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Bayesian Inference: Biological Processes that Follow a Continuous Time Markov Chain
Published in Lyle D. Broemeling, Bayesian Analysis of Infectious Diseases, 2021
It is left for the student to develop a formal Bayesian test of α = β. For the Bayesian method of testing hypotheses, see Lee [5, p. 126–127]. Also, as in the previous example of molecular evolution (the Jukes-Cantor model), it is easy to derive the predictive density of a future adenine (or thymine) holding time, and this will be left as an exercise for the student.
Evolution
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
In parallel, the adaptive response of the phage MS2 to a novel environment was studied by Betancourt (2009). Thus, the three MS2 lines were adapted to rapid growth and lysis at cold temperature for a minimum of 50 phage generations and subjected to whole-genome sequencing. The adaptive substitutions were identified, the changes in frequency of adaptive mutations through the course of the experiment were monitored, and the effect on phage growth rate of each substitution was measured. All three lines showed a substantial increase in fitness, namely, a two- to threefold increase in growth rate, due to a modest number of substitutions, three to four. The data showed some evidence that the substitutions occurring early in the experiment had larger beneficial effects than later ones, in accordance with the expected diminishing returned relationship between the fitness effects of a mutation and its order of substitution. The patterns of the molecular evolution suggested an abundant supply of the beneficial mutations in this system. Nevertheless, some beneficial mutations appeared to have been lost, possibly due to accumulation of the beneficial mutations on other genetic backgrounds, clonal interference, and negatively epistatic interactions with other beneficial mutations (Betancourt 2009).
23S rRNA-Derived Small Ribosomal RNAs: Their Structure and Evolution with References to Plant Phylogeny
Published in S. K. Dutta, DNA Systematics, 2019
The constant rate of macromolecule evolution is determined by the invariability of its functions. If functions alter, the change in the set of tolerable and advantageous mutational states of the gene takes place, with a resultant increase in the rate of mutational replacement. This inconstancy of molecular evolution rate hampers the inference of phylogeny from sequence data. Such phyletic lines, with the evolution rate deviating from the average, may be revealed upon studying the peculiarities of the 5.8S rRNA secondary structure, and also upon comparing the phylogenetic trees built by different procedures and for different macromolecules. On the other hand, the “comparative-morphological” analysis of rRNA may prove quite useful in molecular-evolutionary studies. As Goodman155 states, despite the perfection of the methods for phylogenetic reconstruction from sequence data there are cases of inconsistency between trees and strongly supported traditional views on the species phylogeny. In these cases, additional valuable information may be provided by the study of such qualitative molecular characters as the presence of certain deletions or insertions and the spatial structure peculiarities.
Selection of target-binding proteins from the information of weakly enriched phage display libraries by deep sequencing and machine learning
Published in mAbs, 2023
Tomoyuki Ito, Thuy Duong Nguyen, Yutaka Saito, Yoichi Kurumida, Hikaru Nakazawa, Sakiya Kawada, Hafumi Nishi, Koji Tsuda, Tomoshi Kameda, Mitsuo Umetsu
Recently, machine learning has been combined with directed molecular evolution.9–19 For improving or changing the function of protein interested, the sequences and functions of the variants in the initial mutagenesis library were evaluated and used as training data to construct a machine learning model that predicts the function from the sequence. By using the model, a second-round library that contains predicted variants to have improved or changed functions is generated. This method has successfully enabled us to design a library with high enrichment of desirable variants in the directed evolution of various proteins, including fluorescent proteins,11–13 enzymes,8,14–17 and others.18,19 In the field of antibody engineering, deep sequencing data has been used as training data of machine learning. Deep sequencing analysis of the surface-display system supplies a large number of sequences with their antigen-binding properties, and then, a machine learning model trained with the deep sequencing data has proposed sequences with higher target affinity than that of the experimentally selected variants.20–24
Ex vivo gene therapy for lysosomal storage disorders: future perspectives
Published in Expert Opinion on Biological Therapy, 2023
Edina Poletto, Andrew Oliveira Silva, Ricardo Weinlich, Priscila Keiko Matsumoto Martin, Davi Coe Torres, Roberto Giugliani, Guilherme Baldo
While CRISPR-Cas technology has revolutionized gene therapy approaches, some safety concerns have been raised. Cas-gRNA complexes can eventually bind and cleave unspecific DNA sequences throughout the genome that are similar to their on-target sites; such events are known as off-targets. To overcome this issue, several Cas orthologs have been further characterized and found to be naturally high-fidelity nucleases, like Cas9 from Neisseria meningitides (Nme2Cas9) and Cas12a from Acidaminococcus sp. and Lachnospiraceae bacterium (AsCas12a and LbCas12a, respectively) [25,26]. Moreover, there is a great interest in the development of new Cas variants with high-fidelity features through directed molecular evolution or structure-guided protein engineering [27]. For example, HiFi Cas9 (R691A) has been shown to possess reduced off-target activity, while being capable of sustaining similar on-target levels as the wild-type SpCas9 [28]. More recently, it has been demonstrated that DSBs caused by the CRISPR-Cas system can affect genome integrity, leading to aneuploidy [23], chromosome rearrangements [29], chromothripsis [30], and p53 activation [31]. Therefore, there is a huge demand for the development of more secure and less error-prone gene editing tools for therapeutic purposes.
Identification, characterization, and molecular phylogeny of scorpion enolase (Androctonus crassicauda and Hemiscorpius lepturus)
Published in Toxin Reviews, 2023
Elham Pondehnezhadan, Atefeh Chamani, Fatemeh Salabi, Reihaneh Soleimani
The evolutionary origin and relevance of scorpions have been the subject of many studies in recent decades, especially recent pan-genome studies that support the Arachnopulmonata hypothesis: a sister-group relationship between scorpions and tetrapulmonates (i.e. spiders and allied orders) (Regier et al. 2010, Sharma et al. 2014, 2015). Previous morphological-based phylogenetic approaches are restricted to those scorpions exemplifying morphological stasis (Prendini and Wheeler 2005, Prendini et al. 2006). To address this challenge, however, phylogenetic relationships can be inferred more precisely using both molecular and morphological methods (Chippaux and Goyffon 2008). Molecular phylogeny compares homologous DNA or protein sequences to decide the relationships among organisms or genes. It constructs a hierarchical phylogenetic tree based on the genetic divergences of the similarity or dissimilarity of homologous molecules from different organisms, resulting from molecular evolution over time (Patwardhan et al. 2014).