The extent of somatic mutation and clonal selection in the human bladder remains unknown. We sequenced 2097 bladder microbiopsies from 20 individuals using targeted (
= 1914 microbiopsies), ...whole-exome (
= 655), and whole-genome (
= 88) sequencing. We found widespread positive selection in 17 genes. Chromatin remodeling genes were frequently mutated, whereas mutations were absent in several major bladder cancer genes. There was extensive interindividual variation in selection, with different driver genes dominating the clonal landscape across individuals. Mutational signatures were heterogeneous across clones and individuals, which suggests differential exposure to mutagens in the urine. Evidence of APOBEC mutagenesis was found in 22% of the microbiopsies. Sequencing multiple microbiopsies from five patients with bladder cancer enabled comparisons with cancer-free individuals and across histological features. This study reveals a rich landscape of mutational processes and selection in normal urothelium with large heterogeneity across clones and individuals.
Anisogamy predisposes the sexes to very different patterns of selection on shared traits. Selective differences between the sexes may manifest as changes in the direction or strength of selection ...acting on shared phenotypes. Although previous studies have found evidence for widespread differences in the direction of selection between the sexes, surprisingly little is known regarding potential differences in the magnitude of selection and whether such differences might be confined to specific components of fitness. We conducted a meta-analysis using 865 estimates of phenotypic selection from wild populations to characterize sex differences in the strength of selection and to ask whether different components of fitness exhibit differences in sex bias in the strength of selection. Overall, consistent with past results, we find evidence of male bias in the strength of selection, driven primarily by components of fitness related to mating success and we discuss several evolutionary implications.
Genomic selection (GS) facilitates the rapid selection of superior genotypes and accelerates the breeding cycle. In this review, we discuss the history, principles, and basis of GS and ...genomic-enabled prediction (GP) as well as the genetics and statistical complexities of GP models, including genomic genotype×environment (G×E) interactions. We also examine the accuracy of GP models and methods for two cereal crops and two legume crops based on random cross-validation. GS applied to maize breeding has shown tangible genetic gains. Based on GP results, we speculate how GS in germplasm enhancement (i.e., prebreeding) programs could accelerate the flow of genes from gene bank accessions to elite lines. Recent advances in hyperspectral image technology could be combined with GS and pedigree-assisted breeding.
In recent years, the global climate has changed, resulting in drastic fluctuations in rainfall patterns and increasing temperature. Sudden climate changes can cause significant economic losses to countries worldwide.
Genetic improvement of several economically important crops during the 20th century using phenotypic, pedigree, and performance data was very successful. However, signs of grain yield stagnation in some crops, especially in drought-stressed and semi-arid regions, are evident.
Genomic selection offers the opportunity to increase grain production in less time. International Maize and Wheat Improvement Center (CIMMYT) maize breeding research in Sub-Saharan Africa, India, and Mexico has shown that genomic selection can reduce the breeding interval cycle to at least half the conventional time and produces lines that, in hybrid combinations, significantly increase grain yield performance over that of commercial checks.
Public and private investment in crop genomic selection research should increase to successfully develop in less time germplasm that is adapted to sudden climate change.
•Two new feature selection methods are proposed based on joint mutual information.•The methods use joint mutual information with maximum of the minimum criterion.•The methods address the problem of ...selection of redundant and irrelevant features.•The methods are evaluated using eleven public data sets and five competing methods.•The proposed JMIM method outperforms five competing methods in terms of accuracy.
Feature selection is used in many application areas relevant to expert and intelligent systems, such as data mining and machine learning, image processing, anomaly detection, bioinformatics and natural language processing. Feature selection based on information theory is a popular approach due its computational efficiency, scalability in terms of the dataset dimensionality, and independence from the classifier. Common drawbacks of this approach are the lack of information about the interaction between the features and the classifier, and the selection of redundant and irrelevant features. The latter is due to the limitations of the employed goal functions leading to overestimation of the feature significance.
To address this problem, this article introduces two new nonlinear feature selection methods, namely Joint Mutual Information Maximisation (JMIM) and Normalised Joint Mutual Information Maximisation (NJMIM); both these methods use mutual information and the ‘maximum of the minimum’ criterion, which alleviates the problem of overestimation of the feature significance as demonstrated both theoretically and experimentally. The proposed methods are compared using eleven publically available datasets with five competing methods. The results demonstrate that the JMIM method outperforms the other methods on most tested public datasets, reducing the relative average classification error by almost 6% in comparison to the next best performing method. The statistical significance of the results is confirmed by the ANOVA test. Moreover, this method produces the best trade-off between accuracy and stability.
With the availability of high-density marker maps and cost-effective genotyping, genomic selection methods may provide faster genetic gain than can be achieved by current selection methods based on ...phenotypes and the pedigree. Here we investigate some of the factors driving the accuracy of genomic selection, namely marker density and marker type (i.e., microsatellite and SNP markers), and the use of marker haplotypes versus marker genotypes alone. Different densities were tested with marker densities equivalent to 2, 1, 0.5, and 0.25Ne markers/morgan using microsatellites and 8, 4, 2, and 1Ne markers/morgan using SNP, where 1Ne markers/morgan means 100 markers per morgan, if effective size (Ne) is 100. Marker characteristics and linkage disequilibria were obtained by simulating a population over 1,000 generations to achieve a mutation drift balance. The marker designs were evaluated for their accuracy of predicting breeding values from either estimating marker effects or estimating effects of haplotypes based upon combining 2 markers. Using microsatellites as direct marker effects, the accuracy of selection increased from 0.63 to 0.83 as the density increased from 0.25Ne/morgan to 2Ne/morgan. Using SNP markers as direct marker effects, the accuracy of selection increased from 0.69 to 0.86 as the density increased from 1Ne/morgan to 8Ne/morgan. The SNP markers required a 2 to 3 times greater density compared with using microsatellites to achieve a similar accuracy. The biases that genomic selection EBV often show are due to the prediction of marker effects instead of QTL effects, and hence, genomic selection EBV may need rescaling for practical use. Using haplotypes resulted in similar or reduced accuracies compared with using direct marker effects. In practical situations, this means that it is advantageous to use direct marker effects, because this avoids the estimation of marker phases with the associated errors. In general, the results showed that the accuracy remained responsive with small bias to increasing marker density at least up to 8Ne SNP/morgan, where the effective population size was 100 and with the genomic model assumed. For a 30-morgan genome and Ne = 100, this implies that about approximately 24,000 SNP are needed.
Males and females share most of their genomes and express many of the same traits, yet the sexes often have markedly different selective optima for these shared traits. This sexually antagonistic ...(SA) selection generates intralocus sexual conflict that is thought to be resolved through the evolution of sexual dimorphism. However, we currently know little about the prevalence of SA selection, the components of fitness that generate sexual antagonism, or the relationship between sexual dimorphism and current SA selection. We reviewed published studies to address these questions, using 424 selection estimates representing 89 traits from 34 species. Males and females often differed substantially in the direction and magnitude of selection on shared traits, although statistically significant SA selection was relatively uncommon. Sexual selection generated stronger sexual antagonism than fecundity or viability selection, and these individual components of fitness tended to reinforce one another to generate even stronger sexual antagonism for net fitness. Traits exhibiting strong sexual dimorphism exhibited greater SA selection than did weakly dimorphic traits, although this pattern was not significant after we controlled for the inclusion of multiple traits nested within species. Our results suggest that intralocus sexual conflict often may persist despite the evolution of sexual dimorphism.
Over the past two decades, comparative sequence analysis using codon-substitution models has been honed into a powerful and popular approach for detecting signatures of natural selection from ...molecular data. A substantial body of work has focused on developing a class of "branch-site" models which permit selective pressures on sequences, quantified by the ω ratio, to vary among both codon sites and individual branches in the phylogeny. We develop and present a method in this class, adaptive branch-site random effects likelihood (aBSREL), whose key innovation is variable parametric complexity chosen with an information theoretic criterion. By applying models of different complexity to different branches in the phylogeny, aBSREL delivers statistical performance matching or exceeding best-in-class existing approaches, while running an order of magnitude faster. Based on simulated data analysis, we offer guidelines for what extent and strength of diversifying positive selection can be detected reliably and suggest that there is a natural limit on the optimal parametric complexity for "branch-site" models. An aBSREL analysis of 8,893 Euteleostomes gene alignments demonstrates that over 80% of branches in typical gene phylogenies can be adequately modeled with a single ω ratio model, that is, current models are unnecessarily complicated. However, there are a relatively small number of key branches, whose identities are derived from the data using a model selection procedure, for which it is essential to accurately model evolutionary complexity.
Selection may favor greater investment into sexual ornaments when opportunities for future reproduction are limited, for example, under high adult mortality. However, predation, a key driver of ...mortality, typically selects against elaborate sexual ornaments. Here, we examine the evolution of sexual ornaments in killifishes, which have marked contrasts in life‐history strategy among species and inhabit environments that differ in accessibility to aquatic predators. We first assessed if the size of sexual ornaments (unpaired fins) influenced swimming performance. Second, we investigated whether the evolution of larger ornamental fins is driven primarily by the pace of life‐history (investment into current vs. future reproduction) or habitat type (a proxy for predation risk). We found that larger fins negatively affected swimming performance. Further, males from species inhabiting ephemeral habitats, with lower predation risk, had larger fins and greater sexual dimorphism in fin size, compared to males from more accessible permanent habitats. We show that enlarged ornamental fins, which impair locomotion, evolve more frequently in environments that are less accessible to predators, without clear associations to life‐history strategy. Our results provide a rare link between the evolution of sexual ornaments, effects on locomotion performance, and natural selection on ornament size potentially through habitat differences in predation risk.
The intensity of mating competition varies according to the temporal and spatial distribution of individuals. Measuring sexual dimorphism over time and interpreting the association between ...individuals is therefore important if we aim to understand how sexual traits are influenced. We examined sex differences in the Achala Copper Lizard (Pristidactylus achalensis (Gallardo, 1964)), an endemic species from the highest part of mountains of central Argentina. Over 4 years, we explored sex-specific variation in body size, head size, interlimb length, and body colouration. Furthermore, we evaluated how these traits varied temporally, and we also explored whether the spatial distribution of individuals is explained by variation in these traits. We found that P. achalensis is a species with sexual dimorphism in multiple characters, including body size, head size, and colouration. Interestingly, some traits related to mating, such as head width, show a temporal variability in both sexes, whereas other traits, such as colouration, varies seasonally only in males. Our results underline the intriguing possibility of seasonal morphological changes related to mating, and more broadly that sex differences are influenced by sexual selection pressures mediated by temporal variation in mate competition.
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