Journal of Molecular Evolution最新文献

Hemoglobin and red blood cells (erythrocytes) have been studied extensively from the perspective of life and biomedical sciences. However, no analysis of hemoglobin and red blood cells from the perspective of chemical thermodynamics has been reported in the literature. Such an analysis would provide an insight into their structure and turnover from the aspect of biothermodynamics and bioenergetics. In this paper, a biothermodynamic analysis was made of hemoglobin and red blood cells. Molecular formulas, empirical formulas, biosynthesis reactions, and thermodynamic properties of formation and biosynthesis were determined for the alpha chain, beta chain, heme B, hemoglobin and red blood cells. Empirical formulas and thermodynamic properties of hemoglobin were compared to those of other biological macromolecules, which include proteins and nucleic acids. Moreover, the energetic requirements of biosynthesis of hemoglobin and red blood cells were analyzed. Based on this, a discussion was made of the specific structure of red blood cells (i.e. no nuclei nor organelles) and its role as an evolutionary adaptation for more energetically efficient biosynthesis needed for the turnover of red blood cells.

The highly dynamic nature of the Cotton leaf curl virus (CLCuV) complex (causing Cotton leaf curl disease, a significant global threat to cotton) presents a formidable challenge in unraveling precise molecular mechanisms governing viral-host interactions. To address this challenge, the present study investigated the molecular interactions of 6 viral proteins (Rep, TrAP, C4, C5, V2, and βC1) with 18 cotton Transcriptional Gene Silencing (TGS) proteins. Protein-protein dockings conducted for different viral-host protein pairs using Clustered Protein Docking (ClusPro) and Global RAnge Molecular Matching (GRAMM) (216 docking runs), revealed variable binding energies. The interacting pairs with the highest binding affinities were further scrutinized using bioCOmplexes COntact MAPS (COCOMAPS) server, which revealed robust binding of three viral proteins- TrAP, C4, and C5 with 14 TGS proteins, identifying several novel interactions (not reported yet by earlier studies), such as TrAP targeting DCL3, HDA6, and SUVH6; C4 targeting RAV2, CMT2, and DMT1; and C5 targeting CLSY1, RDR1, RDR2, AGO4, SAMS, and SAHH. Visualizing these interactions in PyMol provided a detailed insight into interacting regions. Further assessment of the impact of 18 variants of the C4 protein on interaction with CMT2 revealed no correlation between sequence variation and docking energies. However, conserved residues in the C4 binding regions emerged as potential targets for disrupting viral integrity. Hence, this study provides valuable insights into the viral-host interplay, advancing our understanding of Cotton leaf curl Multan virus pathogenicity and opening novel avenues for devising various antiviral strategies by targeting the host-viral interacting regions after experimental validation.

Microscopic evolution at the functional biomolecular level is an ongoing process. Leveraging functional and high-throughput assays, along with computational data mining, has led to a remarkable expansion of our understanding of multifunctional protein (and gene) families over the past few decades. Various molecular and intermolecular mechanisms are now known that collectively meet the cumulative multifunctional demands in higher organisms along an evolutionary path. This multitasking ability is attributed to a certain degree of intrinsic or adapted flexibility at the structure-function level. Evolutionary diversification of structure-function relationships in proteins highlights the functional importance of intrinsically disordered proteins/regions (IDPs/IDRs) which are highly dynamic biological soft matter. Multifunctionality is favorably supported by the fluid-like shapes of IDPs/IDRs, enabling them to undergo disorder-to-order transitions upon binding to different molecular partners. Other new malleable members of the protein superfamily, such as those involved in fold-switching, also undergo structural transitions. This new insight diverges from all traditional notions of functional singularity in enzyme classes and emphasizes a far more complex, multi-layered diversification of protein functionality. However, a thorough review in this line, focusing on flexibility and function-driven structural transitions related to evolved multifunctionality in proteins, is currently missing. This review attempts to address this gap while broadening the scope of multifunctionality beyond single protein sequences. It argues that protein intrinsic disorder is likely the most striking mechanism for expressing multifunctionality in proteins. A phenomenological analogy has also been drawn to illustrate the increasingly complex nature of modern digital life, driven by the need for multitasking, particularly involving media.

In this report, we propose a novel mathematical model of the origin and evolution of sex determination in vertebrates that is based on the stochastic epigenetic modification (SEM) mechanism. We have previously shown that SEM, with rates consistent with experimental observation, can both increase the rate of gene fixation and decrease pseudogenization, thus dramatically improving the efficacy of evolution. Here, we present a conjectural model of the origin and evolution of sex determination wherein the SEM mechanism alone is sufficient to parsimoniously trigger and guide the evolution of heteromorphic sex chromosomes from the initial homomorphic chromosome configuration, without presupposing any allele frequency differences. Under this theoretical model, the SEM mechanism (i) predated vertebrate sex determination origins and evolution, (ii) has been conveniently and parsimoniously co-opted by the vertebrate sex determination systems during the evolutionary transitioning to the extant vertebrate sex determination, likely acting "on top" of these systems, and (iii) continues existing, alongside all known vertebrate sex determination systems, as a universal pan-vertebrate sex determination modulation mechanism.

Major evolutionary transitions, such as the shift of cetaceans from terrestrial to marine life, can put pressure on sensory systems to adapt to a new set of relevant stimuli. Relatively little is known about the role of smell in the evolution of mysticetes (baleen whales). While their toothed cousins, the odontocetes, lack the anatomical features to smell, it is less clear whether baleen whales have retained this sense, and if so, when the pressure on olfaction diverged in the cetacean evolutionary lineage. We examined eight genes encoding olfactory signal transduction pathway components and key chaperones for signs of inactivating mutations and selective pressures. All of the genes we examined were intact in all eight mysticete genomes examined, despite inactivating mutations in odontocete homologs in multiple genes. We also tested several models representing various hypotheses regarding the evolutionary history of olfaction in cetaceans. Our results support a model where olfactory ability is specifically reduced in the odontocete lineage following their split from stem cetaceans and serve to clarify the evolutionary history of olfaction in cetaceans.

Most cancers present with mutations or amplifications in distinctive tumor promoter genes that activate principal cell-signaling cascades promoting cell proliferation, dedifferentiation, cell survival, and replicative immortality. Somatic mutations found in this these driver proto-oncogenes invariably result in constitutive activation of the encoded protein. A salient feature of the activating mutations observed throughout many thousands of clinical tumor specimens reveals these driver missense mutations are recurrent and restricted to just one or very few codons of the entire gene, suggesting they have been positively selected during the course of tumor development. The purpose of this study is to investigate whether these characteristic oncogenic driver mutations are observed in the germline genes of any metazoan species. Six well-known tumor promoter genes were chosen for this survey including BRAF, KRAS, JAK2, PIK3CA, EGFR, and IDH1/2. The sites of all driver mutations were found to occur in highly conserved regions of each gene comparing protein sequences throughout diverse phyla of metazoan species. None of the oncogenic missense mutations were found in germlines of any species of current genome and protein databases. Despite many tumors readily selecting these somatic mutations, the conclusion drawn from this study is that these variants are negatively rejected if encountered as a germline mutation. While cancer expansion ensues from dysregulated growth elicited by these mutations, this effect is likely detrimental to embryonic development and/or survival of multicellular organisms. Although all oncogenic mutations considered here are gain-of-function where five of the six increase activity of the encoded proteins, clonal advancement promotes tumor growth by these genomic changes without conferring selection advantages benefiting the organism or species.

Biogenic volatile organic compounds (VOCs) constitute a significant portion of gas-phase metabolites in modern ecosystems and have unique roles in moderating atmospheric oxidative capacity, solar radiation balance, and aerosol formation. It has been theorized that VOCs may account for observed geological and evolutionary phenomena during the Archaean, but the direct contribution of biology to early non-methane VOC cycling remains unexplored. Here, we provide an assessment of all potential VOCs metabolized by the last universal common ancestor (LUCA). We identify enzyme functions linked to LUCA orthologous protein groups across eight literature sources and estimate the volatility of all associated substrates to identify ancient volatile metabolites. We hone in on volatile metabolites with confirmed modern emissions that exist in conserved metabolic pathways and produce a curated list of the most likely LUCA VOCs. We introduce volatile organic metabolites associated with early life and discuss their potential influence on early carbon cycling and atmospheric chemistry.

The existence of LUCA in the distant past is the logical consequence of the binary mechanism of cell division. The biosphere in which LUCA and contemporaries were living was the product of a long cellular evolution from the origin of life to the second age of the RNA world. A parsimonious scenario suggests that the molecular fabric of LUCA was much simpler than those of modern organisms, explaining why the evolutionary tempo was faster at the time of LUCA than it was during the diversification of the three domains. Although LUCA was possibly equipped with a RNA genome and most likely lacked an ATP synthase, it was already able to perform basic metabolic functions and to produce efficient proteins. However, the proteome of LUCA and its inferred metabolism remains to be correctly explored by in-depth phylogenomic analyses and updated datasets. LUCA was probably a mesophile or a moderate thermophile since phylogenetic analyses indicate that it lacked reverse gyrase, an enzyme systematically present in all hyperthermophiles. The debate about the position of Eukarya in the tree of life, either sister group to Archaea or descendants of Archaea, has important implications to draw the portrait of LUCA. In the second alternative, one can a priori exclude the presence of specific eukaryotic features in LUCA. In contrast, if Archaea and Eukarya are sister group, some eukaryotic features, such as the spliceosome, might have been present in LUCA and later lost in Archaea and Bacteria. The nature of the LUCA virome is another matter of debate. I suggest here that DNA viruses only originated during the diversification of the three domains from an RNA-based LUCA to explain the odd distribution pattern of DNA viruses in the tree of life.