Faculty Opinions recommendation of Reconstruction of ancestral metabolic enzymes reveals molecular mechanisms underlying evolutionary innovation through gene duplication.

The molecular mechanisms underlying the evolution of adaptive immunity-related proteins can be deduced by a thorough examination of the major histocompatibility complex (MHC). Currently, in vertebrates, there is a relatively large amount of research on MHCs in mammals and birds. However, research related to amphibian MHC genes and knowledge about the evolutionary patterns is limited. This study aimed to isolate the MHC class I genes from Chenfu’s Treefrog (Zhangixalus chenfui) and reveal the underlying evolutionary processes. A total of 23 alleles spanning the coding region of MHC class Ia genes were identified in 13 individual samples. Multiple approaches were used to test and identify recombination from the 23 alleles. Amphibian MHC class Ia alleles, from NCBI, were used to construct the phylogenetic relationships in MEGA. Additionally, the partition strategy was adopted to construct phylogenetic relationships using MrBayes and MEGA. The sites of positive selection were identified by FEL, PAML, and MEME. In Chenfu’s Treefrog, we found that: (1) recombination usually takes place between whole exons of MHC class Ia genes; (2) there are at least 3 loci for MHC class Ia, and (3) the diversity of genes in MHC class Ia can be attributed to recombination, gene duplication, and positive selection. We characterized the evolutionary mechanisms underlying MHC class Ia genes in Chenfu’s Treefrog, and in so doing, broadened the knowledge of amphibian MHC systems.

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Importance of adipocyte browning in the evolution of endothermy

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2019.0134 ◽

2020 ◽

Vol 375 (1793) ◽

pp. 20190134 ◽

Cited By ~ 5

Author(s):

Martin Jastroch ◽

Frank Seebacher

Keyword(s):

Adipose Tissue ◽

Heat Production ◽

Molecular Mechanisms ◽

Uncoupling Protein ◽

Muscular Activity ◽

Evolutionary Significance ◽

Potential Contribution ◽

Atp Production ◽

Evolutionary Innovation ◽

Brown Adipose

Endothermy changes the relationship between organisms and their environment fundamentally, and it is therefore of major ecological and evolutionary significance. Endothermy is characterized by non-shivering thermogenesis, that is metabolic heat production in the absence of muscular activity. In many eutherian mammals, brown adipose tissue (BAT) is an evolutionary innovation that facilitates non-shivering heat production in mitochondria by uncoupling food-derived substrate oxidation from chemical energy (ATP) production. Consequently, energy turnover is accelerated resulting in increased heat release. The defining characteristics of BAT are high contents of mitochondria and vascularization, and the presence of uncoupling protein 1. Recent insights, however, reveal that a range of stimuli such as exercise, diet and the immune system can cause the browning of white adipocytes, thereby increasing energy expenditure and heat production even in the absence of BAT. Here, we review the molecular mechanisms that cause browning of white adipose tissue, and their potential contribution to thermoregulation. The significance for palaeophysiology lies in the presence of adipose tissue and the mechanisms that cause its browning and uncoupling in all amniotes. Hence, adipocytes may have played a role in the evolution of endothermy beyond the more specific evolution of BAT in eutherians. This article is part of the theme issue ‘Vertebrate palaeophysiology’.

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Biochemical and Thermodynamic Analyses of Salmonella enterica Pat, a Multidomain, Multimeric Nε-Lysine Acetyltransferase Involved in Carbon and Energy Metabolism

mBio ◽

10.1128/mbio.00216-11 ◽

2011 ◽

Vol 2 (5) ◽

Cited By ~ 28

Author(s):

Sandy Thao ◽

Jorge C. Escalante-Semerena

Keyword(s):

Salmonella Enterica ◽

Metabolic Flux ◽

Molecular Mechanisms ◽

Gel Filtration ◽

Metabolic Enzymes ◽

Titration Calorimetry ◽

Lysine Acetylation ◽

Kinetic Behavior ◽

Carbon Utilization ◽

Content Type

ABSTRACT In the bacterium Salmonella enterica, the CobB sirtuin protein deacetylase and the Gcn5-related N ε-acetyltransferase (GNAT) Pat control carbon utilization and metabolic flux via N ε-lysine acetylation/deacetylation of metabolic enzymes. To date, the S. enterica Pat (SePat) acetyltransferase has not been biochemically characterized. Here we report the kinetic and thermodynamic characterization of the SePat enzyme using two of its substrates, acetyl coenzyme A (Ac-CoA) synthetase (Acs; AMP forming, EC 6.2.1.1) and Ac-CoA. The data showed typical Michaelis-Menten kinetic behavior when Ac-CoA was held at a saturating concentration while Acs was varied, and a sigmoidal kinetic behavior was observed when Acs was saturating and the Ac-CoA concentration was varied. The observation of sigmoidal kinetics and positive cooperativity for Ac-CoA is an unusual feature of GNATs. Results of isothermal titration calorimetry (ITC) experiments showed that binding of Ac-CoA to wild-type SePat produced a biphasic curve having thermodynamic properties consistent with two distinct sites. Biphasicity was not observed in ITC experiments that analyzed the binding of Ac-CoA to a C-terminal construct of SePat encompassing the predicted core acetyltransferase domain. Subsequent analytical gel filtration chromatography studies showed that in the presence of Ac-CoA, SePat oligomerized to a tetrameric form, whereas in the absence of Ac-CoA, SePat behaved as a monomer. The positive modulation of SePat activity by Ac-CoA, a product of the Acs enzyme that also serves as a substrate for SePat-dependent acetylation, is likely a layer of metabolic control. IMPORTANCE For decades, N ε-lysine acetylation has been a well-studied mode of regulation of diverse proteins involved in almost all aspects of eukaryotic physiology. Until recently, N ε-lysine acetylation was not considered a widespread phenomenon in bacteria. Recent studies have indicated that N ε-lysine acetylation and its impact on cellular metabolism may be just as diverse in bacteria as they are in eukaryotes. The S. enterica Pat enzyme, specifically, has recently been implicated in the modulation of many metabolic enzymes. Understanding the molecular mechanisms of how this enzyme controls the activity of diverse enzymes by N ε-lysine acetylation will advance our understanding of how the prokaryotic cell responds to its changing environment in order to meet its metabolic needs.

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Dual evolutionary origin of insect wings supported by an investigation of the abdominal wing serial homologs in Tribolium

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1711128115 ◽

2018 ◽

Vol 115 (4) ◽

pp. E658-E667 ◽

Cited By ~ 22

Author(s):

David M. Linz ◽

Yoshinori Tomoyasu

Keyword(s):

Molecular Mechanisms ◽

Genetic Regulation ◽

Evolutionary Origin ◽

Ancestral State ◽

Insect Wings ◽

Evolutionary Innovation ◽

Enhancer Trap Line ◽

Secondary Tissue ◽

Bona Fide ◽

Origin Hypothesis

The origin of insect wings is still a highly debated mystery in biology, despite the importance of this evolutionary innovation. There are currently two prominent, but contrasting wing origin hypotheses (the tergal origin hypothesis and the pleural origin hypothesis). Through studies in the Tribolium beetle, we have previously obtained functional evidence supporting a third hypothesis, the dual origin hypothesis. Although this hypothesis can potentially unify the two competing hypotheses, it requires further testing from various fields. Here, we investigated the genetic regulation of the tissues serially homologous to wings in the abdomen, outside of the appendage-bearing segments, in Tribolium. We found that the formation of ectopic wings in the abdomen upon homeotic transformation relies not only on the previously identified abdominal wing serial homolog (gin-trap), but also on a secondary tissue in the pleural location. Using an enhancer trap line of nubbin (a wing lineage marker), we were able to visualize both of these two tissues (of tergal and pleural nature) contributing to form a complete wing. These results support the idea that the presence of two distinct sets of wing serial homologs per segment represents an ancestral state of the wing serial homologs, and can therefore further support a dual evolutionary origin of insect wings. Our analyses also uncovered detailed Hox regulation of abdominal wing serial homologs, which can be used as a foundation to elucidate the molecular mechanisms that have facilitated the evolution of bona fide insect wings, as well as the diversification of other wing serial homologs.

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Genomic signatures of globally enhanced gene duplicate accumulation in the megadiverse higher Diptera fueling intralocus sexual conflict resolution

PeerJ ◽

10.7717/peerj.10012 ◽

2020 ◽

Vol 8 ◽

pp. e10012

Author(s):

Riyue Bao ◽

Markus Friedrich

Keyword(s):

Conflict Resolution ◽

Gene Duplication ◽

Sexual Conflict ◽

Sequence Divergence ◽

Gene Families ◽

Specific Gene ◽

Background Rate ◽

Intralocus Sexual Conflict ◽

Evolutionary Innovation ◽

Gene Duplicate

Gene duplication is an important source of evolutionary innovation. To explore the relative impact of gene duplication during the diversification of major insect model system lineages, we performed a comparative analysis of lineage-specific gene duplications in the fruit fly Drosophila melanogaster (Diptera: Brachycera), the mosquito Anopheles gambiae (Diptera: Culicomorpha), the red flour beetle Tribolium castaneum (Coleoptera), and the honeybee Apis mellifera (Hymenoptera). Focusing on close to 6,000 insect core gene families containing maximally six paralogs, we detected a conspicuously higher number of lineage-specific duplications in Drosophila (689) compared to Anopheles (315), Tribolium (386), and Apis (223). Based on analyses of sequence divergence, phylogenetic distribution, and gene ontology information, we present evidence that an increased background rate of gene duplicate accumulation played an exceptional role during the diversification of the higher Diptera (Brachycera), in part by providing enriched opportunities for intralocus sexual conflict resolution, which may have boosted speciation rates during the early radiation of the megadiverse brachyceran subclade Schizophora.

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Ancient Coretention of Paralogs of Cid Centromeric Histones and Cal1 Chaperones in Mosquito Species

Molecular Biology and Evolution ◽

10.1093/molbev/msaa056 ◽

2020 ◽

Vol 37 (7) ◽

pp. 1949-1963 ◽

Cited By ~ 2

Author(s):

Lisa E Kursel ◽

Frances C Welsh ◽

Harmit S Malik

Keyword(s):

Gene Duplication ◽

Mosquito Species ◽

Expression Patterns ◽

Specific Expression ◽

Animal Evolution ◽

Protein Motifs ◽

Anopheles Mosquitoes ◽

Evolutionary Innovation ◽

Intralocus Conflict ◽

Centromeric Proteins

Abstract Despite their essential role in chromosome segregation in most eukaryotes, centromeric histones (CenH3s) evolve rapidly and are subject to gene turnover. We previously identified four instances of gene duplication and specialization of Cid, which encodes for the CenH3 in Drosophila. We hypothesized that retention of specialized Cid paralogs could be selectively advantageous to resolve the intralocus conflict that occurs on essential genes like Cid, which are subject to divergent selective pressures to perform multiple functions. We proposed that intralocus conflict could be a widespread phenomenon that drives evolutionary innovation in centromeric proteins. If this were the case, we might expect to find other instances of coretention and specialization of centromeric proteins during animal evolution. Consistent with this hypothesis, we find that most mosquito species encode two CenH3 (mosqCid) genes, mosqCid1 and mosqCid2, which have been coretained for over 150 My. In addition, Aedes species encode a third mosqCid3 gene, which arose from an independent gene duplication of mosqCid1. Like Drosophila Cid paralogs, mosqCid paralogs evolve under different selective constraints and show tissue-specific expression patterns. Analysis of mosqCid N-terminal protein motifs further supports the model that mosqCid paralogs have functionally diverged. Extending our survey to other centromeric proteins, we find that all Anopheles mosquitoes encode two CAL1 paralogs, which are the chaperones that deposit CenH3 proteins at centromeres in Diptera, but a single CENP-C paralog. The ancient coretention of paralogs of centromeric proteins adds further support to the hypothesis that intralocus conflict can drive their coretention and functional specialization.

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Interplay between Epigenetics and Cellular Metabolism in Colorectal Cancer

Biomolecules ◽

10.3390/biom11101406 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1406

Author(s):

Xiaolin Zhang ◽

Zhen Dong ◽

Hongjuan Cui

Keyword(s):

Signaling Pathways ◽

Molecular Mechanisms ◽

Tumor Development ◽

Cellular Metabolism ◽

Metabolic Enzymes ◽

Oncogenic Signaling ◽

Genes Encoding ◽

Potential Applications ◽

The One ◽

Epigenetic Processes

Cellular metabolism alterations have been recognized as one of the most predominant hallmarks of colorectal cancers (CRCs). It is precisely regulated by many oncogenic signaling pathways in all kinds of regulatory levels, including transcriptional, post-transcriptional, translational and post-translational levels. Among these regulatory factors, epigenetics play an essential role in the modulation of cellular metabolism. On the one hand, epigenetics can regulate cellular metabolism via directly controlling the transcription of genes encoding metabolic enzymes of transporters. On the other hand, epigenetics can regulate major transcriptional factors and signaling pathways that control the transcription of genes encoding metabolic enzymes or transporters, or affecting the translation, activation, stabilization, or translocation of metabolic enzymes or transporters. Interestingly, epigenetics can also be controlled by cellular metabolism. Metabolites not only directly influence epigenetic processes, but also affect the activity of epigenetic enzymes. Actually, both cellular metabolism pathways and epigenetic processes are controlled by enzymes. They are highly intertwined and are essential for oncogenesis and tumor development of CRCs. Therefore, they are potential therapeutic targets for the treatment of CRCs. In recent years, both epigenetic and metabolism inhibitors are studied for clinical use to treat CRCs. In this review, we depict the interplay between epigenetics and cellular metabolism in CRCs and summarize the underlying molecular mechanisms and their potential applications for clinical therapy.

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In Scarcity and Abundance: Metabolic Signals Regulating Cell Growth

Physiology ◽

10.1152/physiol.00005.2013 ◽

2013 ◽

Vol 28 (5) ◽

pp. 298-309 ◽

Cited By ~ 6

Author(s):

Shady Saad ◽

Matthias Peter ◽

Reinhard Dechant

Keyword(s):

Cell Growth ◽

Metabolic Activity ◽

Nutrient Availability ◽

Molecular Mechanisms ◽

Metabolic Enzymes ◽

Nutrient Supply ◽

Nutrient Sensing ◽

Recent Advances ◽

Growth Promoting

Although nutrient availability is a major driver of cell growth, and continuous adaptation to nutrient supply is critical for the development and survival of all organisms, the molecular mechanisms of nutrient sensing are only beginning to emerge. Here, we highlight recent advances in the field of nutrient sensing and discuss arising principles governing how metabolism might regulate growth-promoting pathways. In addition, we discuss signaling functions of metabolic enzymes not directly related to their metabolic activity.

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The role of metabolic enzymes in mesenchymal tumors and tumor syndromes: genetics, pathology, and molecular mechanisms

Laboratory Investigation ◽

10.1038/s41374-017-0003-6 ◽

2018 ◽

Vol 98 (4) ◽

pp. 414-426 ◽

Cited By ~ 8

Author(s):

Inga-Marie Schaefer ◽

Jason L. Hornick ◽

Judith V. M. G. Bovée

Keyword(s):

Molecular Mechanisms ◽

Metabolic Enzymes ◽

Mesenchymal Tumors

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