scholarly journals Pervasive adaptation in Plasmodium-interacting proteins in mammals

2016 ◽  
Author(s):  
Emily R. Ebel ◽  
Natalie Telis ◽  
Sandeep Venkataram ◽  
Dmitri A. Petrov ◽  
David Enard
Keyword(s):  
Selective Pressure ◽  
Interacting Proteins ◽  
Mammalian Evolution ◽  
Immune Functions ◽  
Host Proteins ◽  
Mammal Species ◽  
Apicomplexan Parasites ◽  
Alpha Spectrin ◽  
Fold Excess

AbstractThe protozoan genus Plasmodium causes malaria in dozens of mammal species, including humans, non-human primates, rodents, and bats. In humans, Plasmodium infections have caused hundreds of millions of documented deaths, imposing strong selection on certain populations and driving the emergence of several resistance alleles. Over the deep timescale of mammalian evolution, however, little is known about host adaptation to Plasmodium. In this work, we expand the collection of known Plasmodium-interacting-proteins (PIPs) in mammalian hosts from ~10 to 410, by manually curating thousands of scientific abstracts. We use comparative tests of adaptation to show that PIPs have experienced >3 times more positive selection than similar mammalian proteins, consistent with Plasmodium as a major and long-standing selective pressure. PIP adaptation is strongly linked to gene expression in the blood, liver, and lung, all of which are clinically relevant tissues in Plasmodium infection. Interestingly, we find that PIPs with immune functions are especially enriched for additional interactions with viruses or bacteria, which together drive a 3.7-fold excess of adaptation. These pleiotropic interactions with unrelated pathogens, along with pressure from other Plasmodium-like Apicomplexan parasites, may help explain the PIP adaptation we observe in all clades of the mammalian tree. As a case study, we also show that alpha-spectrin, the major membrane component of mammalian red blood cells, has experienced accelerated adaptation in domains known to interact specifically with Plasmodium proteins. Similar interactions with Plasmodium-like parasites appear to have driven substantial adaptation in hundreds of host proteins throughout mammalian evolution.

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 Highly expressed proteins prefer less informative amino acids

2016 ◽  
Author(s):  
Guang-Zhong Wang
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Information Processing ◽  
Amino Acid ◽  
Copy Number ◽  
Selective Pressure ◽  
Interacting Proteins ◽  
Simple Method ◽  
Amount Of Information ◽  
Information Processing Perspective

AbstractThe transcriptional and translational systems are essentially information processing systems. However, how to quantify the amount of information decoded during expression remains a mystery. Here, we have proposed a simple method to evaluate the amount of information transcribed and translated during gene expression. We found that although proteins with a high copy number have more information translated, the average number of bits per amino acid is not high. The negative correlation between protein copy number and bits per amino acid indicates the selective pressure to reduce translational errors. Moreover, interacting proteins have similar bits per residue translated. All of these findings highlight the importance of understanding transcription and translation from an information processing perspective.

Evolutionary Pressures and Codon Bias in Low Complexity Regions of Plasmodia Parasites

2020 ◽  
Author(s):  
Andrea Cappannini ◽  
Sergio Forcelloni ◽  
Andrea Giansanti
Keyword(s):  
Evolutionary Biology ◽  
Codon Bias ◽  
Ad Hoc ◽  
Selective Pressure ◽  
Synonymous Codon ◽  
Plasmodium Species ◽  
Low Complexity ◽  
Synonymous Codon Usage ◽  
Host Proteins ◽  
Effective Number Of Codons

AbstractOne of the most debated topics in Evolutionary Biology concerns Low Complexity Regions of P. falciparum, the causative agent of the most virulent and deadly form of human malaria. In this work, we analysed the proteome of 22 plasmodium species including P. falciparum. SEG predicts that proteins containing Low Complexity Regions turn out to be longer than those which are predicted to be completely complex (without Low Complexity Regions). Moreover, using some well-known bioinformatics tools such as the Effective Number of Codons, the Pr2 and a new index that we have called SPI, we have noticed how proteins that embed Low Complexity Regions are under lower selective pressure than those that do not present this type of locus. By applying the Relative Synonymous Codon Usage and other tools developed ad hoc for this study, we note, instead, how the Low Complexity Regions appear to have a non-neutral codon bias with respect to the host proteins.

scholarly journals MicrobioLink: An Integrated Computational Pipeline to Infer Functional Effects of Microbiome–Host Interactions

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1278
Author(s):  
Tahila Andrighetti ◽  
Balazs Bohar ◽  
Ney Lemke ◽  
Padhmanand Sudhakar ◽  
Tamas Korcsmaros
Keyword(s):  
Biological Significance ◽  
Molecular Networks ◽  
Computational Pipeline ◽  
Host Proteins ◽  
Disease Pathogenesis ◽  
Host Interactions ◽  
Cellular Processes ◽  
Downstream Effects ◽  
Host Genes

Microbiome–host interactions play significant roles in health and in various diseases including autoimmune disorders. Uncovering these inter-kingdom cross-talks propels our understanding of disease pathogenesis and provides useful leads on potential therapeutic targets. Despite the biological significance of microbe–host interactions, there is a big gap in understanding the downstream effects of these interactions on host processes. Computational methods are expected to fill this gap by generating, integrating, and prioritizing predictions—as experimental detection remains challenging due to feasibility issues. Here, we present MicrobioLink, a computational pipeline to integrate predicted interactions between microbial and host proteins together with host molecular networks. Using the concept of network diffusion, MicrobioLink can analyse how microbial proteins in a certain context are influencing cellular processes by modulating gene or protein expression. We demonstrated the applicability of the pipeline using a case study. We used gut metaproteomic data from Crohn’s disease patients and healthy controls to uncover the mechanisms by which the microbial proteins can modulate host genes which belong to biological processes implicated in disease pathogenesis. MicrobioLink, which is agnostic of the microbial protein sources (bacterial, viral, etc.), is freely available on GitHub.

scholarly journals Comparison of Protective Immune Responses to Apicomplexan Parasites

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Sonja Frölich ◽  
Rolf Entzeroth ◽  
Michael Wallach
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Control Strategies ◽  
Intracellular Pathogens ◽  
Immune Functions ◽  
Alternative Control ◽  
Apicomplexan Parasites ◽  
Host Interaction ◽  
Sexual Stages ◽  
Stimulation Of

Members of the phylum Apicomplexa, which includes the speciesPlasmodium, Eimeria,Toxoplasma,andBabesiaamongst others, are the most successful intracellular pathogens known to humankind. The widespread acquisition of antimicrobial resistance to most drugs used to date has sparked a great deal of research and commercial interest in the development of vaccines as alternative control strategies. A few antigens from the asexual and sexual stages of apicomplexan development have been identified and their genes characterised; however, the fine cellular and molecular details of the effector mechanisms crucial for parasite inhibition and stimulation of protective immunity are still not entirely understood. This paper provides an overview of what is currently known about the protective immune response against the various types of apicomplexan parasites and focuses mainly on the similarities of these pathogens and their host interaction. Finally, the evolutionary relationships of these parasites and their hosts, as well as the modulation of immune functions that are critical in determining the outcome of the infection by these pathogenic organisms, are discussed.

scholarly journals Lessons from Speciation Dynamics: How to Generate Selective Pressure Towards Diversity

2015 ◽  
Vol 21 (4) ◽  
pp. 464-480 ◽  
Author(s):  
Heiko Hamann
Keyword(s):  
Selective Pressure ◽  
A Priori ◽  
Evolutionary Robotics ◽  
Search Space ◽  
Alternative Methods ◽  
A Priori Knowledge ◽  
Behavioral Diversity ◽  
Definition Of ◽  
Priori Knowledge

Recent approaches in evolutionary robotics (ER) propose to generate behavioral diversity in order to evolve desired behaviors more easily. These approaches require the definition of a behavioral distance, which often includes task-specific features and hence a priori knowledge. Alternative methods, which do not explicitly force selective pressure towards diversity (SPTD) but still generate it, are known from the field of artificial life, such as in artificial ecologies (AEs). In this study, we investigate how SPTD is generated without task-specific behavioral features or other forms of a priori knowledge and detect how methods of generating SPTD can be transferred from the domain of AE to ER. A promising finding is that in both types of systems, in systems from ER that generate behavioral diversity and also in the investigated speciation model, selective pressure is generated towards unpopulated regions of search space. In a simple case study we investigate the practical implications of these findings and point to options for transferring the idea of self-organizing SPTD in AEs to the domain of ER.

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