on average, 80% of the residues in any enzyme, and it is independent of known structural constraints on protein evolution such as residue packing or solvent accessibility. Further, the trend exists in both monomeric and multimeric enzymes and irrespective of enzyme size and/or location of the active site in the enzyme structure. By contrast, sites in protein–protein interfaces, unlike catalytic residues, are only weakly conserved and induce only minor rate gradients. In aggregate, these observations show that functional sites, and in particular catalytic residues, induce long-range evolutionary constraints in enzymes.

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<![CDATA[Mosasauroid phylogeny under multiple phylogenetic methods provides new insights on the evolution of aquatic adaptations in the group]]> https://www.researchpad.co/article/5989db5aab0ee8fa60bdf497

Mosasauroids were a successful lineage of squamate reptiles (lizards and snakes) that radiated during the Late Cretaceous (95–66 million years ago). They can be considered one of the few lineages in the evolutionary history of tetrapods to have acquired a fully aquatic lifestyle, similarly to whales, ichthyosaurs and plesiosaurs. Despite a long history of research on this group, their phylogenetic relationships have only been tested so far using traditional (unweighted) maximum parsimony. However, hypotheses of mosasauroid relationships and the recently proposed multiple origins of aquatically adapted pelvic and pedal features in this group can be more thoroughly tested by methods that take into account variation in branch lengths and evolutionary rates. In this study, we present the first mosasauroid phylogenetic analysis performed under different analytical methods, including maximum likelihood, Bayesian inference, and implied weighting maximum parsimony. The results indicate a lack of congruence in the topological position of halisaurines and Dallasaurus. Additionally, the genus Prognathodon is paraphyletic under all hypotheses. Interestingly, a number of traditional mosasauroid clades become weakly supported, or unresolved, under Bayesian analyses. The reduced resolutions in some consensus trees create ambiguities concerning the evolution of fully aquatic pelvic/pedal conditions under many analyses. However, when enough resolution was obtained, reversals of the pelvic/pedal conditions were favoured by parsimony and likelihood ancestral state reconstructions instead of independent origins of aquatic features in mosasauroids. It is concluded that most of the observed discrepancies among the results can be associated with different analytical procedures, but also due to limited postcranial data on halisaurines, yaguarasaurines and Dallasaurus.

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<![CDATA[Effects of Darwinian Selection and Mutability on Rate of Broadly Neutralizing Antibody Evolution during HIV-1 Infection]]> https://www.researchpad.co/article/5989db05ab0ee8fa60bc7f06

Accumulation of somatic mutations in antibody variable regions is critical for antibody affinity maturation, with HIV-1 broadly neutralizing antibodies (bnAbs) generally requiring years to develop. We recently found that the rate at which mutations accumulate decreases over time, but the mechanism governing this slowing is unclear. In this study, we investigated whether natural selection and/or mutability of the antibody variable region contributed significantly to observed decrease in rate. We used longitudinally sampled sequences of immunoglobulin transcripts of single lineages from each of 3 donors, as determined by next generation sequencing. We estimated the evolutionary rates of the complementarity determining regions (CDRs), which are most significant for functional selection, and found they evolved about 1.5- to 2- fold faster than the framework regions. We also analyzed the presence of AID hotspots and coldspots at different points in lineage development and observed an average decrease in mutability of less than 10 percent over time. Altogether, the correlation between Darwinian selection strength and evolutionary rate trended toward significance, especially for CDRs, but cannot fully explain the observed changes in evolutionary rate. The mutability modulated by AID hotspots and coldspots changes correlated only weakly with evolutionary rates. The combined effects of Darwinian selection and mutability contribute substantially to, but do not fully explain, evolutionary rate change for HIV-1-targeting bnAb lineages.

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<![CDATA[Large-Scale Phylogenomic Analysis Reveals the Complex Evolutionary History of Rabies Virus in Multiple Carnivore Hosts]]> https://www.researchpad.co/article/5989db4dab0ee8fa60bdaeb3

The natural evolution of rabies virus (RABV) provides a potent example of multiple host shifts and an important opportunity to determine the mechanisms that underpin viral emergence. Using 321 genome sequences spanning an unprecedented diversity of RABV, we compared evolutionary rates and selection pressures in viruses sampled from multiple primary host shifts that occurred on various continents. Two major phylogenetic groups, bat-related RABV and dog-related RABV, experiencing markedly different evolutionary dynamics were identified. While no correlation between time and genetic divergence was found in bat-related RABV, the evolution of dog-related RABV followed a generally clock-like structure, although with a relatively low evolutionary rate. Subsequent molecular clock dating indicated that dog-related RABV likely underwent a rapid global spread following the intensification of intercontinental trade starting in the 15th century. Strikingly, although dog RABV has jumped to various wildlife species from the order Carnivora, we found no clear evidence that these host-jumping events involved adaptive evolution, with RABV instead characterized by strong purifying selection, suggesting that ecological processes also play an important role in shaping patterns of emergence. However, specific amino acid changes were associated with the parallel emergence of RABV in ferret-badgers in Asia, and some host shifts were associated with increases in evolutionary rate, particularly in the ferret-badger and mongoose, implying that changes in host species can have important impacts on evolutionary dynamics.

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