Neutral Model Of Evolution Research Articles

The principle of ecological and molecular consensus in reconstructed plague microbe <i>Yersinia pestis</i> phylogeny

In the second half of the 20th century, through the efforts of scientists from many countries, a coherent theory of natural plague foci (sylvatic plague) was formulated, attempted to describe the history of the origin and evolution of the causative agent of plague infection, the microbeYersinia pestis. But the accumulated knowledge in this regard remained extremely limited. Envisioned by the modern phylogenetics, the methods of phylogenetic constructions in the pregenomic time were rather primitive, “manual”, characteristic of early empirico-intuitive Haeckel phylogenetics. Since the beginning of the 21st century, the introduction of genomic methodologies in the study of the plague pathogen allowed to detail the intraspecific diversity (subspecies, genovariants) of this particularly dangerous pathogen at the level of geographical and local populations (individual natural foci) around the world and to bring the diagnostics and description of intraspecific diversity to a high degree of perfection. Two important discoveries were made. First, the direct ancestor of the plague microbe was reliably established, it turned out to be the causative agent of intestinal infection — Far Eastern scarlet-like fever (Y. pseudotuberculosis0:1b). Secondly, the evolutionary youth of the plague pathogen was shown, the “molecular clock” showed the time of its divergence from the ancestral population no earlier than 30 thousand years ago. Thus, the root of the phylogenetic tree ofY. pestiswas fully characterized. Nevertheless, molecular genetic (MG) achievements do not yet allow to reveal the secrets of its phylogeny, i.e. the origin and sequence of world expansion. The most important reason is the high dependence of the MG of phylogeny reconstructions on the choice of evolutionary model for the analyzed characters: the model of neutral evolution is traditionally accepted, but its adequacy in relation toY. pestisphylogeny is questioned by many well-known ecological (in the broad sense) facts. At the same time, MG achievements contributed to the creation of an ecological (ECO) approach based on the provisions of the theory of natural plague foci in an updated version, according to which the plague pathogen is an evolutionarily young pathogen descended from a psychrophilic pseudotuberculous ancestor. The presumptive ECO scenario has no obvious natural-scientific and historical contradictions and can serve as a null hypothesis for improving the MG methodology of phylogenetic constructions for plague and other similar microbes. It is suggested that the creation of a real phylogeny of the plague microbe is possible only based on integration of MG and ECO approaches.

Detecting diversifying selection for a trait from within and between-species genotypes and phenotypes.

To quantify selection acting on a trait, methods have been developed using either within or between-species variation. However, methods using within-species variation do not integrate the changes at the macroevolutionary scale. Conversely, current methods using between-species variation usually discard within-species variation, thus not accounting for processes at the micro-evolutionary scale. The main goal of this study is to define a neutrality index for a quantitative trait, by combining withinand between-species variation. This neutrality index integrates nucleotide polymorphism and divergence for normalizing trait variation. As such, it does not require estimation of population size nor of time of speciation for normalization. Our index can be used to seek deviation from the null model of neutral evolution, and test for diversifying selection. Applied to brain mass and body mass at the mammalian scale, we show that brain mass is under diversifying selection. Finally, we show that our test is not sensitive to the assumption that population sizes, mutation rates and generation time are constant across the phylogeny, and automatically adjust for it.

Selection leads to false inferences of introgression using popular methods.

Detecting introgression between closely related populations or species is a fundamental objective in evolutionary biology. Existing methods for detecting migration and inferring migration rates from population genetic data often assume a neutral model of evolution. Growing evidence of the pervasive impact of selection on large portions of the genome across diverse taxa suggests that this assumption is unrealistic in most empirical systems. Further, ignoring selection has previously been shown to negatively impact demographic inferences (e.g. of population size histories). However, the impacts of biologically realistic selection on inferences of migration remain poorly explored. Here, we simulate data under models of background selection, selective sweeps, balancing selection, and adaptive introgression. We show that ignoring selection sometimes leads to false inferences of migration in popularly used methods that rely on the site frequency spectrum. Specifically, balancing selection and some models of background selection result in the rejection of isolation-only models in favor of isolation-with-migration models and lead to elevated estimates of migration rates. BPP, a method that analyzes sequence data directly, showed false positives for all conditions at recent divergence times, but balancing selection also led to false positives at medium-divergence times. Our results suggest that such methods may be unreliable in some empirical systems, such that new methods that are robust to selection need to be developed.

Evolution of chromosomal inversions across an avian radiation.

Chromosomal inversions are structural mutations that can play a prominent role in adaptation and speciation. Inversions segregating across species boundaries (trans-species inversions) are often taken as evidence for ancient balancing selection or adaptive introgression but can also be due to incomplete lineage sorting (ILS). Using whole-genome resequencing data from 18 populations of 11 recognized munia species in the genus Lonchura (N = 176 individuals), we identify four large para- and pericentric inversions ranging in size from 4 to 20 Mb. All four inversions co-segregate across multiple species and predate the numerous speciation events associated with the rapid radiation of this clade across the prehistoric Sahul (Australia, New Guinea) and Bismarck Archipelago. Using coalescent theory, we infer that trans-specificity is improbable for neutrally segregating variation despite substantial ILS characterizing this young radiation. Instead, maintenance of all three autosomal inversions (chr1, chr5, chr6) is best explained by selection acting along eco-geographic clines not observed for the collinear parts of the genome. In addition, the large sex chromosome inversion largely aligns with species boundaries and shows signatures of repeated positive selection for both alleles. This study provides evidence for trans-species inversion polymorphisms involved in both adaptation and speciation. It further highlights the importance of informing selection inference using a null model of neutral evolution derived from the collinear part of the genome.

Evidence for Selection on Mitochondrial OXPHOS Genes in the Mediterranean Killifish Aphanius fasciatus Valenciennes, 1821.

Mitochondrial oxidative phosphorylation (OXPHOS) genes are a system subject to selection under determined environmental constraints despite a neutral evolution model that has long been hypothesized for the mitochondrial genome. In this study, the sequences of ND1, Cytb, and COI OXPHOS genes were analyzed in six populations of the eurythermal and euryhaline killifish A. fasciatus, to detect non-synonymous mutations leading to amino acid changes and to check whether selection acted on them using tests of recombination and selection. The results indicate a high COI and Cytb gene diversity and a high percentage of private haplotypes in all populations. In the Greek population, non-synonymous nucleotide substitutions were observed in the N-terminal region of COI and Cytb. Positively selected sites were also found. The information we obtained from the mitochondrial DNA sequences of A. fasciatus adds to the growing data on selective pressure acting on mitochondrial DNA in non-model species. These results should be explored from the perspective of the local adaptation of eurythermal and euryhaline species and supported using experimental evidence to better understand the interplay between historical climatic events and local adaptation and how each of them contributes to shaping the genetic structure of this species.

A Comparative Analysis of Selection Pressures Suffered by Mitochondrial Genomes in Two Planthopper Species with Divergent Climate Distributions

Mitochondrial DNA (mtDNA) has been widely used as a valuable tool in studies related to evolution and population genetics, under the implicit assumption of neutral evolution. However, recent studies suggest that natural selection also plays a significant role in shaping mitochondrial genome evolution, although the specific driving forces remain elusive. In this study, we aimed to investigate whether and how climate influences mitochondrial genome evolution by comparing the selection pressures acting on mitochondrial genomes between two rice planthoppers, Sogatella furcifera (Horváth) and Laodelphax striatellus (Fallén), which have different climate distributions. We employed the dN/dS method, MK test and Tajima’s D tests for our analysis. Our results showed that the mitochondrial genomes of the two species appear to undergo predominantly purifying selection, consistent with the nearly neutral evolution model. However, we observed varied degrees of purifying selection among the 13 protein-coding genes. Notably, ND1, ND2, ND6, COIII, and ATP8 exhibited significantly stronger purifying selection and greater divergence between the two species compared to the other genes. Additionally, we observed relatively stronger purifying selection in the mitochondrial genomes of S. furcifera compared to L. striatellus. This difference could be attributed to varying metabolic requirements arising from distinct habitats or other factors that are unclear here. Furthermore, we speculate that mito-nuclear epistatic interactions may play a role in maintaining nonsynonymous polymorphisms, particularly for COI and COII. Overall, our results shed some light on the influence of climate on mitochondrial genome evolution.

A General Framework for Neutrality Tests Based on the Site Frequency Spectrum.

One of the main necessities for population geneticists is the availability of sensitive statistical tools that enable to accept or reject the standard Wright-Fisher model of neutral evolution. A number of statistical tests have been developed to detect specific deviations from the null frequency spectrum in different directions (e.g., Tajima's D, Fu and Li's F and D tests, Fay and Wu's H). A general framework exists to generate all neutrality tests that are linear functions of the frequency spectrum. In this framework, it is possible to develop a family of optimal tests with almost maximum power against a specific alternative evolutionary scenario. In this paper we provide a thorough discussion of the structure and properties of linear and nonlinear neutrality tests. First, we present the general framework for linear tests and emphasise the importance of the property of scalability with the sample size (that is, the interpretation of the tests should not depend on the sample size), which, if missing, can lead to errors in interpreting the data. After summarising the motivation and structure of linear optimal tests, we present a more general framework for the optimisation of linear tests, leading to a new family of tunable neutrality tests. In a further generalisation, we extend the framework to nonlinear neutrality tests and we derive nonlinear optimal tests for polynomials of any degree in the frequency spectrum.

Inferring human neutral genetic variation from craniodental phenotypes.

There is a growing consensus that global patterns of modern human cranial and dental variation are shaped largely by neutral evolutionary processes, suggesting that craniodental features can be used as reliable proxies for inferring population structure and history in bioarchaeological, forensic, and paleoanthropological contexts. However, there is disagreement on whether certain types of data preserve a neutral signature to a greater degree than others. Here, we address this unresolved question and systematically test the relative neutrality of four standard metric and nonmetric craniodental data types employing an extensive computational genotype-phenotype comparison across modern populations from around the world. Our computation draws on the largest existing data sets currently available, while accounting for geographically structured environmental variation, population sampling uncertainty, disparate numbers of phenotypic variables, and stochastic variation inherent to a neutral model of evolution. Our results reveal that the four data types differentially capture neutral genomic variation, with highest signals preserved in dental nonmetric and cranial metric data, followed by cranial nonmetric and dental metric data. Importantly, we demonstrate that combining all four data types together maximizes the neutral genetic signal compared with using them separately, even with a limited number of phenotypic variables. We hypothesize that this reflects a lower level of genetic integration through pleiotropy between, compared to within, the four data types, effectively forming four different modules associated with relatively independent sets of loci. Therefore, we recommend that future craniodental investigations adopt holistic combined data approaches, allowing for more robust inferences about underlying neutral genetic variation.

Parallelism in Speciation and Intraspecific Diversification of the Plague Microbe <i>Yersinia pestis</i>

Modern “molecular genetic (MG) phylogenies” of the plague microbe Yersinia pestis, built on models of neutral evolution using statistical methods of phylogenetic analysis, contradict numerous obvious environmental (ECO) patterns and are not consistent with the concept of adaptatiogenesis. The reason for the discrepancy between MG and ECO phylogenies is seen in the underestimation by the MG approach of parallelisms in the processes of speciation and intraspecific diversification of the plague microbe. ECO methods showed the parallel tritope (almost) simultaneous speciation of three primary genovariants (populations, subspecies) Y. pestis 2.ANT3, 3.ANT2 and 4.ANT1 in three geographical populations of the Mongolian marmot (Marmota sibirica), which in the MG approach is mistaken for polytomy (“Big Bang”), caused by unknown natural phenomena on the eve of the first pandemic (Justinian’s plague, 6th-8th centuries AD). The discrepancy between MG and ECO interpretations of the evolution of intraspecifically-derived phylogenetic sub-branches 0.PE and 2.MED is also associated with parallel evolutionary processes in independent lines, based on genovariants 2.ANT3, 3.ANT2 and 4.ANT1. Independence of these phylogenetic lines and associated with them parallelisms of sub-branches 0.PE and 2.MED are not taken into account in the MG approach. The prospect of creating a real phylogenetic tree for Y. pestis depends on a creative synthesis of the two approaches – MG and ECO.

Genetic diversity of the cultivated Salvia miltiorrhiza populations revealed by four intergenic spacers.

For better understanding the genetic diversity and phylogeny of the cultivated Salvia miltiorrhiza populations, four intergenic spacer sequences, ETS, psbA-trnH, trnL-trnF, and ycf1-rps15 of the 40 populations collected from China were Polymerase Chain Reaction (PCR) amplified, analyzed both individually and in combination. Haplotype diversity analysis showed that the cultivated S. miltiorrhiza populations had a very rich genetic diversity and an excellent capacity to resist environmental pressure. The best-fit nucleotide substitution models for ETS, psbA-trnH, trnL-trnF, ycf1-rps15, and their combined sequences were HKY+I, T92, T92, T92+G, and T92+G, respectively; the nucleotide conversion frequency in the combined sequences was lower than the transversion, and the relatively high nucleotide substitution frequencies suggests its high genetic variability. Neutral tests showed that the spacer sequences of the populations conform with the neutral evolution model, and there has been no current expansion events occurred. Phylogeny analyses based on both the individual and the combined sequences showed that the 40 populations were clustered in two clades with a very similar topological structure. The discrimination rate of the combined sequence marker is significantly increased to 52.5% (21 populations) over the highest 35% (13 populations) by the single marker of ETS, though still inadequate but a big step forward. Further exploration of more DNA markers is needed. This study for the first time revealed the rich genetic diversity and phylogeny of the currently cultivated S. miltiorrhiza populations in China and provides novel alternative molecular markers for the genetic identification and resources evaluation of the cultivated S. miltiorrhiza populations.

Genomic patterns of structural variation among diverse genotypes of Sorghum bicolor and a potential role for deletions in local adaptation.

Genomic structural mutations, especially deletions, are an important source of variation in many species and can play key roles in phenotypic diversification and evolution. Previous work in many plant species has identified multiple instances of structural variations (SVs) occurring in or near genes related to stress response and disease resistance, suggesting a possible role for SVs in local adaptation. Sorghum [Sorghum bicolor (L.) Moench] is one of the most widely grown cereal crops in the world. It has been adapted to an array of different climates as well as bred for multiple purposes, resulting in a striking phenotypic diversity. In this study, we identified genome-wide SVs in the Biomass Association Panel, a collection of 347 diverse sorghum genotypes collected from multiple countries and continents. Using Illumina-based, short-read whole-genome resequencing data from every genotype, we found a total of 24,648 SVs, including 22,359 deletions. The global site frequency spectrum of deletions and other types of SVs fit a model of neutral evolution, suggesting that the majority of these mutations were not under any types of selection. Clustering results based on single nucleotide polymorphisms separated the genotypes into eight clusters which largely corresponded with geographic origins, with many of the large deletions we uncovered being unique to a single cluster. Even though most deletions appeared to be neutral, a handful of cluster-specific deletions were found in genes related to biotic and abiotic stress responses, supporting the possibility that at least some of these deletions contribute to local adaptation in sorghum.

Clinical and genomic characterization of neutral tumor evolution in Head and Neck Squamous Cell Carcinoma

Recent studies suggest that a significant proportion of cancers undergo neutral tumor evolution. We applied neutral evolution model in HNSCC patients from The Cancer Genome Atlas (TCGA). To ensure the accuracy of classification results, a sample with the purity of tumor <0.7 was excluded. A tumor sample was considered to evolve neutrally if R2 ≥ 0.98. We found that about 16% of HNSCC patients undergo neutral tumor evolution. We showed that neutral evolution HNSCC patients have better prognosis and higher activities of immune response pathways, and the numbers of co-occurring mutation events and significantly positive selection mutations are significantly less than non-neutral evolution HNSCC patients. In conclusion, we described a comprehensive clinical and genomic characteristics of neutral tumor evolution in Head and Neck Squamous Cell Carcinoma (HNSCC), and provided evidence that the evolution history of HNSCC has both clinical and biological implications.

Neutral syndrome.

Neutral models of evolution assume the absence of natural selection. Formerly confined to ecology and evolutionary biology, neutral models are spreading. In recent years they've been applied to explaining the diversity of baby names, scientific citations, cryptocurrencies, pot decorations, literary lexica, tumour variants and much more besides. Here, we survey important neutral models and highlight their similarities. We investigate the most widely used tests of neutrality, show that they are weak and suggest more powerful methods. We conclude by discussing the role of neutral models in the explanation of diversity. We suggest that the ability of neutral models to fit low-information distributions should not be taken as evidence for the absence of selection. Nevertheless, many studies, in increasingly diverse fields, make just such claims. We call this tendency 'neutral syndrome'.

Invasion Rate Versus Diversity in Population Dynamics with Catastrophes

A key question in the current diversity crisis is how diversity has been maintained throughout evolution and how to preserve it. Modern coexistence theories suggest that a high invasion rate of rare new types is directly related to diversity. We show that adding almost any mechanism of catastrophes to a stochastic birth, death, and mutation process with limited carrying capacity induces a novel phase transition characterized by a positive invasion rate but a low diversity. In this phase, new types emerge and grow rapidly, but the resulting growth of very large types decreases diversity. This model also resolves two major drawbacks of neutral evolution models: their failure to explain balancing selection without resorting to fitness differences and the unrealistic time required for the creation of the observed large types. We test this model on a classical case of genetic polymorphism: the HLA locus.

Neutral and niche forces as drivers of species selection

The evolutionary and ecological processes behind the origin of species are among the most fundamental problems in biology. In fact, many theoretical hypothesis on different type of speciation have been proposed. In particular, models of sympatric speciation leading to the formation of new species without geographical isolation, are based on the niche hypothesis: the diversification of the population is induced by the competition for a limited set of available resources. Interestingly, neutral models of evolution have shown that stochastic forces are sufficient to generate coexistence of different species. In this work, we put forward this dichotomy within the context of species formation, studying how neutral and niche forces contribute to sympatric speciation in a model ecosystem. In particular, we study the evolution of a population of individuals with asexual reproduction whose inherited characters or phenotypes are specified by both niche-based and neutral traits. We analyze the stationary state of the dynamics, and study the distribution of individuals in the whole phenotypic space. We show, both numerically and analytically, that there is a non-trivial coupling between neutral and niche forces induced by stochastic effects in the evolution of the population allowing the formation of clusters, that is, species in the phenotypic space. Remarkably, our framework can be generalized also to sexual reproduction or other type of population dynamics.

A neutral evolution test derived from a theoretical amino acid substitution model

A neutral evolution model that explicitly considers codons, amino acids, and the degeneracy of the genetic code is developed. The model is built from nucleotides up to amino acids, and it represents a refinement of the neutral theory of molecular evolution. The model is based on a stochastic process that leads to a stationary probability distribution of amino acids. The latter is used as a neutral test of evolution. We provide some examples for assessing the neutrality test for a small set of protein sequences. The Jukes-Cantor model is generalized to deal with amino acids and it is compared with our neutral model, along with the empirical BLOSUM62 substitution model. The neutral test provides a baseline to which the evolution of any protein can be analyzed, and it clearly helps in discerning putative amino acids with unexpected frequencies that might be under positive or negative selection. Our model and neutral test are as universal as the standard genetic code.

Clonal dynamics in osteosarcoma defined by RGB marking

Osteosarcoma is a type of bone tumour characterized by considerable levels of phenotypic heterogeneity, aneuploidy, and a high mutational rate. The life expectancy of osteosarcoma patients has not changed during the last three decades and thus much remains to be learned about the disease biology. Here, we employ a RGB-based single-cell tracking system to study the clonal dynamics occurring in a de novo-induced murine osteosarcoma model. We show that osteosarcoma cells present initial polyclonal dynamics, followed by clonal dominance associated with adaptation to the microenvironment. Interestingly, the dominant clones are composed of subclones with a similar tumour generation potential when they are re-implanted in mice. Moreover, individual spontaneous metastases are clonal or oligoclonal, but they have a different cellular origin than the dominant clones present in primary tumours. In summary, we present evidence that osteosarcomagenesis can follow a neutral evolution model, in which different cancer clones coexist and propagate simultaneously.

Genetic structure and diversity of Harmonia axyridis populations in Shaanxi Province, China.

Harmonia axyridis, one of the most important insect predators, has been widely used in biological control in agriculture. In this study, the mitochondrial COII gene was used as genetic marker to investigate the genetic structure and diversity of H. axyridis geographic populations distributed in Shaanxi Province. Level of genetic differentiation and gene flow among different populations of H. axyridis were analyzed. For all the 529 H. axyridis individuals from 21 populations, 15 haplotypes were observed (named as Hap1-Hap15). Hap1 and Hap2 were dominant haplotypes in all sampled individuals, accounting for 34.4% and 37.6% respectively. The overall haplotype diver-sity was 0.732, and it ranged from 0.652 to 0.786 within population. The average gene flow (Nm) among 21 populations was 10.13, and the overall FST value was 0.024, implying low genetic diffe-rentiation among all populations. Results from neutrality tests suggested that H. axyridis populations followed the neutral evolution model and the population size remained stable. Molecular variance analysis (AMOVA) showed high proportion of total genetic variance attributed to variations within populations. Phylogenetic tree based on Nei's genetic distance of different geographic populations showed clear divergence between northern, central, and southern Shaanxi groups. Results from Mantel test suggested that the genetic distance was weakly correlated with geographical distance between populations. Geographical pattern of genetic structure and diversity in populations from different regions indicated weak gene flow between northern, central, and southern Shaanxi due to Qinling Mountains barrier and climate difference.

Stochastic processes constrain the within and between host evolution of influenza virus.

The evolutionary dynamics of influenza virus ultimately derive from processes that take place within and between infected individuals. Here we define influenza virus dynamics in human hosts through sequencing of 249 specimens from 200 individuals collected over 6290 person-seasons of observation. Because these viruses were collected from individuals in a prospective community-based cohort, they are broadly representative of natural infections with seasonal viruses. Consistent with a neutral model of evolution, sequence data from 49 serially sampled individuals illustrated the dynamic turnover of synonymous and nonsynonymous single nucleotide variants and provided little evidence for positive selection of antigenic variants. We also identified 43 genetically-validated transmission pairs in this cohort. Maximum likelihood optimization of multiple transmission models estimated an effective transmission bottleneck of 1-2 genomes. Our data suggest that positive selection is inefficient at the level of the individual host and that stochastic processes dominate the host-level evolution of influenza viruses.

Examination of Signatures of Recent Positive Selection on Genes Involved in Human Sialic Acid Biology.

Sialic acids are nine carbon sugars ubiquitously found on the surfaces of vertebrate cells and are involved in various immune response-related processes. In humans, at least 58 genes spanning diverse functions, from biosynthesis and activation to recycling and degradation, are involved in sialic acid biology. Because of their role in immunity, sialic acid biology genes have been hypothesized to exhibit elevated rates of evolutionary change. Consistent with this hypothesis, several genes involved in sialic acid biology have experienced higher rates of non-synonymous substitutions in the human lineage than their counterparts in other great apes, perhaps in response to ancient pathogens that infected hominins millions of years ago (paleopathogens). To test whether sialic acid biology genes have also experienced more recent positive selection during the evolution of the modern human lineage, reflecting adaptation to contemporary cosmopolitan or geographically-restricted pathogens, we examined whether their protein-coding regions showed evidence of recent hard and soft selective sweeps. This examination involved the calculation of four measures that quantify changes in allele frequency spectra, extent of population differentiation, and haplotype homozygosity caused by recent hard and soft selective sweeps for 55 sialic acid biology genes using publicly available whole genome sequencing data from 1,668 humans from three ethnic groups. To disentangle evidence for selection from confounding demographic effects, we compared the observed patterns in sialic acid biology genes to simulated sequences of the same length under a model of neutral evolution that takes into account human demographic history. We found that the patterns of genetic variation of most sialic acid biology genes did not significantly deviate from neutral expectations and were not significantly different among genes belonging to different functional categories. Those few sialic acid biology genes that significantly deviated from neutrality either experienced soft sweeps or population-specific hard sweeps. Interestingly, while most hard sweeps occurred on genes involved in sialic acid recognition, most soft sweeps involved genes associated with recycling, degradation and activation, transport, and transfer functions. We propose that the lack of signatures of recent positive selection for the majority of the sialic acid biology genes is consistent with the view that these genes regulate immune responses against ancient rather than contemporary cosmopolitan or geographically restricted pathogens.