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Molecular Analysis of Plant DNA Genomes: Conserved and Diverged DNA Sequences
Published in S. K. Dutta, DNA Systematics, 2019
The pioneering studies of the DNAs of most different organisms have led to three basic conclusions. First, the chemical composition and fundamental principles of genetic material organization of all living matter reveal a similar pattern; this is essential for correct genome comparisons. Second, the rate of divergent evolution of DNA varies in different branches of the phylogenetic tree; e.g., if nuclear DNA is compared, it is much higher among Angiospermae classes than among Mammalia (a taxon of the same rank and of the same evolutionary age as the classes of Angiospermae, monocots, and dicots). Third, it is now obvious that the objectively evaluated degree of DNA similarity between organisms can be used to measure their phylogenetic relatedness. This conclusion also applies to nucleotide gene sequences.
High Mobility Group Proteins: Purification, Properties, and Amino Acid Sequence Comparisons
Published in Isaac Bekhor, Carol J. Mirell, C. C. Liew, Progress in Nonhistone Protein Research, 1985
Gerald R. Reeck, David C. Teller
The similarities shown in Table 2 (some of which are among those pointed out by other investigators) occur in portions of the HMG proteins and the lysine-rich histones that appear to have similar functions, in a broad sense. The sequence similarities are between small portions of larger DNA-binding regions that are devoid of organized folding. These short stretches of sequence similarity could well reflect similarities in the details of DNA binding in those limited stretches of the polypetides. These DNA-binding regions in the HMG proteins and the lysine-rich histones are peculiar in amino acid composition (being rich in lysine, proline, and alanine). It is possible that this makeup is required for a randomly coiled DNA-binding polypeptide. Thus, the similarities between HMG-14 or -17 and the lysine-rich histones may have resulted from convergent evolution to compositional similarity. The similarity in composition would be expected to produce short stretches of sequence similarity. We have previously discussed this possibility in considering the N terminal regions of the core histones.52 Even if extensive stretches of sequence similarity were found in regions of distinctive and similar compositions (and this is not the case with the HMG proteins and lysine-rich histones), it would be difficult to argue convincingly that the sequence similarities resulted from divergent evolution.
Structure and Evolution of the Small Blue Proteins
Published in René Lontie, Copper Proteins and Copper Enzymes, 1984
The blue proteins have in common a copper(II) site with specific and unusual properties which suggests that the copper environment is similar in all of them. This situation — if true — can be the result of either convergent evolution, where similar requirements have promoted the evolution of the same structure from different origins (= analogy), or divergent evolution, where several or all of these proteins have evolved from a common ancestor ( = homology). If this latter possibility is valid, the evolutionary distances involved are tremendous: the common ancestor of say a pseudomonad bacterium and a higher plant inhabited our planet not later than some 3,000 million years ago. Nevertheless, molecular evolution aims at clarifying such relationships, many of which are inaccessible to traditional methods relying on morphology and the study of fossils.
High throughput and targeted screens for prepilin peptidase inhibitors do not identify common inhibitors of eukaryotic gamma-secretase
Published in Expert Opinion on Drug Discovery, 2023
Pradip Kumar Singh, Michael S. Donnenberg
According to the MEROPS database [35], PPP are members of the A24A family of aspartyl peptidases, characterized as polytopic transmembrane endopeptidases with aspartate residues in the active site. The active site aspartate residues are located at the cytosolic face of the membrane within conserved motifs: Xa-Xa-D-Xa-Xb-X-X-X-Xa-P and Xa-G-X-G-D-Xa-K-Xa-Xa-Xa (where Xa is hydrophobic, Xb is charged, D is aspartate, and X is any amino acid) [12,36]. Mutation of either aspartate led to enzyme inactivation [12]. Interestingly, polytopic membrane aspartyl proteases with a G-X-G-D motif are also found in the eukaryotic domain of life, including in humans. For example, presenilin-1 and presenilin-2 are part of the gamma (γ)-secretase protease complex, which cleaves the amyloid precursor protein into β-amyloid [37]. Along with signal peptide peptidase, they belong to the A22 family which shares the same clan AD with PPP A24 family in the MEROPS database. A missense mutation in presenilin-1 is associated with familial Alzheimer’s disease [38]. Presenilins have two conserved membrane-embedded aspartates at the active site and, as in PPP, both are required for endoproteolysis [39]. Although the G-X-G-D motif is found in both bacterial PPP and presenilins, in PPP the motif resides in the cytosol, whereas in eukaryotic enzymes it is embedded in the membrane [12,40]. Whether eukaryotic and bacterial polytopic membrane aspartyl proteases share these similarities as a result of convergent or divergent evolution remains an unresolved question [12,18,40–43].
The diagnostic challenges of patients with carcinoma of unknown primary
Published in Expert Review of Anticancer Therapy, 2020
The driver alteration in CUP seems to be chromosomal instability as it induces genomic instability and a mutator phenotype [17,18]. The subsequent proliferation of nonmalignant stem cells or non-stem cells at the primary site generates a population of stationary tumor cells that undergo a regression and/or dormancy process and motile cells leading to local tumor growth and metastatic dissemination [13,14]. The spread of migratory cells may occur before the local proliferation of non-motile neoplastic cells [16,19,20] or after a primary tumor has regressed at the primary site of cell transformation [21,22]. The motile cells disseminate according to two scenarios. The first, reported in 7.3–16% of cases, consists in acquiring mesenchymal features that facilitate motility, invasiveness and increased resistance to apoptosis [23–25]. The second, reported in 50% of cases, considers that tumor cells acquire a stem-cell phenotype that has the potential to disseminate [26]. After homing into multiple tissues, founder cells generate metastases that present a similarity in the mutational makeup of different CUP metastases which is consistent with the rapid clinical evolution. After extravasation into multiple issues, founder cells generate metastases leading patients to death rather quickly with only minimal divergent evolution [27].
Evolution and species-specific conservation of toll-like receptors in terrestrial vertebrates
Published in International Reviews of Immunology, 2018
Masoumeh Bagheri, Azadeh Zahmatkesh
Chicken TLR5 protein has a high degree of sequence similarity (about 50%) to human and murine TLR5, and all consist of N-terminal LRRs, a single TM domain, and an intracellular TIR domain. The predicted structures of the extracellular domain and TIR domain in chicken are also similar to their mammalian counterparts [64]. Chicken cells respond to bacterial flagellin with increased production of cytokines and chemokines [66,67]. TLR5 might be involved in flagellin-induced immunity in chicken [64], and it is expressed in a broad range of cell types [68,69] similar to its human ortholog [70]. It has also been reported that avian TLR5 as a bacterial-sensing TLR, has evolved under positive diversifying selection similar to mammals [50]. Reptile TLR5 has been shown to be phylogenetically most similar to TLR5 of birds. It has shown differential specificity compared with human TLR5 in flagellin recognition demonstrating their species-specific function during the divergent evolution of mammals and reptiles [71]. Although TLR5 is highly conserved in the reptilian lineage, the ligand-binding domain has been shaped by both episodic and positive selection. However, unlike ligand-binding domain, most of the mutations in TIR domain are synonymous substitutions which show the evolutionary constraints in TIR compared to ligand-binding domain within reptiles. Higher positive diversifying selection in TLR5 than viral TLRs was in concordance with similar studies on humans, rodents and birds [39].