Not Quite Lost in Translation: Mistranslation Alters Adaptive Landscape Topography and the Dynamics of Evolution

Mistranslation—the erroneous incorporation of amino acids into nascent proteins—is a source of protein variation that is orders of magnitude more frequent than DNA mutation. Like other sources of nongenetic variation, it can affect adaptive evolution. We study the evolutionary consequences of mistranslation with experimental data on mistranslation rates applied to three empirical adaptive landscapes. We find that mistranslation generally flattens adaptive landscapes by reducing the fitness of high fitness genotypes and increasing that of low fitness genotypes, but it does not affect all genotypes equally. Most importantly, it increases genetic variation available to selection by rendering many neutral DNA mutations nonneutral. Mistranslation also renders some beneficial mutations deleterious and vice versa. It increases the probability of fixation of 3–8% of beneficial mutations. Even though mistranslation increases the incidence of epistasis, it also allows populations evolving on a rugged landscape to evolve modestly higher fitness. Our observations show that mistranslation is an important source of nongenetic variation that can affect adaptive evolution on fitness landscapes in multiple ways

Meningioma involving the superior sagittal sinus: long-term outcome after robotic radiosurgery in primary and recurrent situation

ObjectiveTreatment for meningiomas involving the superior sagittal sinus (SSS) is challenging and proved to be associated with higher risks compared to other brain locations. Therapeutical strategies may be either microsurgical (sub-)total resection or adjuvant radiation, or a combination of both. Thrombosis or SSS occlusion following resection or radiosurgery needs to be further elucidated to assess whether single or combined treatment is superior. We here present tumor control and side effect data of robotic radiosurgery (RRS) in combination with or without microsurgery.MethodsFrom our prospective database, we identified 137 patients with WHO grade I meningioma involving the SSS consecutively treated between 2005 and 2020. Treatment decisions were interdisciplinary. Patients underwent RRS as initial/solitary treatment (group 1), as adjuvant treatment after subtotal resection (group 2), or due to recurrent tumor growth after preceding microsurgery (group 3). Positive tumor response was assessed by MRI and defined as reduction of more than 50% of volume. Study endpoints were time to recurrence (TTR), time to RRS, risk factors for decreased survival, and side effects. Overall and specific recurrence rates for treatment groups were analyzed. Side effect data included therapy-related morbidity during follow-up (FU).ResultsA total of 137 patients (median age, 58.3 years) with SSS meningiomas WHO grade I were analyzed: 51 patients (37.2%) in group 1, 15 patients (11.0%) in group 2, and 71 patients (51.8%) in group 3. Positive MR (morphological response) to therapy was achieved in 50 patients (36.4%), no response was observed in 25 patients (18.2%), and radiological tumor progression was detected in 8 patients (5.8%). Overall 5-year probability of tumor recurrence was 15.8% (median TTR, 41.6 months). Five-year probabilities of recurrence were 0%, 8.3.%, and 21.5% for groups 1–3 (p = 0.06). In multivariate analysis, tumor volume was significantly associated with extent of SSS occlusion (p = 0.026) and sex (p = 0.011). Tumor volume significantly correlated with TTR (p = 0.0046). Acute sinus venous thrombosis or venous congestion-associated bleedings did not occur in any of the groups.ConclusionRRS for grade I meningiomas with SSS involvement represents a good option as first-line treatment, occasionally also in recurrent and adjuvant scenarios as part of a multimodal treatment strategy

From RNA-seq to large-scale genotyping - genomics resources for rye (Secale cereale L.)

<p>Abstract</p> <p>Background</p> <p>The improvement of agricultural crops with regard to yield, resistance and environmental adaptation is a perpetual challenge for both breeding and research. Exploration of the genetic potential and implementation of genome-based breeding strategies for efficient rye (<it>Secale cereale </it>L.) cultivar improvement have been hampered by the lack of genome sequence information. To overcome this limitation we sequenced the transcriptomes of five winter rye inbred lines using Roche/454 GS FLX technology.</p> <p>Results</p> <p>More than 2.5 million reads were assembled into 115,400 contigs representing a comprehensive rye expressed sequence tag (EST) resource. From sequence comparisons 5,234 single nucleotide polymorphisms (SNPs) were identified to develop the Rye5K high-throughput SNP genotyping array. Performance of the Rye5K SNP array was investigated by genotyping 59 rye inbred lines including the five lines used for sequencing, and five barley, three wheat, and two triticale accessions. A balanced distribution of allele frequencies ranging from 0.1 to 0.9 was observed. Residual heterozygosity of the rye inbred lines varied from 4.0 to 20.4% with higher average heterozygosity in the pollen compared to the seed parent pool.</p> <p>Conclusions</p> <p>The established sequence and molecular marker resources will improve and promote genetic and genomic research as well as genome-based breeding in rye.</p

Gene expression noise can promote the fixation of beneficial mutations in fluctuating environments

Nongenetic phenotypic variation can either speed up or slow down adaptive evolution. We show that it can speed up evolution in environments in which available carbon and energy sources change over time. To this end, we use an experimentally validated model of Escherichia coli growth on two alternative carbon sources, glucose and acetate. On the superior carbon source (glucose), all cells achieve high growth rates, while on the inferior carbon source (acetate) only a small fraction of the population manages to initiate growth. Consequently, populations experience a bottleneck when the environment changes from the superior to the inferior carbon source. Growth on the inferior carbon source depends on a circuit under the control of a transcription factor that is repressed in the presence of the superior carbon source. We show that noise in the expression of this transcription factor can increase the probability that cells start growing on the inferior carbon source. In doing so, it can decrease the severity of the bottleneck and increase mean population fitness whenever this fitness is low. A modest amount of noise can also enhance the fitness effects of a beneficial allele. It can accelerate the spreading of such an allele, increase its likelihood of going to fixation, and reduce its fixation time. Central to the adaptation-enhancing principle we identify is the ability of noise to mitigate population bottlenecks. Because such bottlenecks are frequent in fluctuating environments, and because fluctuating environments themselves are ubiquitous, this principle may apply to a broad range of environments and organisms.Author summaryIndividuals that grow in the same environment and share the same genes may still differ in their behaviour and their traits. These differences between individuals arise from uncertainty inherent in all biological processes, and they are found in all domains of life. Although this random individual variability is itself short-lived, it still has the potential to shape evolution in the long term. For example, if a population encounters a harsh environment, random (nongenetic) differences between individuals can cause some individuals to cope better with the new environment than others. These rare individuals may give a population an advantage compared to populations with fewer such differences between individuals. Furthermore, if some of these rare individuals carry a beneficial gene variant, the beneficial effect of this gene variant may become amplified, and consequently spread faster in a population with more random variation. Using a realistic model of cell growth, we show that this mechanism not only works in unfavourable environments that are stable, but also in environments that switch back and forth between a favourable and an unfavourable state. Because many natural environments undergo such periodic changes, and because random differences between individuals are ubiquitous, the mechanism we have identified may be widespread in nature.</jats:sec

Gene expression noise can promote the fixation of beneficial mutations in fluctuating environments.

Nongenetic phenotypic variation can either speed up or slow down adaptive evolution. We show that it can speed up evolution in environments where available carbon and energy sources change over time. To this end, we use an experimentally validated model of Escherichia coli growth on two alternative carbon sources, glucose and acetate. On the superior carbon source (glucose), all cells achieve high growth rates, while on the inferior carbon source (acetate) only a small fraction of the population manages to initiate growth. Consequently, populations experience a bottleneck when the environment changes from the superior to the inferior carbon source. Growth on the inferior carbon source depends on a circuit under the control of a transcription factor that is repressed in the presence of the superior carbon source. We show that noise in the expression of this transcription factor can increase the probability that cells start growing on the inferior carbon source. In doing so, it can decrease the severity of the bottleneck and increase mean population fitness whenever this fitness is low. A modest amount of noise can also enhance the fitness effects of a beneficial allele that increases the fraction of a population initiating growth on acetate. Additionally, noise can protect this allele from extinction, accelerate its spread, and increase its likelihood of going to fixation. Central to the adaptation-enhancing principle we identify is the ability of noise to mitigate population bottlenecks, particularly in environments that fluctuate periodically. Because such bottlenecks are frequent in fluctuating environments, and because periodically fluctuating environments themselves are common, this principle may apply to a broad range of environments and organisms