scholarly journals Evolution of linkage and genome expansion in protocells

2019 ◽  
Author(s):  
András Szilágyi ◽  
Viktor Péter Kovács ◽  
Eörs Szathmáry ◽  
Mauro Santos
Keyword(s):  
Marked Reduction ◽  
Genetic Linkage ◽  
Deleterious Mutations ◽  
Remarkable Feature ◽  
Intragenomic Conflict ◽  
Size Number ◽  
Added Benefit ◽  
Chromosome Formation ◽  
Selection Of ◽  
Chromosome Level

AbstractChromosomes are likely to have followed unlinked genes in early evolution. Genetic linkage reduces the assortment load and intragenomic conflict in reproducing protocell models to the extent that chromosomes can go to fixation even if chromosomes suffer from a replicative disadvantage, relative to unlinked genes, proportional to their length. Here we show that chromosomes spread within protocells even if recurrent deleterious mutations affecting replicating genes (as ribozymes) are taken into account. Dosage effect selects for optimal genomic composition within protocells that carries over to the genic composition of emerging chromosomes. Lacking an accurate segregation mechanism protocells continue to benefit from the stochastic corrector principle (group selection of early replicators), but now at the chromosome level. A remarkable feature of this process is the appearance of multigene families (in optimal genic proportions) on chromosomes. An added benefit of chromosome formation is an increase in the selectively maintainable genome size (number of different genes), primarily due to the marked reduction of the assortment load. This result complements the established benefit conferred by chromosomes on protocells allowing for the fixation of highly specific and efficient enzymes.

scholarly journals Evolution of linkage and genome expansion in protocells: The origin of chromosomes

PLoS Genetics ◽  
2020 ◽  
Vol 16 (10) ◽  
pp. e1009155
Author(s):  
András Szilágyi ◽  
Viktor Péter Kovács ◽  
Eörs Szathmáry ◽  
Mauro Santos
Keyword(s):  
Genome Size ◽  
Marked Reduction ◽  
Deleterious Mutations ◽  
Remarkable Feature ◽  
Intragenomic Conflict ◽  
Size Number ◽  
Added Benefit ◽  
Chromosome Formation ◽  
Selection Of ◽  
Chromosome Level

Chromosomes are likely to have assembled from unlinked genes in early evolution. Genetic linkage reduces the assortment load and intragenomic conflict in reproducing protocell models to the extent that chromosomes can go to fixation even if chromosomes suffer from a replicative disadvantage, relative to unlinked genes, proportional to their length. Here we numerically show that chromosomes spread within protocells even if recurrent deleterious mutations affecting replicating genes (as ribozymes) are considered. Dosage effect selects for optimal genomic composition within protocells that carries over to the genic composition of emerging chromosomes. Lacking an accurate segregation mechanism, protocells continue to benefit from the stochastic corrector principle (group selection of early replicators), but now at the chromosome level. A remarkable feature of this process is the appearance of multigene families (in optimal genic proportions) on chromosomes. An added benefit of chromosome formation is an increase in the selectively maintainable genome size (number of different genes), primarily due to the marked reduction of the assortment load. The establishment of chromosomes is under strong positive selection in protocells harboring unlinked genes. The error threshold of replication is raised to higher genome size by linkage due to the fact that deleterious mutations affecting protocells metabolism (hence fitness) show antagonistic (diminishing return) epistasis. This result strengthens the established benefit conferred by chromosomes on protocells allowing for the fixation of highly specific and efficient enzymes.

scholarly journals Dual symbiosis in the deep-sea hydrothermal vent snail Gigantopelta aegis revealed by its hologenome

2020 ◽  
Author(s):  
Yi Lan ◽  
Jin Sun ◽  
Chong Chen ◽  
Yanan Sun ◽  
Yadong Zhou ◽  
...  
Keyword(s):  
Deep Sea ◽  
Hydrothermal Vent ◽  
Hydrothermal Vents ◽  
Snail Host ◽  
Bacterial Symbionts ◽  
Mutualistic Relationship ◽  
Genomic Studies ◽  
Similar Depth ◽  
Selection Of ◽  
Chromosome Level

AbstractAnimals endemic to deep-sea hydrothermal vents often form obligatory relationships with bacterial symbionts, maintained by intricate host-symbiont interactions. Endosymbiosis with more than one symbiont is uncommon, and most genomic studies focusing on such ‘dual symbiosis’ systems have not investigated the host and the symbionts to a similar depth simultaneously. Here, we report a novel dual symbiosis among the peltospirid snail Gigantopelta aegis and its two Gammaproteobacteria endosymbionts – one being a sulphur oxidiser and the other a methane oxidiser. We assembled high-quality genomes for all three parties of this holobiont, with a chromosome-level assembly for the snail host (1.15 Gb, N50 = 82 Mb, 15 pseudo-chromosomes). In-depth analyses of these genomes reveal an intimate mutualistic relationship with complementarity in nutrition and metabolic codependency, resulting in a system highly versatile in transportation and utilisation of chemical energy. Moreover, G. aegis has an enhanced immune capability that likely facilitates the possession of more than one type of symbiont. Comparisons with Chrysomallon squamiferum, another chemosymbiotic snail in the same family but only with one sulphur-oxidising endosymbiont, show that the two snails’ sulphur-oxidising endosymbionts are phylogenetically distant, agreeing with previous results that the two snails have evolved endosymbiosis independently and convergently. Notably, the same capabilities of biosynthesis of specific nutrition lacking in the host genome are shared by the two sulphur-oxidising endosymbionts of the two snail genera, which may be a key criterion in the selection of symbionts by the hosts.

scholarly journals Antibiotic usage rates in bacterial versus nonbacterial diseases: a new way to monitor hospital-acquired infections in children: a retrospective case analysis

2020 ◽  
Vol 7 (11) ◽  
pp. 2176
Author(s):  
Jayendra R. Gohil ◽  
Chintu C. Chaudary ◽  
Sheena D. Sivanandan
Keyword(s):  
Antibiotic Usage ◽  
Retrospective Case ◽  
Hospital Acquired Infections ◽  
Group A ◽  
Added Benefit ◽  
Reduction Of Mortality ◽  
Group B ◽  
The Cost ◽  
Hospital Acquired ◽  
Selection Of

Background: While treating children, the selection of antibiotics, when indicated, should be from the point of its effectiveness, safety, suitability, and cost. However, this flow of action does not take place in all cases. Aim of the study was to assess the antibiotic usage in admitted children and mortality.Methods: The case records between January to July 2012 in children wards was evaluated for the use of antibiotics. Patients were grouped into; group A- ‘must use' antibiotic in all, and group B- where antibiotics are not indicated.Results: There were 1852 admissions, including 719 Thalassemia cases. Antibiotic usage was 63% in 1133 cases after excluding thalassemia. Out of 1133 cases, 423 were in group A and 710 cases were in group B. In group B the antibiotic usage was 41%. The mortality was 6.6% and 4.8% in group A and B. Inside group B, mortality was 5.9% versus 4.0% in those administered versus not administered, antibiotics.Conclusions: There was no increase in mortality in patients in whom antibiotics were not prescribed, and no added benefit of prescribing antibiotics was observed in nonbacterial group B disease patients. The mortality was similar in both the groups. In nonbacterial group B, the antibiotics did not offer any advantage in the reduction of mortality, but increased the cost of the treatment, and possibly the chance of development of drug resistance and adverse events. When analysing the hospital antibiotic usage, only the nonbacterial diseases should be considered to get a true picture of the inappropriate prescription of antibiotics.

scholarly journals  Molecular markers: their use in tree improvement

2012 ◽  
Vol 58 (No. 3) ◽  
pp. 137-144 ◽  
Author(s):  
R. Mahajan ◽  
P. Gupta
Keyword(s):  
Molecular Markers ◽  
Tree Species ◽  
Cell Biology ◽  
Genetic Linkage ◽  
Morphological Characteristics ◽  
Phenotypic Selection ◽  
Tree Improvement ◽  
Linkage Maps ◽  
Genetic Linkage Maps ◽  
Selection Of

Earlier breeders used phenotypic selection based on morphological characteristics to improve tree varieties. These selections often take many cycles of breeding and backcrossing in order to place desired characteristics. But today the knowledge has paved the way for a much deeper understanding of the mechanics of cell biology and the hereditary process itself. Breeders are presented with numerous possibilities of altering the behaviour of existing varieties. Linkage between molecular markers can be translated to genetic linkage maps, which have become an important tool in plant genetics. They may choose to use marker-assisted approaches in order to facilitate the selection of favourable combinations of genes that occur naturally within a tree species.  

Selection of flood-resistant and susceptible seedlings of Populustrichocarpa Torr. & Gray

1988 ◽  
Vol 18 (2) ◽  
pp. 271-275 ◽  
Author(s):  
Barbara A. Smit
Keyword(s):  
Leaf Area ◽  
Marked Reduction ◽  
Branch Length ◽  
Stomatal Resistance ◽  
Growth And Survival ◽  
Seed Collection ◽  
Individual Leaf ◽  
Total Branch Length ◽  
Collection Sites ◽  
Selection Of

To identify Populustrichocarpa plants with contrasting levels of resistance to flooding, seedlings from five diverse riparian sites were evaluated for growth and survival under flooding conditions. All seedlings survived 6 or 8 weeks of flooding. Total branch length and leaf number were reduced in all flooded plants relative to nonflooded controls. There was also a marked reduction in individual leaf area and increased stomatal resistance of flooded plants compared with nonflooded controls. Growth of flooded and nonflooded plants was highly variable within populations and no significant trends were found among populations. Therefore differential responses to flooding can be selected for within any of the seed collection sites. Plants that were rated as particularly resistant or susceptible fo flooding were selected for further study.

Clinical correlates of response to anti-PD-1 (aPD1)-based therapy in patients (pts) with metastatic melanoma (MM).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21000-e21000
Author(s):  
Elizabeth J. Davis ◽  
Shilin Zhao ◽  
Fei Ye ◽  
Katherine Rappazzo ◽  
Jeffrey Alan Sosman ◽  
...  
Keyword(s):  
Performance Status ◽  
Progression Free Survival ◽  
Clinical Predictors ◽  
Ecog Performance Status ◽  
Free Survival ◽  
Size Number ◽  
Multivariable Analyses ◽  
Status Number ◽  
Univariate Analyses ◽  
Selection Of

e21000 Background: aPD1, alone or in combination with ipilimumab (IPI), produces durable responses in a subset of MM. Tumor features that correlate with treatment response, including size, number, and location of metastases (mets) are not well defined. Methods: We collected clinical data from mm pts treated at one center who received aPD1 (n = 185) or aPD1 + IPI (n = 42). We correlated number of mets, size of largest tumor, and organ involvement with response rate (RR), progression-free survival (PFS) and overall survival (OS). Results: Among all pts, RR was 67% for aPD1 + IPI and 41% for aPD1 alone. In univariate analyses, responders to aPD1 had lower diameter of largest tumor (4cm vs. 5.5cm; p = 0.02) whereas aPD1 + IPI had equivalent largest tumor diameters (p = 0.65). Regarding sites of mets, liver mets were associated with lower RR in aPD1 treated pts (26% vs. 46%), lower PFS (median 138 vs. 326 days, p = 0.02), and lower OS (median 334 vs. 1080 days, p < 0.01). No associations with RR, PFS, or OS were observed with liver mets in aPD1 + IPI treated pts. We also did not observe any differences between pts who did or did not have lung, lymph node, or brain mets for either aPD1 or aPD1 + IPI. Interestingly, superior RR to aPD1 + IPI was observed in pts with bone mets compared to those without bone mets (91% vs. 58%, p = 0.048). Regarding number of sites, RR to aPD1 was greater in pts with ≤10 mets compared with those with > 10 (46% vs. 28%, p = 0.02), although no consistent relationship was observed at lower cutoffs. In multivariable analyses, diameter of largest tumor (tumor bulk) was independently associated with PFS (OR, 1.11, p < 0.001) and OS (OR 1.08, p < 0.001) whereas AJCC stage, lactate dehydrogenase, liver mets, ECOG performance status, number of mets, and prior therapies were not significant. Tumor bulk and other risk factors were not associated with PFS or OS in aPD1 + IPI. Conclusions: Tumor bulk was strongly and independently associated with clinical outcomes in aPD1 but not IPI + aPD1. Other associations with disease sites (liver and bone) need further validation. In conjunction with molecular biomarkers, clinical predictors may help guide selection of aPD1 or aPD1 + IPI.

scholarly journals In Vitro and In Vivo Stability a Cryptococcus neoformans Glucuronoxylomannan Epitope That Elicits Protective Antibodies

1999 ◽  
Vol 67 (6) ◽  
pp. 3096-3107 ◽  
Author(s):  
Wendy Cleare ◽  
Robert Cherniak ◽  
Arturo Casadevall
Keyword(s):  
Cryptococcus Neoformans ◽  
Parent Strain ◽  
Marked Reduction ◽  
Murine Models ◽  
Clear Trend ◽  
Agglutination Assay ◽  
Protective Antibodies ◽  
Selection Of

ABSTRACT The monoclonal antibody (MAb) 2H1 defines an epitope inCryptococcus neoformans capsular glucuronoxylomannan (GXM) that can elicit protective antibodies. In murine models of cryptococcosis, MAb 2H1 administration prolongs survival and reduces fungal burden but seldom clears the infection. The mechanism by whichC. neoformans persists and escape antibody-mediated clearance is not understood. One possibility is that variants that do not bind MAb 2H1 emerge in the course of infection. Using an agglutination-sedimentation protocol, we recovered a variant of strain 24067 that did not agglutinate, could not be serotyped, and had marked reduction in GXM O-acetyl groups. Binding of MAb 2H1 to 24067 variant cells produced a different immunofluorescence pattern and lower fluorescence intensity relative to the parent 24067 cells. Addition of MAb 2H1 to 24067 variant cells had no effect on cell charge. Phagocytic assays demonstrated that MAb 2H1 was not an effective opsonin for the 24067 variant. The 24067 variant was less virulent than the 24067 parent strain in mice, and MAb 2H1 administration did not prolong survival in animals infected with the variant strain. To investigate whether variants which do not bind MAb 2H1 are selected in experimental infection, three C. neoformans strains were serially passaged in mice given either MAb 2H1 or no antibody. Analysis of passaged isolates by agglutination assay, flow cytometry, and indirect immunofluorescence revealed changes in MAb 2H1 epitope expression but no clear trend with regards to gain or loss of MAb 2H1 epitope. C. neoformans variants with reduced MAb 2H1 epitope content can be isolated in vitro, but persistence of infection in mice given MAb 2H1 does not appear to be a result of selection of escape variants that lack the MAb 2H1 epitope.

scholarly journals The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humans

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Katia Koelle ◽  
David A Rasmussen
Keyword(s):  
Influenza Virus ◽  
Genetic Linkage ◽  
Influenza A ◽  
Deleterious Mutation ◽  
Rna Virus ◽  
Phylogenetic Analyses ◽  
Molecular Pathways ◽  
Deleterious Mutations ◽  
Mutation Load ◽  
Antigenic Evolution

Recent phylogenetic analyses indicate that RNA virus populations carry a significant deleterious mutation load. This mutation load has the potential to shape patterns of adaptive evolution via genetic linkage to beneficial mutations. Here, we examine the effect of deleterious mutations on patterns of influenza A subtype H3N2's antigenic evolution in humans. By first analyzing simple models of influenza that incorporate a mutation load, we show that deleterious mutations, as expected, act to slow the virus's rate of antigenic evolution, while making it more punctuated in nature. These models further predict three distinct molecular pathways by which antigenic cluster transitions occur, and we find phylogenetic patterns consistent with each of these pathways in influenza virus sequences. Simulations of a more complex phylodynamic model further indicate that antigenic mutations act in concert with deleterious mutations to reproduce influenza's spindly hemagglutinin phylogeny, co-circulation of antigenic variants, and high annual attack rates.

scholarly journals Effective Management of Gas Compressor Station Design Projects

1995 ◽  
Author(s):  
Anthony Cleveland ◽  
Edwin Humphries
Keyword(s):  
Team Work ◽  
Compressor Station ◽  
Effective Management ◽  
Successful Completion ◽  
Close Attention ◽  
Good Communication ◽  
Added Benefit ◽  
Design Projects ◽  
Effective Use ◽  
Selection Of

Downsizing and reduction in permanent engineering and design staff in gas transmission companies raises problems in coping with peak work loads, finding specialist expertise, and managing major projects. The solution being adopted by more and more organizations to deal with these issues is to call in a consultant. Consultants can provide the personnel and expertise to carry out this work with the added benefit that once completed there would be no in-house layoffs or redundancy expenses involved. Effective use of the consultant however, demands close attention to a number of things if waste of time and money is to be avoided. The paper considers the issues involved in the key selection of, and working with, a Consultant, and the key elements in the successful completion of the project. The importance of good communication and team work is stressed and the consequences of failure are discussed in case studies.

A Test of Evolutionary Theories of Senescence

2002 ◽  
Vol 2002 (37) ◽  
Author(s):  
Michael Rose ◽  
Brian Charlesworth
Keyword(s):  
Age Of Onset ◽  
Genetic Diseases ◽  
Mutation Accumulation ◽  
Deleterious Mutations ◽  
Fitness Components ◽  
Mean Values ◽  
Evolutionary Theories ◽  
Beneficial Effects ◽  
Effect Of Age ◽  
Selection Of

Senescence is the post-maturation decline in survivorship and fecundity that accompanies advancing age. Two main evolutionary theories have been proposed to account for senescence. (1) The mutation-accumulation theory. Deleterious mutations exerting their effects only late in life would tend to accumulate, because of their minimal effects on fitness. More precisely, exclusively late-acting deleterious mutations will attain higher equilibrium frequencies under mutation-selection balance than will mutations that act early, resulting in lower mean values for fitness components late in life (ref. 3 , p. 218). Medawar emphasized the possibility that this effect would be enhanced by selection of modifiers that postpone the age of onset of genetic diseases. (2) The pleiotropy theory. Williams suggested that many of the genes with beneficial effects on early fitness components have pleiotropy deleterious effects on late fitness components, but are nevertheless favoured by natural selection. (These theories are based on the decline with age in the effect of age-specific fitness-component changes on total fitness (ref. 3 , pp. 206-214 and refs 4, 5 ). Either or both of these theories could apply in any particular population.) Selection experiments in Drosophila and Tribolium support the pleiotropy theory, although one such experiment gave results that only bordered on significance, but the mutation-accumulation theory has never been tested. The present results provide evidence for the pleiotropy theory, but do not support the mutation-accumulation theory. Reproduced by permission. Michael Rose, Brian Charlesworth, A Test of Evolutionary Theories of Senescence. Nature 287 , 141-142 (1980).

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