adaptive mutations
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2022 ◽  
Author(s):  
Melanie Bernette Abrams ◽  
Rachel B Brem

Many traits of industrial and basic biological interest arose long ago, and manifest now as fixed differences between a focal species and its reproductively isolated relatives. In these systems, extant individuals can hold clues to the mechanisms by which phenotypes evolved in their ancestors. We harnessed yeast thermotolerance as a test case for such molecular-genetic inferences. In viability experiments, we showed that extant Saccharomyces cerevisiae survived at temperatures where cultures of its sister species S. paradoxus died out. Then, focusing on loci that contribute to this difference, we found that the genetic mechanisms of high-temperature growth changed with temperature. We also uncovered a robust signature of positive selection at thermotolerance loci in S. cerevisiae population sequences. We interpret these results in light of a model of gradual acquisition of thermotolerance in the S. cerevisiae lineage along a temperature cline. We propose that in an ancestral S. cerevisiae population, alleles conferring defects at a given temperature would have been resolved by adaptive mutations, expanding the range and setting the stage for further temperature advances. Together, our results and interpretation underscore the power of genetic approaches to explore how an ancient trait came to be.


Biology ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 91
Author(s):  
Qingxiang Guo ◽  
Christopher M. Whipps ◽  
Yanhua Zhai ◽  
Dan Li ◽  
Zemao Gu

Nematocysts are secretory organelles in cnidarians that play important roles in predation, defense, locomotion, and host invasion. However, the extent to which nematocysts contribute to adaptation and the mechanisms underlying nematocyst evolution are unclear. Here, we investigated the role of the nematocyst in cnidarian evolution based on eight nematocyst proteomes and 110 cnidarian transcriptomes/genomes. We detected extensive species-specific adaptive mutations in nematocyst proteins (NEMs) and evidence for decentralized evolution, in which most evolutionary events involved non-core NEMs, reflecting the rapid diversification of NEMs in cnidarians. Moreover, there was a 33–55 million year macroevolutionary lag between nematocyst evolution and the main phases of cnidarian diversification, suggesting that the nematocyst can act as a driving force in evolution. Quantitative analysis revealed an excess of adaptive changes in NEMs and enrichment for positively selected conserved NEMs. Together, these findings suggest that nematocysts may be key to the adaptive success of cnidarians and provide a reference for quantitative analyses of the roles of phenotypic novelties in adaptation.


2021 ◽  
Vol 1 ◽  
Author(s):  
James Z. Curlin ◽  
Kimberly Schmitt ◽  
Leila Remling-Mulder ◽  
Ryan V. Moriarty ◽  
John J. Baczenas ◽  
...  

Simian immunodeficiency virus native to sooty mangabeys (SIVsm) is believed to have given rise to HIV-2 through cross-species transmission and evolution in the human. SIVmac239 and SIVB670, pathogenic to macaques, and SIVhu, isolated from an accidental human infection, also have origins in SIVsm. With their common ancestral lineage as that of HIV-2 from the progenitor SIVsm, but with different passage history in different hosts, they provide a unique opportunity to evaluate cross-species transmission to a new host and their adaptation/evolution both in terms of potential genetic and phenotypic changes. Using humanized mice with a transplanted human system, we evaluated in vivo replication kinetics, CD4+ T cell dynamics and genetic adaptive changes during serial passage with a goal to understand their evolution under human selective immune pressure. All the three viruses readily infected hu-mice causing chronic viremia. While SIVmac and SIVB670 caused CD4+ T cell depletion during sequential passaging, SIVhu with a deletion in nef gene was found to be less pathogenic. Deep sequencing of the genomes of these viruses isolated at different times revealed numerous adaptive mutations of significance that increased in frequency during sequential passages. The ability of these viruses to infect and replicate in humanized mice provides a new small animal model to study SIVs in vivo in addition to more expensive macaques. Since SIVmac and related viruses have been indispensable in many areas of HIV pathogenesis, therapeutics and cure research, availability of this small animal hu-mouse model that is susceptible to both SIV and HIV viruses is likely to open novel avenues of investigation for comparative studies using the same host.


2021 ◽  
Vol 5 (4) ◽  
pp. e202101333
Author(s):  
Xudong Zou ◽  
Bernhard Schaefke ◽  
Yisheng Li ◽  
Fujian Jia ◽  
Wei Sun ◽  
...  

Alternative splicing is ubiquitous, but the mechanisms underlying its pattern of evolutionary divergence across mammalian tissues are still underexplored. Here, we investigated the cis-regulatory divergences and their relationship with tissue-dependent trans-regulation in multiple tissues of an F1 hybrid between two mouse species. Large splicing changes between tissues are highly conserved and likely reflect functional tissue-dependent regulation. In particular, micro-exons frequently exhibit this pattern with high inclusion levels in the brain. Cis-divergence of splicing appears to be largely non-adaptive. Although divergence is in general associated with higher densities of sequence variants in regulatory regions, events with high usage of the dominant isoform apparently tolerate more mutations, explaining why their exon sequences are highly conserved but their intronic splicing site flanking regions are not. Moreover, we demonstrate that non-adaptive mutations are often masked in tissues where accurate splicing likely is more important, and experimentally attribute such buffering effect to trans-regulatory splicing efficiency.


2021 ◽  
Author(s):  
Paul Jay ◽  
Manon Leroy ◽  
Yann Le Poul ◽  
Annabel Whibley ◽  
Monica Arias ◽  
...  

Supergenes are genetic architectures associated with discrete and concerted variation in multiple traits. It has long been suggested that supergenes control these complex polymorphisms by suppressing recombination between set of coadapted genes. However, because recombination suppression hinders the dissociation of the individual effects of genes within supergenes, there is still little evidence that supergenes evolve by tightening linkage between coadapted genes. Here, combining an landmark-free phenotyping algorithm with multivariate genome wide association studies, we dissected the genetic basis of wing pattern variation in the butterfly Heliconius numata. We showed that the supergene controlling the striking wing-pattern polymorphism displayed by this species contains many independent loci associated with different features of wing patterns. The three chromosomal inversions of this supergene suppress recombination between these loci, supporting the hypothesis that they may have evolved because they captured beneficial combinations of alleles. Some of these loci are associated with colour variations only in morphs controlled by inversions, indicating that they were recruited after the formation of these inversions. Our study shows that supergenes and clusters of adaptive loci in general may form via the evolution of chromosomal rearrangements suppressing recombination between co-adapted loci but also via the subsequent recruitment of linked adaptive mutations.


2021 ◽  
Author(s):  
Stefan Kusch ◽  
Lamprinos Frantzeskakis ◽  
Birthe D. Lassen ◽  
Florian Kümmel ◽  
Lina Pesch ◽  
...  

Hosts and pathogens typically engage in an evolutionary arms race. This also applies to phytopathogenic powdery mildew fungi, which can rapidly overcome plant resistance and perform host jumps. Using experimental evolution, we show that the powdery mildew pathogen Blumeria graminis f.sp. hordei is capable of breaking the agriculturally important broad-spectrum resistance conditioned by barley loss-of-function mlo mutants. Partial mlo virulence is associated with a distinctive pattern of adaptive mutations, including small-sized (8-40 kb) deletions, one of which likely affects spore morphology. The detected mutational spectrum comprises the same loci in at least two independent mlo-virulent isolates, indicating convergent multigenic evolution. This work highlights the dynamic genome evolution of an obligate biotrophic plant pathogen with a transposon-enriched genome.


Author(s):  
Victoria Divino ◽  
Vamshi Ruthwik Anupindi ◽  
Mitch DeKoven ◽  
Joaquin Mould-Quevedo ◽  
Stephen I Pelton ◽  
...  

Abstract Background Cell-derived influenza vaccines are not subject to egg adaptive mutations that have potential to decrease vaccine effectiveness. This retrospective analysis estimated the relative vaccine effectiveness (rVE) of cell-derived quadrivalent influenza vaccine (IIV4c) compared to standard egg-derived quadrivalent influenza vaccines (IIV4e) among recipients aged 4-64 years in the US during the 2019-20 influenza season. Methods The IQVIA PharMetrics® Plus administrative claims database was utilized. Study outcomes were assessed post-vaccination through the end of the study period (March 7, 2020). Inverse probability of treatment weighting (IPTW) was implemented to adjust for covariate imbalance. Adjusted rVE against influenza-related hospitalizations/emergency room (ER) visits and other clinical outcomes was estimated through IPTW-weighted Poisson regression models for the IIV4c and IIV4e cohorts and for the subgroup with ≥1 high-risk condition. Sensitivity analyses modifying the outcome assessment period as well as a doubly-robust analysis were also conducted. IPTW-weighted generalized linear models were used to estimate predicted annualized all-cause costs. Results The final sample comprised 1,138,969 IIV4c and 3,926,357 IIV4e recipients following IPTW adjustment. IIV4c was more effective in preventing influenza-related hospitalizations/ER visits as well as respiratory-related hospitalizations/ER visits compared to IIV4e. IIV4c was also more effective for the high-risk subgroup and across the sensitivity analyses. IIV4c was also associated with significantly lower annualized all-cause total costs compared to IIV4e (-$467), driven by lower costs for outpatient medical services and inpatient hospitalizations. Conclusions IIV4c was significantly more effective in preventing influenza-related hospitalizations/ER visits compared to IIV4e and was associated with significantly lower all-cause costs.


2021 ◽  
Author(s):  
Santosh Kumar ◽  
Valid Gahramanov ◽  
Julia Yaglom ◽  
Shivani Patel ◽  
Lukasz Kaczmarczyk ◽  
...  

The selection of drug-resistant mammalian cell mutants requires multiple drug exposures. When cloned genetically identical cells are exposed to the drug, resistance is unlikely to result from the selection of pre-existent mutations. Therefore, adaptation must involve the generation of drug-resistant mutations de-novo. Understanding how adaptive mutations are generated and protect cells is important for our knowledge of cancer biology and evolution. Here, we studied the adaptation of cancer cells to topoisomerase (Top1) inhibitor irinotecan, which triggers DNA breaks, resulting in cytotoxicity. The resistance mechanism was based on the gradual accumulation of hundreds of thousands of recurrent mutations in non-coding DNA at sequence-specific Top1 cleavage sites. Repair of DSBs at these sites following initial irinotecan exposures created mutant sequences that were resistant to further Top1 cleavage. Therefore, by creating DNA breaks Top1 increases the rate of highly protective mutations specifically at such spots, thus explaining a puzzling need of dose escalation in resistance development.


Nanomaterials ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3118
Author(s):  
Marcelly Chue-Gonçalves ◽  
Giovana N. Pereira ◽  
Lígia C. Faccin-Galhardi ◽  
Renata K. T. Kobayashi ◽  
Gerson Nakazato

In view of the current Coronavirus Disease 2019 (COVID-19) pandemic outbreak, the research community is focusing on development of diagnostics, treatment, and vaccines to halt or reverse this scenario. Although there are already various vaccines available, adaptive mutations in the SARS-CoV-2 genome can alter its pathogenic potential and, at the same time, increase the difficulty of developing drugs or immunization by vaccines. Nanotechnology carries a potential to act in all stages in fighting this viral disease, with several possibilities of strategies such as applying nanoparticles directly as antivirals in delivery systems against these viruses or incorporating them in materials, with power of achievement in therapeutics, vaccines and prevention. In this paper, we review and bring insights of recent studies using metal nanocomposites as antivirals against coronavirus and structurally similar viruses.


2021 ◽  
Author(s):  
Muhammad Ikram Anwar ◽  
Ni Li ◽  
Qing Zhou ◽  
Mingxiao Chen ◽  
Chengguang Hu ◽  
...  

Abstract Background: Hepatitis C virus (HCV) is an important human pathogen causing chronic hepatitis C, end-stage liver diseases, and hepatocellular carcinoma. The development of infectious HCV cell culture systems primarily relied on the replication enhancement effect of adaptive mutations. Although the mode of action may vary, those adaptive mutations could direct the study of virus-host interactions required for efficient virus infection. We previously identified a substitution D559G in NS5B (RNA dependent RNA polymerase) critical for the replication of HCV genomes. In this study, we set out to study whether D559G-NS5B specifically interacted with some host factors crucial for HCV infection.Methods: Through mass spectrometry analysis of immunoprecipitation mixture of ectopically expressed wild-type and D559G-mutated NS5B, we identified candidate factors showing potential interactions with NS5B and D559G-NS5B. The requirement of selected host factor in HCV infection in vitro was demonstrated by gene knockout, overexpression, virus infection, and co-immunoprecipitation approaches.Results: From the results of immunoprecipitation and mass spectrometry analysis, we selected protein phosphatase 2 regulatory subunit B’delta (PPP2R5D) for further characterization. Co-immunoprecipitation confirmed that both wild-type and D559G NS5B proteins interacted with PPP2R5D, but the interaction between D559G-NS5B and PPP2R5D was more efficient. Silencing of PPP2R5D decreased HCV infection, and knockout of PPP2R5D nearly eliminated HCV infection in Huh7.5 cells. Transient and stably overexpression of PPP2R5D in PPP2R5D-knockout cells restored HCV infection to a level close to that seen for wild-type Huh7.5 cells. Conclusions: PPP2R5D is required for HCV infection in cultured hepatoma cells, and PPP2R5D may function through binding to HCV NS5B. The underlying mechanism of PPP2R5D in the complete HCV life cycle requires further investigation.


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