scholarly journals Integrated structural and evolutionary analysis reveals common mechanisms underlying adaptive evolution in mammals

2020 ◽  
Vol 117 (11) ◽  
pp. 5977-5986 ◽  
Author(s):  
Greg Slodkowicz ◽  
Nick Goldman
Keyword(s):  
Positive Selection ◽  
Adaptive Evolution ◽  
Evolutionary Biology ◽  
Molecular Mechanisms ◽  
Structural Information ◽  
Protein Structures ◽  
Unexpected Finding ◽  
Evolutionary Analysis ◽  
Genomic Scale ◽  
Evolution Of Mammals

Understanding the molecular basis of adaptation to the environment is a central question in evolutionary biology, yet linking detected signatures of positive selection to molecular mechanisms remains challenging. Here we demonstrate that combining sequence-based phylogenetic methods with structural information assists in making such mechanistic interpretations on a genomic scale. Our integrative analysis shows that positively selected sites tend to colocalize on protein structures and that positively selected clusters are found in functionally important regions of proteins, indicating that positive selection can contravene the well-known principle of evolutionary conservation of functionally important regions. This unexpected finding, along with our discovery that positive selection acts on structural clusters, opens previously unexplored strategies for the development of better models of protein evolution. Remarkably, proteins where we detect the strongest evidence of clustering belong to just two functional groups: Components of immune response and metabolic enzymes. This gives a coherent picture of pathogens and xenobiotics as important drivers of adaptive evolution of mammals.

scholarly journals Integrated evolutionary and structural analysis reveals xenobiotics and pathogens as the major drivers of mammalian adaptation

2019 ◽  
Author(s):  
Greg Slodkowicz ◽  
Nick Goldman
Keyword(s):  
Immune Response ◽  
Positive Selection ◽  
Evolutionary Biology ◽  
Molecular Mechanisms ◽  
Structural Information ◽  
Protein Structures ◽  
Unexpected Finding ◽  
Genomic Scale ◽  
Evolution Of Mammals ◽  
New Strategies

AbstractUnderstanding the molecular basis of adaptation to the environment is a central question in evolutionary biology, yet linking detected signatures of positive selection to molecular mechanisms remains challenging. Here we demonstrate that combining sequence-based phylogenetic methods with structural information assists in making such mechanistic interpretations on a genomic scale. Our integrative analysis shows that positively selected sites tend to co-localise on protein structures and that positively selected clusters are found in functionally important regions of proteins, indicating that positive selection can contravene the well-known principle of evolutionary conservation of functionally important regions. This unexpected finding, along with our discovery that positive selection acts on structural clusters, opens new strategies for the development of better models of protein evolution. Remarkably, proteins where we detect the strongest evidence of clustering belong to just two functional groups: components of immune response and metabolic enzymes. This gives a coherent picture of immune response and xenobiotic metabolism as the drivers of adaptive evolution of mammals.

scholarly journals Streamlined use of protein structures in variant analysis

2021 ◽  
Author(s):  
Sandeep Kaur ◽  
Neblina Sikta ◽  
Andrea Schafferhans ◽  
Nicola Bordin ◽  
Mark J. Cowley ◽  
...  
Keyword(s):  
Protein Function ◽  
Molecular Mechanisms ◽  
Structural Information ◽  
Protein Structures ◽  
Structural Data ◽  
Supplementary Information ◽  
3D Structures ◽  
Link Type ◽  
Variant Analysis ◽  
Many Sources

AbstractMotivationVariant analysis is a core task in bioinformatics that requires integrating data from many sources. This process can be helped by using 3D structures of proteins, which can provide a spatial context that can provide insight into how variants affect function. Many available tools can help with mapping variants onto structures; but each has specific restrictions, with the result that many researchers fail to benefit from valuable insights that could be gained from structural data.ResultsTo address this, we have created a streamlined system for incorporating 3D structures into variant analysis. Variants can be easily specified via URLs that are easily readable and writable, and use the notation recommended by the Human Genome Variation Society (HGVS). For example, ‘https://aquaria.app/SARS-CoV-2/S/?N501Y’ specifies the N501Y variant of SARS-CoV-2 S protein. In addition to mapping variants onto structures, our system provides summary information from multiple external resources, including COSMIC, CATH-FunVar, and PredictProtein. Furthermore, our system identifies and summarizes structures containing the variant, as well as the variant-position. Our system supports essentially any mutation for any well-studied protein, and uses all available structural data — including models inferred via very remote homology — integrated into a system that is fast and simple to use. By giving researchers easy, streamlined access to a wealth of structural information during variant analysis, our system will help in revealing novel insights into the molecular mechanisms underlying protein function in health and disease.AvailabilityOur resource is freely available at the project home page (https://aquaria.app). After peer review, the code will be openly available via a GPL version 2 license at https://github.com/ODonoghueLab/Aquaria. PSSH2, the database of sequence-to-structure alignments, is also freely available for download at https://zenodo.org/record/[email protected] informationNone.

Adaptive Evolution

2003 ◽  
Author(s):  
Mary Jane West-Eberhard
Keyword(s):  
Adaptive Evolution ◽  
Evolutionary Biology ◽  
Adaptive Design ◽  
Late Nineteenth Century ◽  
Evolutionary Analysis ◽  
Developmental Constraint ◽  
Heritable Variation ◽  
Phylogenetic Constraint ◽  
Long Time ◽  
As If

Adaptive evolution—phenotypic improvement due to selection—is the central theme of Darwinian evolutionary biology. The concept of adaptive evolution by selection on heritable variation underlies every evolutionary analysis of form, function, and fitness. How biologists view adaptive evolution— how they are taught to view it—has a profound influence on thinking and research in virtually every area of biology. Despite the importance of adaptive evolution, there is still controversy over how to relate development and selection in discussions of adaptive design (e.g. see Charlesworth, 1990; Amundson, 1996). It is a controversy that began in the late nineteenth century, when biologists unfortunately began to dichotomize development and selection, as if they were opposing factors in evolution (see the discussion of gradualism in chapter 24). The modern version of this debate dichotomizes selection and developmental constraints (e.g., see Maynard Smith et al., 1985; Bell, 1989; Ridley, 1993; Amundson, 1996; see also chapter 1). Phylogenetic constraint is another version of developmental constraint, since it refers to limits imposed by ancestry (inherited developmental patterns) on current form as does the idea of developmental constraint. The dichotomy between selection and development, as if they were opposed factors in adaptive evolution, is misconceived. Adaptive evolution is a two-step process: first the generation of variation by development, then the screening of that variation by selection (Mayr, 1962; Endler and McLellan, 1988, p. 395). If an established trait (one widespread in a population) persists through phylogenetic branching events, this is not evidence against selection as an explanation for the trait (cf. Coddington, 1988), as if speciation reduces the importance of selection. Rather, it could be taken as evidence that selection is important for maintenance of the trait in more than one lineage: trait persistence over long time spans certainly does not represent absence of continued selection, since it is known that traits no longer favored by selection, such as the eyes of cave animals and walking limbs in whales, are often lost (for other classic examples, see Rensch, 1960).

scholarly journals A Genome-Wide Identification of Genes Undergoing Recombination and Positive Selection inNeisseria

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Dong Yu ◽  
Yuan Jin ◽  
Zhiqiu Yin ◽  
Hongguang Ren ◽  
Wei Zhou ◽  
...  
Keyword(s):  
Positive Selection ◽  
Adaptive Evolution ◽  
Molecular Mechanisms ◽  
Acid Sites ◽  
Gram Negative Bacteria ◽  
Orthologous Genes ◽  
Genome Wide ◽  
A Genome ◽  
History Of ◽  
Functional Analyses

Currently, there is particular interest in the molecular mechanisms of adaptive evolution in bacteria.Neisseriais a genus of gram negative bacteria, and there has recently been considerable focus on its two human pathogenic speciesN. meningitidisandN. gonorrhoeae. Until now, no genome-wide studies have attempted to scan for the genes related to adaptive evolution. For this reason, we selected 18Neisseriagenomes (14N. meningitidis, 3N. gonorrhoeaeand 1 commensalN. lactamics) to conduct a comparative genome analysis to obtain a comprehensive understanding of the roles of natural selection and homologous recombination throughout the history of adaptive evolution. Among the 1012 core orthologous genes, we identified 635 genes with recombination signals and 10 genes that showed significant evidence of positive selection. Further functional analyses revealed that no functional bias was found in the recombined genes. Positively selected genes are prone to DNA processing and iron uptake, which are essential for the fundamental life cycle. Overall, the results indicate that both recombination and positive selection play crucial roles in the adaptive evolution ofNeisseriagenomes. The positively selected genes and the corresponding amino acid sites provide us with valuable targets for further research into the detailed mechanisms of adaptive evolution inNeisseria.

scholarly journals Identification of pathogenic missense mutations using protein stability predictors

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Lukas Gerasimavicius ◽  
Xin Liu ◽  
Joseph A. Marsh
Keyword(s):  
Molecular Mechanisms ◽  
Structural Information ◽  
Protein Structures ◽  
Structural Level ◽  
Missense Mutations ◽  
Computational Stability ◽  
Pathogenic Mutations ◽  
Absolute Energy ◽  
Variant Effect ◽  
Disease Variant

Abstract Attempts at using protein structures to identify disease-causing mutations have been dominated by the idea that most pathogenic mutations are disruptive at a structural level. Therefore, computational stability predictors, which assess whether a mutation is likely to be stabilising or destabilising to protein structure, have been commonly used when evaluating new candidate disease variants, despite not having been developed specifically for this purpose. We therefore tested 13 different stability predictors for their ability to discriminate between pathogenic and putatively benign missense variants. We find that one method, FoldX, significantly outperforms all other predictors in the identification of disease variants. Moreover, we demonstrate that employing predicted absolute energy change scores improves performance of nearly all predictors in distinguishing pathogenic from benign variants. Importantly, however, we observe that the utility of computational stability predictors is highly heterogeneous across different proteins, and that they are all inferior to the best performing variant effect predictors for identifying pathogenic mutations. We suggest that this is largely due to alternate molecular mechanisms other than protein destabilisation underlying many pathogenic mutations. Thus, better ways of incorporating protein structural information and molecular mechanisms into computational variant effect predictors will be required for improved disease variant prioritisation.

scholarly journals Understanding the adaptive evolution of mitochondrial genomes in intertidal chitons

2020 ◽  
Author(s):  
Dipanjana Dhar ◽  
Debayan Dey ◽  
Soumalee Basu ◽  
Helena Fortunato
Keyword(s):  
Adaptive Evolution ◽  
Intertidal Zone ◽  
Molecular Mechanisms ◽  
Proton Translocation ◽  
Protein Structures ◽  
Dynamic Environment ◽  
Extreme Environment ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Genetic Components

AbstractMitochondria are the centre of energy metabolism in eukaryotic cells and its genes are thus key to the evolution of molecular mechanisms that metabolize cellular energy. Intertidal zone is one of the most stressful environments with extreme shifts in temperature, salinity, pH and oxygen concentrations. Marine molluscs, particularly chitons belong to the ecologically dominant organisms in this extreme environment, symbolizing an ideal model to understand mitochondrial stress adaptation. Here, we used concatenated mitochondrial genetic components separately from seven chitons of the intertidal zone to reconstruct phylogenetic relationships among these species. We performed selection analyses considering sites and branches of individual protein-coding genes to identify potentially adaptive residues and localize them in the protein structures of mt subunits. Our results exhibited significant amino acid changes in sites under diversifying selection of all the protein-coding genes, indicative of the adaptive evolution of mitochondrial genome in chitons. Furthermore, we obtained sites in the transmembrane helices lining the proton translocation channel as well as in surrounding loop regions, providing implication towards functional modification of the OXPHOS proteins essential for survival in dynamic environment of the intertidal zone.

scholarly journals Protein structure without structure determination: direct coupling analysis based on in vitro evolution

2019 ◽  
Author(s):  
Marco Fantini ◽  
Simonetta Lisi ◽  
Paolo De Los Rios ◽  
Antonino Cattaneo ◽  
Annalisa Pastore
Keyword(s):  
Structural Information ◽  
Sequence Data ◽  
Protein Structures ◽  
Direct Coupling ◽  
In Vitro Mutagenesis ◽  
Evolutionary Analysis ◽  
Protein Families ◽  
Coupling Analysis ◽  
Direct Coupling Analysis

AbstractDirect Coupling Analysis (DCA) is a powerful technique that enables to extract structural information of proteins belonging to large protein families exclusively by in silico analysis. This method is however limited by sequence availability and various biases. Here, we propose a method that exploits molecular evolution to circumvent these limitations: instead of relying on existing protein families, we used in vitro mutagenesis of TEM-1 beta lactamase combined with in vivo functional selection to generate the sequence data necessary for evolutionary analysis. We could reconstruct by this strategy, which we called CAMELS (CouplingAnalysis byMolecularEvolutionLibrarySequencing), the lactamase fold exclusively from sequence data. Through generating and sequencing large libraries of variants, we can deal with any protein, ancient or recent, from any species, having the only constraint of setting up a functional phenotypic selection of the protein. This method allows us to obtain protein structures without solving the structure experimentally.

scholarly journals The persimmon genome reveals clues to the evolution of a lineage-specific sex determination system in plants

2019 ◽  
Author(s):  
Takashi Akagi ◽  
Kenta Shirasawa ◽  
Hideki Nagasaki ◽  
Hideki Hirakawa ◽  
Ryutaro Tao ◽  
...  
Keyword(s):  
Adaptive Evolution ◽  
Molecular Mechanisms ◽  
Genetic Material ◽  
Duplication Event ◽  
Whole Genome Sequence ◽  
Autosomal Gene ◽  
Small Subset ◽  
Evolutionary Analysis ◽  
Dioecious Species ◽  
Male And Female

AbstractMost angiosperms bear hermaphroditic flowers, but a few species have evolved outcrossing strategies, such as dioecy, the presence of separate male and female individuals. We previously investigated the mechanisms underlying dioecy in diploid persimmon (D. lotus) and found that male flowers are specified by repression of the autosomal gene MeGI by its paralog, the Y-encoded pseudo-gene OGI. This mechanism is thought to be lineage-specific, but its evolutionary path remains unknown. Here, we developed a full draft of the diploid persimmon genome (D. lotus), which revealed a lineage-specific genome-wide paleoduplication event. Together with a subsequent persimmon-specific duplication(s), these events resulted in the presence of three paralogs, MeGI, OGI and newly identified Sister of MeGI (SiMeGI), from the single original gene. Evolutionary analysis suggested that MeGI underwent adaptive evolution after the paleoduplication event. Transformation of tobacco plants with MeGI and SiMeGI revealed that MeGI specifically acquired a new function as a repressor of male organ development, while SiMeGI presumably maintained the original function. Later, local duplication spawned MeGI’s regulator OGI, completing the path leading to dioecy. These findings exemplify how duplication events can provide flexible genetic material available to help respond to varying environments and provide interesting parallels for our understanding of the mechanisms underlying the transition into dieocy in plants.Author summaryPlant sexuality has fascinated scientists for decades. Most plants can self-reproduce but not all. For example, a small subset of species have evolved a system called dioecy, with separate male and female individuals. Dioecy has evolved multiple times independently and, while we do not understand the molecular mechanisms underlying dioecy in many of these species yet, a picture is starting to emerge with recent progress in several dioecious species. Here, we focused on the evolutionary events leading to dioecy in persimmon. Our previous work had identified a pair of genes regulating sex in this species, called OGI and MeGI. We drafted the whole genome sequence of diploid persimmon to investigate their evolutionary history. We discovered a lineage-specific genome duplication event, and observed that MeGI underwent adaptive evolution after this duplication. Transgenic analyses validated that MeGI newly acquired a male-suppressor function, while the other copy of this gene, SiMeGI, did not. The regulator of MeGI, OGI, resulted from a second smaller-scale duplication event, finalizing the system. This study sheds light on the role of duplication as a mechanism that promote flexible genes functions, and how it can affect important biological functions, such as the establishment of a new sexual system.

scholarly journals Identification of pathogenic missense mutations using protein stability predictors

2020 ◽  
Author(s):  
Lukas Gerasimavicius ◽  
Xin Liu ◽  
Joseph A Marsh
Keyword(s):  
Molecular Mechanisms ◽  
Structural Information ◽  
Protein Structures ◽  
Structural Level ◽  
Missense Mutations ◽  
Computational Stability ◽  
Pathogenic Mutations ◽  
Absolute Energy ◽  
Variant Effect ◽  
Disease Variant

AbstractAttempts at using protein structures to identify disease-causing mutations have been dominated by the idea that most pathogenic mutations are disruptive at a structural level. Therefore, computational stability predictors, which assess whether a mutation is likely to be stabilising or destabilising to protein structure, have been commonly used when evaluating new candidate disease variants, despite not having been developed specifically for this purpose. We therefore tested 12 different stability predictors for their ability to discriminate between pathogenic and putatively benign missense variants. We find that one method, FoldX, considerably outperforms all others in the identification of disease variants. Moreover, we demonstrate that employing absolute energy change scores improves performance of nearly all predictors. Importantly, however, we observe that the utility of computational stability predictors is highly heterogeneous across different proteins, and that they are all are inferior to the best performing variant effect predictors for identifying pathogenic mutations. We suggest that this is largely due to alternate molecular mechanisms other than protein destabilisation underlying many pathogenic mutations. Thus, better ways of incorporating protein structural information and molecular mechanisms into computational variant effect predictors will be required for improved disease variant prioritisation.

Pervasive positive selection on virus receptors driven by host-virus conflicts in mammals

2021 ◽  
Author(s):  
Wenqiang Wang ◽  
Guan-Zhu Han
Keyword(s):  
Natural Selection ◽  
Positive Selection ◽  
Adaptive Evolution ◽  
Arms Race ◽  
Cellular Proteins ◽  
Evolutionary Analysis ◽  
Interaction Interface ◽  
Virus Interaction ◽  
Elevated Rate ◽  
Viral Receptors

Viruses hijack cellular proteins known as viral receptors to initiate their infection. Viral receptors are subject to two conflicting directional forces, namely negative selection to maintain their cellular function and positive selection resulted from everchanging host-virus arms race. Much remains unclear how viral receptors evolved in mammals, and whether viral receptors from different mammal groups experienced different strength of natural selection. Here, we perform evolutionary analyses of 92 viral receptors in five major orders of mammals, including Carnivora, Cetartiodactyla, Chiroptera, Primates, and Rodentia. In all the five mammal orders, signals of positive selection are detected for a high proportion of viral receptors (from 41% in Carnivora to 65% in Rodentia). Many positively selected residues overlap host-virus interaction interface. Compared with control genes, we find viral receptors underwent elevated rate of adaptive evolution in all the five mammal orders, suggesting that host-virus conflicts are the main driver of the adaptive evolution of viral receptors in mammals. Interestingly, the overall strength of natural selection acting on viral receptors driven by host-virus arms race is largely homogenous and correlated among different mammal orders with bats and rodents, zoonosis reservoirs of importance, unexceptional. Taken together, our findings indicate host-virus conflicts have driven the elevated rate of adaptive evolution in viral receptors across mammals, and might have important implications in zoonosis surveillance and prediction. Importance Viral receptors are cellular proteins hijacked by viruses to help their infections. A complete picture on the evolution of viral receptors in mammals is still lacking. Here, we perform a comprehensive evolutionary analysis of the evolution of 92 viral receptors in five mammal orders, including Carnivora, Cetartiodactyla, Chiroptera, Primates, and Rodentia. We find that positive selection pervasively occurred during the evolution of viral receptors, and viral receptors exhibit at an elevated rate of adaptive evolution than control genes in all the five mammal orders, suggesting host-virus conflicts are a major driver of the adaptive evolution of viral receptors. Interestingly, the strength of positive selection acting on viral receptors is similar among the five mammal orders. Our study might have important implications in understanding the evolution of host-virus interaction.

Sign in / Sign up

Export Citation Format

Share Document