Genetic suppression meets structure prediction: probing a spore germination receptor complex

Despite the thousands of spore germinant receptor operons identified in genomes of Bacilli and Clostridia, understanding how the three essential receptor components act as a signal transduction machine in germination remains limited. The paper by Amon et al in this issue uses the classical genetic approach of suppression to define a region of likely interaction between the GerAA and GerAB proteins: it provides a first glimpse into potential events within the receptor complex.

The Evolutionary Relevance of Social Learning and Transmission in Non-Social Arthropods with a Focus on Oviposition-Related Behaviors

Research on social learning has centered around vertebrates, but evidence is accumulating that small-brained, non-social arthropods also learn from others. Social learning can lead to social inheritance when socially acquired behaviors are transmitted to subsequent generations. Using oviposition site selection, a critical behavior for most arthropods, as an example, we first highlight the complementarities between social and classical genetic inheritance. We then discuss the relevance of studying social learning and transmission in non-social arthropods and document known cases in the literature, including examples of social learning from con- and hetero-specifics. We further highlight under which conditions social learning can be adaptive or not. We conclude that non-social arthropods and the study of oviposition behavior offer unparalleled opportunities to unravel the importance of social learning and inheritance for animal evolution.

The evolutionary relevance of social learning and transmission of behaviors in non-social arthropods

Research on social learning has centered around vertebrates, but evidence is accumulating that small-brained, non-social arthropods also learn from others. Social learning can lead to social inheritance when socially acquired behaviors are transmitted to subsequent generations. Here, we first highlight the complementarities between social and classical genetic inheritance, using oviposition site selection, a behavior critical for many non-social arthropods, as a hypothetical example. We then discuss the relevance of studying social learning and transmission in non-social arthropods and document known cases in the literature, including examples of social learning from con and hetero-specifics. We subsequently highlight under which conditions social learning can be adaptive or not. We conclude that non-social arthropods and the study of oviposition behavior offer unparalleled opportunities to increase our understanding of social learning and inheritance.

Engineering lithoheterotrophy in an obligate chemolithoautotrophic Fe(II) oxidizing bacterium

Neutrophilic Fe(II) oxidizing bacteria like Mariprofundus ferrooxydans are obligate chemolithoautotrophic bacteria that play an important role in the biogeochemical cycling of iron and other elements in multiple environments. These bacteria generally exhibit a singular metabolic mode of growth which prohibits comparative “omics” studies. Furthermore, these bacteria are considered non-amenable to classical genetic methods due to low cell densities, the inability to form colonies on solid medium, and production of copious amounts of insoluble iron oxyhydroxides as their metabolic byproduct. Consequently, the molecular and biochemical understanding of these bacteria remains speculative despite the availability of substantial genomic information. Here we develop the first genetic system in neutrophilic Fe(II) oxidizing bacterium and use it to engineer lithoheterotrophy in M. ferrooxydans, a metabolism that has been speculated but not experimentally validated. This synthetic biology approach could be extended to gain physiological understanding and domesticate other bacteria that grow using a single metabolic mode.

Determining When an Algebra Is an Evolution Algebra

Evolution algebras are non-associative algebras that describe non-Mendelian hereditary processes and have connections with many other areas. In this paper, we obtain necessary and sufficient conditions for a given algebra A to be an evolution algebra. We prove that the problem is equivalent to the so-called SDC problem, that is, the simultaneous diagonalisation via congruence of a given set of matrices. More precisely we show that an n-dimensional algebra A is an evolution algebra if and only if a certain set of n symmetric n×n matrices {M1,…,Mn} describing the product of A are SDC. We apply this characterisation to show that while certain classical genetic algebras (representing Mendelian and auto-tetraploid inheritance) are not themselves evolution algebras, arbitrarily small perturbations of these are evolution algebras. This is intringuing, as evolution algebras model asexual reproduction, unlike the classical ones.

An Efficient Solution to Travelling Salesman Problem using Genetic Algorithm with Modified Crossover Operator

The traveling salesman problem (TSP) is a famous NP-hard problem in the area of combinatorial optimization. It is utilized to locate the shortest possible route that visits every city precisely once and comes back to the beginning point from a given set of cities and distance. This paper proposes an efficient and effective solution for solving such a query. A modified crossover method using Minimal Weight Variable, Order Selection Crossover operator, a modified mutation using local optimization and a modified selection method using KMST is proposed. The crossover operator (MWVOSX) chooses a particular order from multiple orders which have the minimum cost and takes the remaining from the other parent in backward and forward order. Then it creates two new offspring. Further, it selects the least weight new offspring from those two offspring. The efficiency of the proposed algorithm is compared to the classical genetic algorithm. Comparisons show that our proposed algorithm provides much efficient results than the existing classical genetic algorithm.

Next Generation Sequencing-Based Mutational Profile of Therapy-Related AML and De Novo AML: Results from a Single Pediatric Institution in Argentina

Introduction Therapy-related acute myeloid leukemia (t-AML) and de novo AML (dnAML) are a group of aggressive diseases with poor outcome, in spite of recent advance in therapy. However, the alterations in different genes seems to be associated with this dismal prognosis. Recently, different groups have shown that t-AML in adult patients has a mutational profile distinct from dnAML. TP53 mutations were mostly described in t-AML. Next-generation sequencing (NGS) is a fast and accurate method used to demonstrate the presence of multiple alterations in several genes. The comparison of t-AML and dn-AML mutational profiles could be useful for improving our understanding of the molecular genetics events and in the outcome of each group as well. Objectives: 1-To describe the incidence of pathogenic variants in t-AML and dn-AML using a customized NGS panel, 2-to study correlations of these mutations with classical genetic features in each group of AMLs, 3-to compare the mutational profile of both diseases, and 4-to evaluate the prognostic impact of these mutations. Patients and Methods A total of 136 available DNA samples from non-APL dn-AML and 11 t-AML pediatric patients were retrospectively analyzed. The samples were sequenced on a Miseq (Illumina) platform, using a customized amplicon-based NGS panel (Illumina) including 65 genes. A total of 172,360 bp of DNA target regions were covered with 1,207 amplicons with a mean coverage of 1,308. Sequences obtained were analyzed by in-house bioinformatics pipeline, with particular analysis for NPM1, CEBPA and FLT3 genes, using Pindel and ITDseek algorithms. Results At least one pathogenic variant was detected in 100 out of 136 (74%) dn-AML analyzed cases, and 11 out of 11 (100%) t-AML patients. Overall, 317 mutations were found in 49 genes with a mean of 3.2 variants per patient for dn-AML, and 53 mutations in 26 genes with a mean of 4.8 variants per patient for t-AML. The most frequently mutated genes were: BCORL1 (5.4%, p=ns), FLT3 (5.0%, p=ns), KMT2A (5.0%, p=ns), BCOR (4.7%, p=0.0126), RB1 (4.4%, p=ns) for dn-AML, and KDM6A (15.1%, p<0.00001), BCOR (9.4%), CUX1 (9.4%, p=0.0020), BCORL1 (5.7%), FLT3 (5.7%) for t-AML. TP53 mutations were only detected in 5 dnAML cases. In the group of patients with dnAML, the distribution of classical genetic abnormalities was: KMT2A/11q23 (24%), RUNX1-RUNX1T1 (22%), Normal karyotype (19%), CBFB-MYH11 (9%). The most frequent mutations in normal karyotype were: FLT3 (38.1%, p=0.0019), CEBPA (27.3%, p=0.0001), NPM1 (28.6%, p<0.00001) and WT1 (23.8%, p=0.0001). In the group of t-AML, the genetic features were: KMT2A/11q23 (45%, p=ns) and Normal karyotype (9%, p=ns). CBFA2T2 mutation was statistically associated with the presence of RUNX1-RUNX1T1 in dn-AML (p=0.0002). No other significant association between variants and genetic groups was observed. Complete remission was achieved in 92% of cases in dn-AML and 72% in t-AML (median follow-up: 21 and 5 months respectively). Leukemia-free survival probability (LFSp) was 60(5)% [High-Risk: 55(6)%; Low-Risk: 71(10)%] for dn-AML and 13(11)% for t-AML (p=0.0008). In dn-AML group, LFSp(SE) of patients with at least one deleterious variant was 60(6)%, whereas those without any variant showed LFSp(SE): 58(10)(p=ns). In the normal karyotype group, the genotype NPM1/CEBPA-mutated plus FLT3/WT1-wild-type disclosed a LFSp(SE) of 86(13)% while remaining patients showed a LFSp(SE) of 42(14)% (p=ns). Conclusions We describe the incidence of mutations detected by NGS in a series of pediatric t-AML and dn-AML in our country. In spite of the limited number of patients, the mutation profile of t-AML seems to be different from the de novo counterpart. BCOR mutations were significantly associated with dn-AML cases, while KDM6A and CUX1 variants with t-AML patients. In contrast with adult reports, non TP53 mutations were observed in our group of t-AML patients. There was a significantly higher incidence of mutations in FLT3, CEBPA, NPM1 and WT1 within the normal karyotype group of dn-AML. The combined genotype NPM1/CEBPA-mutated plus FLT3/WT1-wild-type showed a trend to a better LFSp in dn-AML. The molecular genetic profile characterization of these heterogeneous diseases allows expansion of our understanding about the leukemogenic mechanisms involved. Disclosures No relevant conflicts of interest to declare.