scholarly journals Viruses rule over adaptation in conserved human proteins

2019 ◽  
Author(s):  
David Castellano ◽  
Lawrence H. Uricchio ◽  
Kasper Munch ◽  
David Enard
Keyword(s):  
Adaptive Evolution ◽  
Significant Role ◽  
Host Adaptation ◽  
Arms Race ◽  
Interacting Proteins ◽  
Cellular Functions ◽  
Host Proteins ◽  
Selective Pressures ◽  
Human Proteins ◽  
Antiviral Proteins

AbstractAdaptive evolution often involves fast-evolving proteins, and the fastest-evolving proteins in primates include antiviral proteins engaged in an arms race with viruses 1-3. Even though fast-evolving antiviral proteins are the most studied cases of primate host adaptation against viruses, viruses predominantly interact with host proteins that are broadly conserved between distant species in order to complete their replication cycle 4. Broadly conserved proteins are generally viewed as playing a negligible role in adaptive evolution. Here, we used a dataset of ~4,500 human proteins known to physically interact with viruses (VIPs for Virus-Interacting Proteins), to test the involvement of broadly conserved proteins in adaptive evolution against viruses. We found that VIPs conserved between animals and fungi have experienced not only high rates of adaption, but also strong adaptive events. Broadly conserved proteins that do not interact with viruses experienced very little adaptation. As a result, the arms race with viruses explains more than 75% of adaptation in the most phylogenetically conserved subset of the human proteome. Our results imply that broadly conserved proteins have played a significant role in adaptation, and that viruses were likely one of very few selective pressures that were able to force the conserved, central pillars of host cellular functions to adapt during evolution.

scholarly journals Viruses are a dominant driver of protein adaptation in mammals

2015 ◽  
Author(s):  
David Enard ◽  
Le Cai ◽  
Carina Gwenapp ◽  
Dmitri A Petrov
Keyword(s):  
Evolutionary Change ◽  
Antiviral Defense ◽  
Interacting Proteins ◽  
Immune Functions ◽  
Functional Categories ◽  
Cellular Functions ◽  
Broad Array ◽  
Antiviral Proteins

Viruses interact with hundreds to thousands of proteins in mammals, yet adaptation against viruses has only been studied in a few proteins specialized in antiviral defense. Whether adaptation to viruses typically involves only specialized antiviral proteins or affects a broad array of proteins is unknown. Here, we analyze adaptation in ~1,300 virus-interacting proteins manually curated from a set of 9,900 proteins conserved across mammals. We show that viruses (i) use the more evolutionarily constrained proteins from the cellular functions they hijack and that (ii) despite this high constraint, virus-interacting proteins account for a high proportion of all protein adaptation in humans and other mammals. Adaptation is elevated in virus-interacting proteins across all functional categories, including both immune and non-immune functions. Our results demonstrate that viruses are one of the most dominant drivers of evolutionary change across mammalian and human proteomes.

scholarly journals Assessing evidence for adaptive evolution in two hearing-related genes important for high-frequency hearing in echolocating mammals

2021 ◽  
Author(s):  
Hui Wang ◽  
Hanbo Zhao ◽  
Yujia Chu ◽  
Jiang Feng ◽  
Keping Sun
Keyword(s):  
Adaptive Evolution ◽  
Hair Cells ◽  
High Frequency ◽  
Phylogenetic Trees ◽  
Outer Hair Cells ◽  
Functional Domain ◽  
Coding Region ◽  
Selective Pressures ◽  
Wide Range ◽  
Different Parts

Abstract High-frequency hearing is particularly important for echolocating bats and toothed whales. Previously, studies of the hearing-related genes Prestin, KCNQ4, and TMC1 documented that adaptive evolution of high-frequency hearing has taken place in echolocating bats and toothed whales. In this study, we present two additional candidate hearing-related genes, Shh and SK2, that may also have contributed to the evolution of echolocation in mammals. Shh is a member of the vertebrate Hedgehog gene family and is required in the specification of the mammalian cochlea. SK2 is expressed in both inner and outer hair cells, and it plays an important role in the auditory system. The coding region sequences of Shh and SK2 were obtained from a wide range of mammals with and without echolocating ability. The topologies of phylogenetic trees constructed using Shh and SK2 were different; however, multiple molecular evolutionary analyses showed that those two genes experienced different selective pressures in echolocating bats and toothed whales compared to non-echolocating mammals. In addition, several nominally significant positively selected sites were detected in the non-functional domain of the SK2 gene, indicating that different selective pressures were acting on different parts of the SK2 gene. This study has expanded our knowledge of the adaptive evolution of high-frequency hearing in echolocating mammals.

scholarly journals Interacting Proteins on Human Spermatozoa: Adaptive Evolution of the Binding of Semenogelin I to EPPIN

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e82014 ◽  
Author(s):  
Erick J. R. Silva ◽  
Katherine G. Hamil ◽  
Michael G. O’Rand
Keyword(s):  
Adaptive Evolution ◽  
Human Spermatozoa ◽  
Interacting Proteins

scholarly journals Elucidating the regulatory mechanism of Swi1 prion in global transcription and stress responses

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhiqiang Du ◽  
Jeniece Regan ◽  
Elizabeth Bartom ◽  
Wei-Sheng Wu ◽  
Li Zhang ◽  
...  
Keyword(s):  
Stress Responses ◽  
Regulation Of Transcription ◽  
Interacting Proteins ◽  
Environmental Stress Response ◽  
Key Factors ◽  
Cellular Functions ◽  
Beneficial Effects ◽  
Genome Wide ◽  
Genes Encoding ◽  
A Subunit

AbstractTranscriptional regulators are prevalent among identified prions in Saccharomyces cerevisiae, however, it is unclear how prions affect genome-wide transcription. We show here that the prion ([SWI+]) and mutant (swi1∆) forms of Swi1, a subunit of the SWI/SNF chromatin-remodeling complex, confer dramatically distinct transcriptomic profiles. In [SWI+] cells, genes encoding for 34 transcription factors (TFs) and 24 Swi1-interacting proteins can undergo transcriptional modifications. Several TFs show enhanced aggregation in [SWI+] cells. Further analyses suggest that such alterations are key factors in specifying the transcriptomic signatures of [SWI+] cells. Interestingly, swi1∆ and [SWI+] impose distinct and oftentimes opposite effects on cellular functions. Translation-associated activities, in particular, are significantly reduced in swi1∆ cells. Although both swi1∆ and [SWI+] cells are similarly sensitive to thermal, osmotic and drought stresses, harmful, neutral or beneficial effects were observed for a panel of tested chemical stressors. Further analyses suggest that the environmental stress response (ESR) is mechanistically different between swi1∆ and [SWI+] cells—stress-inducible ESR (iESR) are repressed by [SWI+] but unchanged by swi1∆ while stress-repressible ESR (rESR) are induced by [SWI+] but repressed by swi1∆. Our work thus demonstrates primarily gain-of-function outcomes through transcriptomic modifications by [SWI+] and highlights a prion-mediated regulation of transcription and phenotypes in yeast.

scholarly journals NAA10 p.(N101K) disrupts N-terminal acetyltransferase complex NatA and is associated with developmental delay and hemihypertrophy

2020 ◽  
Author(s):  
Nina McTiernan ◽  
◽  
Harinder Gill ◽  
Carlos E. Prada ◽  
Harry Pachajoa ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Genetic Disorders ◽  
Cellular Functions ◽  
Functional Studies ◽  
Phenotypic Spectrum ◽  
Independent Functions ◽  
Evolutionarily Conserved ◽  
Human Proteins ◽  
The Impact

Abstract Nearly half of all human proteins are acetylated at their N-termini by the NatA N-terminal acetyltransferase complex. NAA10 is evolutionarily conserved as the catalytic subunit of NatA in complex with NAA15, but may also have NatA-independent functions. Several NAA10 variants are associated with genetic disorders. The phenotypic spectrum includes developmental delay, intellectual disability, and cardiac abnormalities. Here, we have identified the previously undescribed NAA10 c.303C>A and c.303C>G p.(N101K) variants in two unrelated girls. These girls have developmental delay, but they both also display hemihypertrophy a feature normally not observed or registered among these cases. Functional studies revealed that NAA10 p.(N101K) is completely impaired in its ability to bind NAA15 and to form an enzymatically active NatA complex. In contrast, the integrity of NAA10 p.(N101K) as a monomeric acetyltransferase is intact. Thus, this NAA10 variant may represent the best example of the impact of NatA mediated N-terminal acetylation, isolated from other potential NAA10-mediated cellular functions and may provide important insights into the phenotypes observed in individuals expressing pathogenic NAA10 variants.

scholarly journals Solitary ecology as a phenomenon extending beyond insular systems: exaptive evolution in Anolis lizards

2019 ◽  
Vol 15 (5) ◽  
pp. 20190056 ◽  
Author(s):  
Julián A. Velasco ◽  
Steven Poe ◽  
Constantino González-Salazar ◽  
Oscar Flores-Villela
Keyword(s):  
Body Size ◽  
Adaptive Evolution ◽  
Environmental Filtering ◽  
Phenotypic Evolution ◽  
Phenotypic Differentiation ◽  
Evolutionary Transitions ◽  
Ecological Release ◽  
Selective Pressures ◽  
Island Species

The mechanisms driving phenotypic evolution have been of interest to biologists since Darwin. Ecological release—wherein adaptive evolution occurs following relaxation of constraining selective pressures—and environmental filtering—wherein exaptive traits allow colonization of a new area—have been studied in several insular cases. Anolis lizards, which may exist in solitude or sympatry with multiple congeners, are an excellent system for evaluating whether ecological release and environmental filtering are associated with phenotypic shifts across phylogenetic and geographical scales. Insular solitary Anolis exhibit phenotypic differentiation in body size and sexual size dimorphism—SSD—through exaptive and adaptive evolution, respectively. But, the generality of these effects has not yet been addressed. Here, we analyse the evolution of body size and SSD relative to sympatry in mainland Anolis . We found that mainland species co-occurring with few congeners exhibit uniform body size and greater SSD relative to other random mainland assemblages, consistent with the insular solitary pattern. The locations of evolutionary shifts for both traits do not coincide with evolutionary transitions to decreased levels of sympatry. These results are consistent with exaptive environmental filtering but not adaptive ecological release. Future studies should be conducted at local scales to evaluate the role of these factors in the evolution of solitary existence in mainland and island species.

scholarly journals Analysis of the cross-reactivity and of the 1.5 Å crystal structure of the Malassezia sympodialis Mala s 6 allergen, a member of the cyclophilin pan-allergen family

2006 ◽  
Vol 396 (1) ◽  
pp. 41-49 ◽  
Author(s):  
Andreas G. Glaser ◽  
Andreas Limacher ◽  
Sabine Flückiger ◽  
Annika Scheynius ◽  
Leonardo Scapozza ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Three Dimensional ◽  
Cross Reactivity ◽  
Dimensional Structure ◽  
Cellular Functions ◽  
Human Proteins ◽  
Ige Mediated ◽  
Unit Cell Dimensions

Cyclophilins constitute a family of proteins involved in many essential cellular functions. They have also been identified as a panallergen family able to elicit IgE-mediated hypersensitivity reactions. Moreover, it has been shown that human cyclophilins are recognized by serum IgE from patients sensitized to environmental cyclophilins. IgE-mediated autoreactivity to self-antigens that have similarity to environmental allergens is often observed in atopic disorders. Therefore comparison of the crystal structure of human proteins with similarity to allergens should allow the identification of structural similarities to rationally explain autoreactivity. A new cyclophilin from Aspergillus fumigatus (Asp f 27) has been cloned, expressed and showed to exhibit cross-reactivity in vitro and in vivo. The three-dimensional structure of cyclophilin from the yeast Malassezia sympodialis (Mala s 6) has been determined at 1.5 Å (1 Å=0.1 nm) by X-ray diffraction. Crystals belong to space group P41212 with unit cell dimensions of a=b=71.99 Å and c=106.18 Å. The structure was solved by molecular replacement using the structure of human cyclophilin A as the search model. The refined structure includes all 162 amino acids of Mala s 6, an active-site-bound Ala-Pro dipeptide and 173 water molecules, with a crystallographic R- and free R-factor of 14.3% and 14.9% respectively. The overall structure consists of an eight-stranded antiparallel β-barrel and two α-helices covering the top and bottom of the barrel, typical for cyclophilins. We identified conserved solvent-exposed residues in the fungal and human structures that are potentially involved in the IgE-mediated cross-reactivity.

scholarly journals Identification of Epstein-Barr Virus RK-BARF0-Interacting Proteins and Characterization of Expression Pattern

2004 ◽  
Vol 78 (23) ◽  
pp. 12848-12856 ◽  
Author(s):  
Natalie J. Thornburg ◽  
Shuichi Kusano ◽  
Nancy Raab-Traub
Keyword(s):  
Cell Lines ◽  
Epstein Barr Virus ◽  
Interacting Proteins ◽  
Cellular Functions ◽  
Barr Virus ◽  
Acid Protein ◽  
Infected Cells ◽  
Epstein Barr ◽  
Endoplasmic Reticulum Targeting

ABSTRACT The Epstein-Barr virus (EBV) BamHI A transcripts are a family of transcripts that are differentially spliced and can be detected in multiple EBV-associated malignancies. Several of the transcripts may encode proteins. One transcript of interest, RK-BARF0, is proposed to encode a 279-amino-acid protein with a possible endoplasmic reticulum-targeting sequence. In this study, the properties of RK-BARF0 were examined through identification of cellular-interacting proteins through yeast two-hybrid analysis and characterization of its expression in EBV-infected cells and tumors. In addition to the interaction previously identified with cellular Notch, it was determined that RK-BARF0 also bound cellular human I-mfa domain-containing protein (HIC), epithelin, and scramblase. An interaction between RK-BARF0 and Notch or epithelin induced proteasome-dependent degradation of Notch and epithelin but not of HIC or scramblase. Low levels of endogenous Notch expression in EBV-positive cell lines may correlate with RK-BARF0 expression. However, a screen of EBV-positive cell lines and tumors with an affinity-purified α-RK-BARF0 antiserum did not consistently detect RK-BARF0. These data suggest that while RK-BARF0 may have important cellular functions during EBV infection, and while the phenotype of EBV-positive cells suggest its expression, RK-BARF0 levels may be too low to detect.

scholarly journals A map of direct SARS-CoV-2 protein interactions implicates specific human host processes

2021 ◽  
Author(s):  
Dae-Kyum Kim ◽  
Benjamin Weller ◽  
Chung-Wen Lin ◽  
Dayag Sheykhkarimli ◽  
Jennifer J Knapp ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Membrane Trafficking ◽  
Host Protein ◽  
Host Proteins ◽  
Systematic Map ◽  
High Data ◽  
Protein Ubiquitination ◽  
Human Proteins ◽  
Physical Interactions ◽  
Key Steps

Key steps in viral propagation, immune suppression and pathology are mediated by direct, binary physical interactions between viral and host proteins. To understand the biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we generated an unbiased systematic map of binary physical interactions between viral and host interactions, complementing previous co-complex association maps by conveying more direct mechanistic understanding and enabling targeted disruption of direct interactions. To this end, we deployed two parallel strategies, identifying 205 virus-host and 27 intraviral binary interactions amongst 171 host and 19 viral proteins, with orthogonal validation by an internally benchmarked NanoLuc two-hybrid system to ensure high data quality. Host proteins interacting with SARS-CoV-2 proteins were enriched in various cellular processes, including immune signaling and inflammation, protein ubiquitination, and membrane trafficking. Specific subnetworks provide new hypotheses related to viral modulation of host protein homeostasis and T-cell regulation. The direct virus-host protein interactions we identified can now be prioritized as targets for therapeutic intervention. More generally, we provide a resource of systematic maps describing which SARS-CoV-2 and human proteins interact directly.

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