Highlights • I examine the origins of resistance of organisms to mutations. • Robustness to mutations is a universal property of biological systems. • Experimental evolution of microbes reveals the ...origin of robustness. • Genetic redundancy through gene duplication gives rise to mutational robustness.
Gene duplicates are a major source of evolutionary novelties in the form of new or specialized functions and play a key role in speciation. Gene duplicates are generated through whole genome ...duplications (WGD) or small-scale genome duplications (SSD). Although WGD preserves the stoichiometric relationships between duplicates, those arising from SSD are usually unbalanced and are expected to follow different evolutionary dynamics than those formed by WGD. To dissect the role of the mechanism of duplication in these differential dynamics and determine whether this role was shared across species, we performed a genome wide evolutionary analysis of gene duplications arising from the most recent WGD events and contemporary episodes of SSD in four model species representing distinct plant evolutionary lineages. We found an excess of relaxed purifying selection after duplication in SSD paralogs compared with WGD, most of which may have been the result of functional divergence events between gene copies as estimated by measures of genetic distances. These differences were significant in three angiosperm genomes but not in the moss species Physcomitrella patens. Although the comparison of models of evolution does not attribute a relevant role to the mechanism of duplication in the evolution duplicates, distribution of retained genes among Gene Ontology functional categories support the conclusion that evolution of gene duplicates depends on its origin of duplication (WGD and SSD) but, most importantly, on the species. Similar lineage-specific biases were also observed in protein network connectivity, translational efficiency, and selective constraints acting on synonymous codon usage. Although the mechanism of duplication may determine gene retention, our results attribute a dominant role to the species in determining the ultimate pattern of duplicate gene retention and reveal an unanticipated complexity in the evolutionary dynamics and functional specialization of duplicated genes in plants.
The cell central metabolism has been shaped throughout evolutionary times when facing challenges from the availability of resources. In the budding yeast,
, a set of duplicated genes originating from ...an ancestral whole-genome and several coetaneous small-scale duplication events drive energy transfer through glucose metabolism as the main carbon source either by fermentation or respiration. These duplicates (~a third of the genome) have been dated back to approximately 100 MY, allowing for enough evolutionary time to diverge in both sequence and function. Gene duplication has been proposed as a molecular mechanism of biological innovation, maintaining balance between mutational robustness and evolvability of the system. However, some questions concerning the molecular mechanisms behind duplicated genes transcriptional plasticity and functional divergence remain unresolved. In this work we challenged
to the use of lactic acid/lactate as the sole carbon source and performed a small adaptive laboratory evolution to this non-fermentative carbon source, determining phenotypic and transcriptomic changes. We observed growth adaptation to acidic stress, by reduction of growth rate and increase in biomass production, while the transcriptomic response was mainly driven by repression of the whole-genome duplicates, those implied in glycolysis and overexpression of ROS response. The contribution of several duplicated pairs to this carbon source switch and acidic stress is also discussed.
ABSTRACT
Chaperonin 60 is the prototypic molecular chaperone, an essential protein in eukaryotes and prokaryotes, whose sequence conservation provides an excellent basis for phylogenetic analysis. ...Escherichia coli chaperonin 60 (GroEL), the prototype of this family of proteins, has an established oligomeric‐structure‐based folding mechanism and a defined population of folding partners. However, there is a growing number of examples of chaperonin 60 proteins whose crystal structures and oligomeric composition are at variance with GroEL, suggesting that additional complexities in the protein‐folding function of this protein should be expected. In addition, many organisms have multiple chaperonin 60 proteins, some of which have lost their protein‐folding ability. It is emerging that this highly conserved protein has evolved a bewildering variety of additional biological functions – known as moonlighting functions – both within the cell and in the extracellular milieu. Indeed, in some organisms, it is these moonlighting functions that have been left after the loss of the protein‐folding activity. This highlights the major paradox in the biology of chaperonin 60. This article reviews the relationship between the folding and non‐folding (moonlighting) activities of the chaperonin 60 family and discusses current knowledge on their molecular evolution focusing on protein domains involved in the non‐folding chaperonin functions in an attempt to understand the emerging biology of this evolutionarily ancient protein family.
Moonlighting proteins exhibit functions that are alternative to their main role in the cell. Heat-shock proteins, also known as molecular chaperones, are now recognized for their wide range of ...activities in and/or outside the cell, being prominent examples of moonlighting proteins. Chaperonins are highly conserved molecular chaperones that fold other proteins into their native conformation allowing them to carry out essential functions in the cell. Activities alternative to folding have been reported for the chaperonin (Cpn) 60 protein. Preservation of various alternative functions in one protein conflicts with the optimization of each of the functions. What evolutionary mechanisms have allowed the persistence of moonlighting proteins, and in particular the chaperonins, remains a mystery. In the present article, I argue that mechanisms that increase the resistance of phenotypes to genetic and environmental perturbations enable the persistence of a reservoir of genetic variants, each potentially codifying for a distinct function. Gene duplication is one such mechanism that has characterized the expansion and has been concomitant with the emergence of novel functions in these protein families. Indeed, Cpn60 performs a large list of folding-independent functions, including roles in the transmission of viruses from insects to plants and stimulation of the immune system, among others. In addition to the innovation promoted by gene duplication, I discuss that the Cpn60 protein comprises a hidden amino acid combinatorial code that may well be responsible for its ability to develop novel functions while maintaining an optimized folding ability. The present review points to a complex model of evolution of protein moonlighting.
MiRNAs have emerged as key regulators of stress response in plants, suggesting their potential as candidates for knock-in/out to improve stress tolerance in agricultural crops. Although diverse ...assays have been performed, systematic and detailed studies of miRNA expression and function during exposure to multiple environments in crops are limited.
Here, we present such pioneering analysis in melon plants in response to seven biotic and abiotic stress conditions. Deep-sequencing and computational approaches have identified twenty-four known miRNAs whose expression was significantly altered under at least one stress condition, observing that down-regulation was preponderant. Additionally, miRNA function was characterized by high scale degradome assays and quantitative RNA measurements over the intended target mRNAs, providing mechanistic insight. Clustering analysis provided evidence that eight miRNAs showed a broad response range under the stress conditions analyzed, whereas another eight miRNAs displayed a narrow response range. Transcription factors were predominantly targeted by stress-responsive miRNAs in melon. Furthermore, our results show that the miRNAs that are down-regulated upon stress predominantly have as targets genes that are known to participate in the stress response by the plant, whereas the miRNAs that are up-regulated control genes linked to development.
Altogether, this high-resolution analysis of miRNA-target interactions, combining experimental and computational work, Illustrates the close interplay between miRNAs and the response to diverse environmental conditions, in melon.
These studies demonstrate that CSF‐1 and IL‐34 are conserved in birds, and uses evolutionary comparisons to infer structure function relationships among vertebrate animals.
Macrophages are involved ...in many aspects of development, host defense, pathology, and homeostasis. Their normal differentiation, proliferation, and survival are controlled by CSF‐1 via the activation of the CSF1R. A recently discovered cytokine, IL‐34, was shown to bind the same receptor in humans. Chicken is a widely used model organism in developmental biology, but the factors that control avian myelopoiesis have not been identified previously. The CSF‐1, IL‐34, and CSF1R genes in chicken and zebra finch were identified from respective genomic/cDNA sequence resources. Comparative analysis of the avian CSF1R loci revealed likely orthologs of mammalian macrophage‐specific promoters and enhancers, and the CSF1R gene is expressed in the developing chick embryo in a pattern consistent with macrophage‐specific expression. Chicken CSF‐1 and IL‐34 were expressed in HEK293 cells and shown to elicit macrophage growth from chicken BM cells in culture. Comparative sequence and co‐evolution analysis across all vertebrates suggests that the two ligands interact with distinct regions of the CSF1R. These studies demonstrate that there are two separate ligands for a functional CSF1R across all vertebrates.
Biological systems are resistant to perturbations caused by the environment and by the intrinsic noise of the system. Robustness to mutations is a particular aspect of robustness in which the ...phenotype is resistant to genotypic variation. Mutational robustness has been linked to the ability of the system to generate heritable genetic variation (a property known as evolvability). It is known that greater robustness leads to increased evolvability. Therefore, mechanisms that increase mutational robustness fuel evolvability. Two such mechanisms, molecular chaperones and gene duplication, have been credited with enormous importance in generating functional diversity through the increase of system's robustness to mutational insults. However, the way in which such mechanisms regulate robustness remains largely uncharacterized. In this review, I provide evidence in support of the role of molecular chaperones and gene duplication in innovation. Specifically, I present evidence that these mechanisms regulate robustness allowing unstable systems to survive long periods of time, and thus they provide opportunity for other mutations to compensate the destabilizing effects of functionally innovative mutations. The findings reported in this study set new questions with regards to the synergy between robustness mechanisms and how this synergy can alter the adaptive landscape of proteins. The ideas proposed in this article set the ground for future research in the understanding of the role of robustness in evolution.
•Mutational robustness leads to higher heritable genetic variation (evolvability).•Mechanisms that increase mutational robustness increase cryptic genetic variation.•Gene duplication provides genetic redundancy and mutational robustness.•Molecular chaperones capacitate innovations through canalizing genetic variation.•Chaperones and duplications have driven biological diversification and complexity.
Comparison of the proteins of thermophilic, mesophilic, and psychrophilic prokaryotes has revealed several features characteristic to proteins adapted to high temperatures, which increase their ...thermostability. These characteristics include a profusion of disulfide bonds, salt bridges, hydrogen bonds, and hydrophobic interactions, and a depletion in intrinsically disordered regions. It is unclear, however, whether such differences can also be observed in eukaryotic proteins or when comparing proteins that are adapted to temperatures that are more subtly different. When an organism is exposed to high temperatures, a subset of its proteins is overexpressed (heat-induced proteins), whereas others are either repressed (heat-repressed proteins) or remain unaffected. Here, we determine the expression levels of all genes in the eukaryotic model system
at 22 and 37 °C, and compare both the amino acid compositions and levels of intrinsic disorder of heat-induced and heat-repressed proteins. We show that, compared to heat-repressed proteins, heat-induced proteins are enriched in electrostatically charged amino acids and depleted in polar amino acids, mirroring thermophile proteins. However, in contrast with thermophile proteins, heat-induced proteins are enriched in intrinsically disordered regions, and depleted in hydrophobic amino acids. Our results indicate that temperature adaptation at the level of amino acid composition and intrinsic disorder can be observed not only in proteins of thermophilic organisms, but also in eukaryotic heat-induced proteins; the underlying adaptation pathways, however, are similar but not the same.
The population genetic mechanisms governing the preservation of gene duplicates, especially in the critical very initial phase, have remained largely unknown. Here, we demonstrate that gene ...duplication confers per se a weak selective advantage in scenarios of fitness trade-offs. Through a precise quantitative description of a model system, we show that a second gene copy serves to reduce gene expression inaccuracies derived from pervasive molecular noise and suboptimal gene regulation. We then reveal that such an accuracy in the phenotype yields a selective advantage in the order of 0.1% on average, which would allow the positive selection of gene duplication in populations with moderate/large sizes. This advantage is greater at higher noise levels and intermediate concentrations of the environmental molecule, when fitness trade-offs become more evident. Moreover, we discuss how the genome rearrangement rates greatly condition the eventual fixation of duplicates. Overall, our theoretical results highlight an original adaptive value for cells carrying new-born duplicates, broadly analyze the selective conditions that determine their early fates in different organisms, and reconcile population genetics with evolution by gene duplication.
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