The neutral theory of molecular evolution predicts that the amount of neutral polymorphisms within a species will increase proportionally with the census population size (Nc). However, this ...prediction has not been borne out in practice: while the range of Nc spans many orders of magnitude, levels of genetic diversity within species fall in a comparatively narrow range. Although theoretical arguments have invoked the increased efficacy of natural selection in larger populations to explain this discrepancy, few direct empirical tests of this hypothesis have been conducted. In this work, we provide a direct test of this hypothesis using population genomic data from a wide range of taxonomically diverse species. To do this, we relied on the fact that the impact of natural selection on linked neutral diversity depends on the local recombinational environment. In regions of relatively low recombination, selected variants affect more neutral sites through linkage, and the resulting correlation between recombination and polymorphism allows a quantitative assessment of the magnitude of the impact of selection on linked neutral diversity. By comparing whole genome polymorphism data and genetic maps using a coalescent modeling framework, we estimate the degree to which natural selection reduces linked neutral diversity for 40 species of obligately sexual eukaryotes. We then show that the magnitude of the impact of natural selection is positively correlated with Nc, based on body size and species range as proxies for census population size. These results demonstrate that natural selection removes more variation at linked neutral sites in species with large Nc than those with small Nc and provides direct empirical evidence that natural selection constrains levels of neutral genetic diversity across many species. This implies that natural selection may provide an explanation for this longstanding paradox of population genetics.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gregor Mendel was an Augustinian priest in the Monastery of St. Thomas in Brünn (Brno, Czech Republic) as well as a civilian employee who taught natural history and physics in the Brünn Modern ...School. The monastery's secular function was to provide teachers for the public schools across Moravia. It was a cultural, educational, and artistic center with an elite core of friar-teachers with a well-stocked library and other amenities including a gourmet kitchen. It was wealthy, with far-flung holdings yielding income from agricultural productions. Mendel had failed his tryout as a parish priest and did not complete his examination for teaching certification despite 2 y of study at the University of Vienna. In addition to his teaching and religious obligations, Mendel carried out daily meteorological and astronomical observations, cared for the monastery's fruit orchard and beehives, and tended plants in the greenhouse and small outdoor gardens. In the years 1856 to 1863, he carried out experiments on heredity of traits in garden peas regarded as revolutionary today but not widely recognized during his lifetime and until 16 y after his death. In 1868 he was elected abbot of the monastery, a significantly elevated position in the ecclesiastical and civil hierarchy. While he had hoped to be elected, and was honored to accept, he severely underestimated its administrative responsibilities and gradually had to abandon his scientific interests. The last decade of his life was marred by an ugly dispute with civil authorities over monastery taxation.
Antibiotic resistance can evolve through the sequential accumulation of multiple mutations. To study such gradual evolution, we developed a selection device, the 'morbidostat', that continuously ...monitors bacterial growth and dynamically regulates drug concentrations, such that the evolving population is constantly challenged. We analyzed the evolution of resistance in Escherichia coli under selection with single drugs, including chloramphenicol, doxycycline and trimethoprim. Over a period of ∼20 days, resistance levels increased dramatically, with parallel populations showing similar phenotypic trajectories. Whole-genome sequencing of the evolved strains identified mutations both specific to resistance to a particular drug and shared in resistance to multiple drugs. Chloramphenicol and doxycycline resistance evolved smoothly through diverse combinations of mutations in genes involved in translation, transcription and transport. In contrast, trimethoprim resistance evolved in a stepwise manner, through mutations restricted to the gene encoding the enzyme dihydrofolate reductase (DHFR). Sequencing of DHFR over the time course of the experiment showed that parallel populations evolved similar mutations and acquired them in a similar order.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Chromosomal inversions have been an enduring interest of population geneticists since their discovery in Drosophila melanogaster. Numerous lines of evidence suggest powerful selective pressures ...govern the distributions of polymorphic inversions, and these observations have spurred the development of many explanatory models. However, due to a paucity of nucleotide data, little progress has been made towards investigating selective hypotheses or towards inferring the genealogical histories of inversions, which can inform models of inversion evolution and suggest selective mechanisms. Here, we utilize population genomic data to address persisting gaps in our knowledge of D. melanogaster's inversions. We develop a method, termed Reference-Assisted Reassembly, to assemble unbiased, highly accurate sequences near inversion breakpoints, which we use to estimate the age and the geographic origins of polymorphic inversions. We find that inversions are young, and most are African in origin, which is consistent with the demography of the species. The data suggest that inversions interact with polymorphism not only in breakpoint regions but also chromosome-wide. Inversions remain differentiated at low levels from standard haplotypes even in regions that are distant from breakpoints. Although genetic exchange appears fairly extensive, we identify numerous regions that are qualitatively consistent with selective hypotheses. Finally, we show that In(1)Be, which we estimate to be ∼60 years old (95% CI 5.9 to 372.8 years), has likely achieved high frequency via sex-ratio segregation distortion in males. With deeper sampling, it will be possible to build on our inferences of inversion histories to rigorously test selective models-particularly those that postulate that inversions achieve a selective advantage through the maintenance of co-adapted allele complexes.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Genetics Society of America's Thomas Hunt Morgan Medal honors researchers for lifetime achievement in genetics. The recipient of the 2019 Morgan Medal is Daniel Hartl of Harvard University, who ...is recognized for his influential and diverse contributions to genetics research. The unifying theme of Hartl's broad impacts on transmission, population, evolutionary, and medical genetics has been the combination of theoretical insights with cutting-edge experimental techniques. Some of his contributions include revealing the genetics of segregation distortion, developing statistical frameworks for estimating the effects of selection, application of these frameworks to natural and experimental populations, discovery of the
transposon and its influence on genome evolution, insights into the evolution of gene expression differences, and modeling the evolution of malaria parasite populations. Hartl is also known as a supportive mentor who has trained many prominent geneticists that continue to shape the field.
Genes encode components of coevolved and interconnected networks. The effect of genotype on phenotype therefore depends on genotypic context through gene interactions known as epistasis. Epistasis is ...important in predicting phenotype from genotype for an individual. It is also examined in population studies to identify genetic risk factors in complex traits and to predict evolution under selection. Paradoxically, the effects of genotypic context in individuals and populations are distinct and sometimes contradictory. We argue that predicting genotype from phenotype for individuals based on population studies is difficult and, especially in human genetics, likely to result in underestimating the effects of genotypic context.
The effect of a particular mutation frequently depends on what other variants are present in the genome. Genetic epistasis is readily apparent in laboratory organisms. Why hasn’t it turned up as a major factor in studies of human genetics and disease risk?
Five point mutations in a particular {szligbeta}-lactamase allele jointly increase bacterial resistance to a clinically important antibiotic by a factor of approximately100,000. In principle, ...evolution to this high-resistance {szligbeta}-lactamase might follow any of the 120 mutational trajectories linking these alleles. However, we demonstrate that 102 trajectories are inaccessible to Darwinian selection and that many of the remaining trajectories have negligible probabilities of realization, because four of these five mutations fail to increase drug resistance in some combinations. Pervasive biophysical pleiotropy within the {szligbeta}-lactamase seems to be responsible, and because such pleiotropy appears to be a general property of missense mutations, we conclude that much protein evolution will be similarly constrained. This implies that the protein tape of life may be largely reproducible and even predictable.
Highlights • Fitness landscapes can help in understanding constraints on evolutionary change. • Combinatorially complete data sets reveal patterns of higher-order fitness interactions. • Actual ...fitness landscapes are much smoother than random fitness landscapes. • Reciprocal sign epistasis can occur but is not pervasive. • Fitness landscapes open great opportunities for further research.
The evolution of transcriptional regulatory networks entails the expansion and diversification of transcription factor (TF) families. The forkhead family of TFs, defined by a highly conserved winged ...helix DNA-binding domain (DBD), has diverged into dozens of subfamilies in animals, fungi, and related protists. We have used a combination of maximum-likelihood phylogenetic inference and independent, comprehensive functional assays of DNA-binding capacity to explore the evolution of DNA-binding specificity within the forkhead family. We present converging evidence that similar alternative sequence preferences have arisen repeatedly and independently in the course of forkhead evolution. The vast majority of DNA-binding specificity changes we observed are not explained by alterations in the known DNA-contacting amino acid residues conferring specificity for canonical forkhead binding sites. Intriguingly, we have found forkhead DBDs that retain the ability to bind very specifically to two completely distinct DNA sequence motifs. We propose an alternate specificity-determining mechanism whereby conformational rearrangements of the DBD broaden the spectrum of sequence motifs that a TF can recognize. DNA-binding bispecificity suggests a previously undescribed source of modularity and flexibility in gene regulation and may play an important role in the evolution of transcriptional regulatory networks.
It is generally assumed that stabilizing selection promoting a phenotypic optimum acts to shape variation in quantitative traits across individuals and species. Although gene expression represents an ...intensively studied molecular phenotype, the extent to which stabilizing selection limits divergence in gene expression remains contentious. In this study, we present a theoretical framework for the study of stabilizing and directional selection using data from between-species divergence of continuous traits. This framework, based upon Brownian motion, is analytically tractable and can be used in maximum-likelihood or Bayesian parameter estimation. We apply this model to gene-expression levels in 7 species of Drosophila, and find that gene-expression divergence is substantially curtailed by stabilizing selection. However, we estimate the selective effect, s, of gene-expression change to be very small, approximately equal to Ns for a change of one standard deviation, where N is the effective population size. These findings highlight the power of natural selection to shape phenotype, even when the fitness effects of mutations are in the nearly neutral range.
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