Hitchhiking and epistasis give rise to cohort dynamics in adapting populations

Beneficial mutations are the driving force of adaptive evolution. In asexual populations, the identification of beneficial alleles is confounded by the presence of genetically linked hitchhiker mutations. Parallel evolution experiments enable the recognition of common targets of selection; yet these targets are inherently enriched for genes of large target size and mutations of large effect. A comprehensive study of individual mutations is necessary to create a realistic picture of the evolutionarily significant spectrum of beneficial mutations. Here we use a bulk-segregant approach to identify the beneficial mutations across 11 lineages of experimentally evolved yeast populations. We report that nearly 80% of detected mutations have no discernible effects on fitness and less than 1% are deleterious. We determine the distribution of driver and hitchhiker mutations in 31 mutational cohorts, groups of mutations that arise synchronously from low frequency and track tightly with one another. Surprisingly, we find that one-third of cohorts lack identifiable driver mutations. In addition, we identify intracohort synergistic epistasis between alleles of hsl7 and kel1, which arose together in a low-frequency lineage.

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Hitchhiking and epistasis give rise to cohort dynamics in adapting populations

10.1101/106732 ◽

2017 ◽

Cited By ~ 1

Author(s):

Sean W. Buskirk ◽

Ryan Emily Peace ◽

Gregory I. Lang

Keyword(s):

Adaptive Evolution ◽

Driving Force ◽

Parallel Evolution ◽

Low Frequency ◽

Driver Mutations ◽

Sequence Evolution ◽

Beneficial Mutations ◽

Large Target ◽

Asexual Populations ◽

Comprehensive Study

ABSTRACTBeneficial mutations are the driving force of adaptive evolution. In asexual populations, the identification of beneficial alleles is confounded by the presence of genetically-linked hitchhiker mutations. Parallel evolution experiments enable the recognition of common targets of selection, yet these targets are inherently enriched for genes of large target size and mutations of large effect. A comprehensive study of individual mutations is necessary to create a realistic picture of the evolutionarily significant spectrum of beneficial mutations. Here we utilize a bulk-segregant approach to identify the beneficial mutations across 11 lineages of experimentally-evolved yeast populations. We report that most genome sequence evolution is non-adaptive: nearly 80% of detected mutations have no discernable effects on fitness and less than 1% are deleterious. We determine the distribution of driver and hitchhiker mutations in 31 mutational cohorts, groups of up to ten mutations that arise synchronously from low frequency and track tightly with one another. Surprisingly, we find that one-third of cohorts lack identifiable driver mutations. In addition, we identify intra-cohort synergistic epistasis between mutations in hsl7 and kel1, which arose together in a low frequency lineage.

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Comprehensive study of recycling of thermosetting polymer composites – Driving force, challenges and methods

Composites Part B Engineering ◽

10.1016/j.compositesb.2020.108596 ◽

2021 ◽

Vol 207 ◽

pp. 108596

Author(s):

Shubham Utekar ◽

Suriya V K ◽

Neha More ◽

Adarsh Rao

Keyword(s):

Polymer Composites ◽

Driving Force ◽

Thermosetting Polymer ◽

Comprehensive Study

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The Probability of Fixation in Populations of Changing Size

Genetics ◽

10.1093/genetics/146.2.723 ◽

1997 ◽

Vol 146 (2) ◽

pp. 723-733 ◽

Cited By ~ 33

Author(s):

Sarah P Otto ◽

Michael C Whitlock

Keyword(s):

Diffusion Equation ◽

Adaptive Evolution ◽

Process Model ◽

Branching Process ◽

Approximate Solutions ◽

Logistic Growth ◽

Beneficial Mutations ◽

Demographic Models ◽

Deleterious Alleles ◽

Probability Of Fixation

The rate of adaptive evolution of a population ultimately depends on the rate of incorporation of beneficial mutations. Even beneficial mutations may, however, be lost from a population since mutant individuals may, by chance, fail to reproduce. In this paper, we calculate the probability of fixation of beneficial mutations that occur in populations of changing size. We examine a number of demographic models, including a population whose size changes once, a population experiencing exponential growth or decline, one that is experiencing logistic growth or decline, and a population that fluctuates in size. The results are based on a branching process model but are shown to be approximate solutions to the diffusion equation describing changes in the probability of fixation over time. Using the diffusion equation, the probability of fixation of deleterious alleles can also be determined for populations that are changing in size. The results developed in this paper can be used to estimate the fixation flux, defined as the rate at which beneficial alleles fix within a population. The fixation flux measures the rate of adaptive evolution of a population and, as we shall see, depends strongly on changes that occur in population size.

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Does histological assessment accurately distinguish separate primary lung adenocarcinomas from intrapulmonary metastases? A study of paired resected lung nodules in 32 patients using a routine next-generation sequencing panel for driver mutations

Journal of Clinical Pathology ◽

10.1136/jclinpath-2021-207421 ◽

2021 ◽

pp. jclinpath-2021-207421

Author(s):

Frido K Bruehl ◽

Erika E Doxtader ◽

Yu-Wei Cheng ◽

Daniel H Farkas ◽

Carol Farver ◽

...

Keyword(s):

Next Generation Sequencing ◽

Molecular Analysis ◽

Low Frequency ◽

Driver Mutations ◽

Lung Nodules ◽

Driver Gene ◽

Next Generation ◽

Histological Assessment ◽

Lung Adenocarcinomas ◽

Generation Sequencing

AimVarious approaches have been reported for distinguishing separate primary lung adenocarcinomas from intrapulmonary metastases in patients with two lung nodules. The aim of this study was to determine whether histological assessment is reliable and accurate in distinguishing separate primary lung adenocarcinomas from intrapulmonary metastases using routine molecular findings as an adjunct.MethodsWe studied resected tumour pairs from 32 patients with lung adenocarcinomas in different lobes. In 15 of 32 tumour pairs, next-generation sequencing (NGS) for common driver mutations was performed on both nodules. The remainder of tumour pairs underwent limited NGS, or EGFR genotyping. Tumour pairs with different drivers (or one driver/one wild-type) were classified as molecularly unrelated, while those with identical low-frequency drivers were classified as related. Three pathologists independently and blinded to the molecular results categorised tumour pairs as related or unrelated based on histological assessment.ResultsOf 32 pairs, 15 were classified as related by histological assessment, and 17 as unrelated. Of 15 classified as related by histology, 6 were classified as related by molecular analysis, 4 were unrelated and 5 were indeterminate. Of 17 classified as unrelated by histology, 14 were classified as unrelated by molecular analysis, none was related and 3 were indeterminate. Histological assessment of relatedness was inaccurate in 4/32 (12.5%) tumour pairs.ConclusionsA small but significant subset of two-nodule adenocarcinoma pairs is inaccurately judged as related by histological assessment, and can be proven to be unrelated by molecular analysis (driver gene mutations), leading to significant downstaging.

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PATH-40. SPORADIC NF2 WILD-TYPE MULTIPLE MENINGIOMAS HARBOR DISTINCT DRIVER MUTATIONS

Neuro-Oncology ◽

10.1093/neuonc/noab196.492 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi124-vi124

Author(s):

Insa Prilop ◽

Thomas Pinzer ◽

Daniel Cahill ◽

Priscilla Brastianos ◽

Gabriele Schackert ◽

...

Keyword(s):

Hot Spot ◽

Low Frequency ◽

Neurofibromatosis Type ◽

Driver Mutations ◽

Wild Type ◽

Driver Genes ◽

Who Grade ◽

Genetic Changes ◽

Histologic Subtype ◽

Multiple Meningiomas

Abstract OBJECTIVE Multiple meningiomas (MM) are rare and present a unique management challenge. While the mutational landscape of single meningiomas has been extensively studied, understanding the molecular pathogenesis of sporadic MM remains incomplete. The objective of this study is to elucidate the genetic features of sporadic MM. METHODS We identified nine patients with MM (n=19) defined as ≥2 spatially separated synchronous or metachronous meningiomas. We profiled genetic changes in these tumors using next-generation sequencing (NGS) assay that covers a large number of targetable and frequently mutated genes in meningiomas including AKT1, KLF4, NF2, PIK3CA/PIK3R1, POLR2A, SMARCB1, SMO, SUFU, TRAF7, and the TERT promoter. RESULTS Most of MM were WHO grade 1 (n= 16, 84.2%). Within individual patients, no driver mutation was shared between separate tumors. All but two cases harbored different hot spot mutations in known meningioma-driver genes like TRAF7 (n= 5), PIK3CA (n= 4), AKT1 (n= 3), POLR2A (n=1) and SMO (n= 1). Moreover, individual tumors differed in histologic subtype in 8/9 patients. The low frequency of NF2 mutations in our series stands in contrast to previous studies that included hereditary cases arising in the setting of neurofibromatosis type 2 (NF2). CONCLUSIONS Our findings provide evidence for genomic inter-tumor heterogeneity and an independent molecular origin of sporadic NF2 wild-type MM. Furthermore, these findings suggest that genetic characterization of each lesion is warranted in sporadic MM.

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Radio Spectra and Particle Ages of the Head-Tail Radio Galaxy NGC1265

Symposium - International Astronomical Union ◽

10.1017/s0074180900081055 ◽

1996 ◽

Vol 175 ◽

pp. 347-348

Author(s):

L. Feretti ◽

G. Giovannini ◽

U. Klein ◽

K.-H. Mack ◽

L.G. Sijbring

Keyword(s):

Magnetic Field ◽

Radio Galaxy ◽

Low Frequency ◽

Radio Galaxies ◽

Field Structure ◽

Magnetic Field Structure ◽

Linearly Polarized ◽

Faraday Effects ◽

Perseus Cluster ◽

Comprehensive Study

We have performed sensitive observations of three classical head-tail radio galaxies at λ11.1, 6.3, and 2.8 cm using the Effelsberg 100-m telescope (Zech, 1994). Complete maps of the sources 3C129, NGC1265, and 3C465 were obtained, including the distributions of the linearly polarized intensity. Together with the low-frequency interferometric maps these allow a comprehensive study of their radio spectra and, based on models of particle losses, the derivations of particle ages across these sources. The highest frequency involved allows an unambiguous derivation of the projected magnetic field structure, unimpeded by Faraday effects. Here we focus on NGC1265, which is located in the Perseus Cluster.

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Evolutionary stalling and a limit on the power of natural selection to improve a cellular module

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1921881117 ◽

2020 ◽

Vol 117 (31) ◽

pp. 18582-18590 ◽

Cited By ~ 2

Author(s):

Sandeep Venkataram ◽

Ross Monasky ◽

Shohreh H. Sikaroodi ◽

Sergey Kryazhimskiy ◽

Betul Kacar

Keyword(s):

Escherichia Coli ◽

Natural Selection ◽

Adaptive Evolution ◽

Genetic Load ◽

Performance Theory ◽

Biological Functions ◽

Beneficial Mutations ◽

Translation Machinery ◽

Adaptive Mutations ◽

Organismal Fitness

Cells consist of molecular modules which perform vital biological functions. Cellular modules are key units of adaptive evolution because organismal fitness depends on their performance. Theory shows that in rapidly evolving populations, such as those of many microbes, adaptation is driven primarily by common beneficial mutations with large effects, while other mutations behave as if they are effectively neutral. As a consequence, if a module can be improved only by rare and/or weak beneficial mutations, its adaptive evolution would stall. However, such evolutionary stalling has not been empirically demonstrated, and it is unclear to what extent stalling may limit the power of natural selection to improve modules. Here we empirically characterize how natural selection improves the translation machinery (TM), an essential cellular module. We experimentally evolved populations ofEscherichia coliwith genetically perturbed TMs for 1,000 generations. Populations with severe TM defects initially adapted via mutations in the TM, but TM adaptation stalled within about 300 generations. We estimate that the genetic load in our populations incurred by residual TM defects ranges from 0.5 to 19%. Finally, we found evidence that both epistasis and the depletion of the pool of beneficial mutations contributed to evolutionary stalling. Our results suggest that cellular modules may not be fully optimized by natural selection despite the availability of adaptive mutations.

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