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Evolution
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
Bollback and Huelsenbeck (2007) found that the clonal interference was alleviated by high mutation rates in large populations of the phage MS2. The phage MS2 was the most qualified subject for this investigation, since it demonstrated high mutation rate of 10−3 per nucleotide/replication (Drake 1993) and low recombination rate of 4.22 × 10−11 per nucleotide in multiply infected cells (Palasingam and Shaklee 1992). When a beneficial mutation was fixed in a population with very low recombination, the genetic background linked to that mutation was fixed. As a result, the beneficial mutations on different backgrounds experienced competition, or “clonal interference,” that could cause asexual populations to evolve more slowly than their sexual counterparts. Factors such as a large population size (N) and high mutation rates (μ) increased the number of competing beneficial mutations, and hence were expected to increase the intensity of clonal interference. However, the existing theory suggested that with very large values of Nμ, the severity of clonal interference might instead decline. The reason was that with large Nμ, the genomes, including both beneficial mutations, were rapidly created by recurrent mutation, obviating the need for recombination. Bollback and Huelsenbeck (2007) found that in the non-recombining MS2 populations with very large Nμ, the recurrent mutation did appear to ameliorate this cost of asexuality. In other words, this study selected populations of MS2 for growth at elevated temperatures and the frequency of a number of beneficial mutations was determined throughout the time course of the experiment (every ∼10 passages). These MS2 experimental data were used by the development of a new method for estimating effective population sizes, Ne, and selection coefficients, s (Bollback et al. 2008). In this study, the method was applied, after MS2, to estimate selection coefficients acting on the CCR5-Δ32 mutation on the basis of published samples of contemporary and ancient human DNA. Next, Bollback and Huelsenbeck (2009) turned to the parallel genetic evolution within and between the phage species of varying degrees of divergence when the three phage species, MS2, fr, and NL95, were adapted to a novel high-temperature environment. By adapting the three phage species to a novel environment, the authors found (i) a high rate of parallel genetic evolution at orthologous nucleotide and amino acid residues within species, (ii) parallel beneficial mutations did not occur in a common order in which they fix or appear in an evolving population, (iii) low rates of parallel evolution and convergent evolution between species, and (iv) the probability of parallel and convergent evolution between species was strongly effected by divergence. It is notable that the experimental MS2 adaptation data (Bollback and Huelsenbeck 2007) were used later in the population genetics by the elaboration of an alternative approximation to the mutant-frequency distribution that did not make any assumptions about the magnitude of selection or mutation and was much more computationally efficient than the standard diffusion approximation (Lacerda and Seoighe 2014).
Identifying prognostic gene panels in acute myeloid leukemia
Published in Expert Review of Hematology, 2023
Joaquin Sanchez-Garcia, Josefina Serrano, Esther Prados de La Torre, Juana Serrano-López, Clara Aparicio-Perez, E Barragán, Pau Montesinos
Core binding factor (CBF) AML (CBF-AML) is characterized by the presence of either t(8;21) (q22;q22) or inv(16) (p13q22)/t(16;16). These aberrations produce RUNX1::RUNX1T1 and CBFB::MYH11 fusion genes which generate abnormal CBF heterodimers with altered DNA binding provoking differentiation arrest and enhanced self-renewal capacity of leukemic cells [37]. CBF-AML encounter for 10–15% of AML and are considered of favorable prognosis due to the high remission rates with cytarabine/anthracycline-based chemotherapy induction (with or without Gentuzumab Ogamizin [GO]), and consolidation with high-dose cytarabine (HDAC)-based regimen, leading to 5 y OS up to 75% [38]. However, clonal interference defined as the presence of multiple mutations in KIT, NRAS, KRAS, FLT3, JAK2, and CBL genes are associated with inferior event-free-survival (EFS), although concurrent mutations in these genes do not modify risk categorization according to ELN2022 [39]. The presence of aberrant transcripts absent in normal hematopoiesis allows for quantitative RT-PCR monitoring of MRD in CBF AML. Data from multiple studies have confirmed the utility of MRD monitoring by standardized quantitative RT-PCR in identifying differences in outcomes [40].