scholarly journals Immune genes are hotspots of shared positive selection across birds and mammals

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Allison J Shultz ◽  
Timothy B Sackton
Keyword(s):  
Positive Selection ◽  
Selective Pressure ◽  
Transcriptome Data ◽  
Evolutionary Time ◽  
Protein Coding ◽  
Immune Genes ◽  
Pathogen Challenge ◽  
Significant Enrichment ◽  
Immune Pathways ◽  
Selection For

Consistent patterns of positive selection in functionally similar genes can suggest a common selective pressure across a group of species. We use alignments of orthologous protein-coding genes from 39 species of birds to estimate parameters related to positive selection for 11,000 genes conserved across birds. We show that functional pathways related to the immune system, recombination, lipid metabolism, and phototransduction are enriched for positively selected genes. By comparing our results with mammalian data, we find a significant enrichment for positively selected genes shared between taxa, and that these shared selected genes are enriched for viral immune pathways. Using pathogen-challenge transcriptome data, we show that genes up-regulated in response to pathogens are also enriched for positively selected genes. Together, our results suggest that pathogens, particularly viruses, consistently target the same genes across divergent clades, and that these genes are hotspots of host-pathogen conflict over deep evolutionary time.

scholarly journals Immune genes are hotspots of shared positive selection across birds and mammals

2018 ◽  
Author(s):  
Allison J. Shultz ◽  
Timothy B. Sackton
Keyword(s):  
Positive Selection ◽  
Selective Pressure ◽  
Transcriptome Data ◽  
Evolutionary Time ◽  
Protein Coding ◽  
Immune Genes ◽  
Pathogen Challenge ◽  
Significant Enrichment ◽  
Immune Pathways ◽  
Selection For

Consistent patterns of positive selection in functionally similar genes can suggest a common selective pressure across a group of species. We use alignments of orthologous protein-coding genes from 39 species of birds to estimate parameters related to positive selection for 11,000 genes conserved across birds. We show that functional pathways related to the immune system, recombination, lipid metabolism, and phototransduction are enriched for positively selected genes. By comparing our results with mammalian data, we find a significant enrichment for positively selected genes shared between taxa, and that these shared selected genes are enriched for viral immune pathways. Using pathogen-challenge transcriptome data, we show that genes up-regulated in response to pathogens are also enriched for positively selected genes. Together, our results suggest that pathogens, particularly viruses, consistently target the same genes across divergent clades, and that these genes are hotspots of host-pathogen conflict over deep evolutionary time.

scholarly journals Codon-Substitution Models for Heterogeneous Selection Pressure at Amino Acid Sites

Genetics ◽  
2000 ◽  
Vol 155 (1) ◽  
pp. 431-449 ◽  
Author(s):  
Ziheng Yang ◽  
Rasmus Nielsen ◽  
Nick Goldman ◽  
Anne-Mette Krabbe Pedersen
Keyword(s):  
Amino Acid ◽  
Positive Selection ◽  
Selective Pressure ◽  
Acid Sites ◽  
Data Sets ◽  
Protein Coding ◽  
Important Indicator ◽  
Diversifying Selection ◽  
Codon Substitution ◽  
Neutral Mutations

AbstractComparison of relative fixation rates of synonymous (silent) and nonsynonymous (amino acid-altering) mutations provides a means for understanding the mechanisms of molecular sequence evolution. The nonsynonymous/synonymous rate ratio (ω = dN/dS) is an important indicator of selective pressure at the protein level, with ω = 1 meaning neutral mutations, ω < 1 purifying selection, and ω > 1 diversifying positive selection. Amino acid sites in a protein are expected to be under different selective pressures and have different underlying ω ratios. We develop models that account for heterogeneous ω ratios among amino acid sites and apply them to phylogenetic analyses of protein-coding DNA sequences. These models are useful for testing for adaptive molecular evolution and identifying amino acid sites under diversifying selection. Ten data sets of genes from nuclear, mitochondrial, and viral genomes are analyzed to estimate the distributions of ω among sites. In all data sets analyzed, the selective pressure indicated by the ω ratio is found to be highly heterogeneous among sites. Previously unsuspected Darwinian selection is detected in several genes in which the average ω ratio across sites is <1, but in which some sites are clearly under diversifying selection with ω > 1. Genes undergoing positive selection include the β-globin gene from vertebrates, mitochondrial protein-coding genes from hominoids, the hemagglutinin (HA) gene from human influenza virus A, and HIV-1 env, vif, and pol genes. Tests for the presence of positively selected sites and their subsequent identification appear quite robust to the specific distributional form assumed for ω and can be achieved using any of several models we implement. However, we encountered difficulties in estimating the precise distribution of ω among sites from real data sets.

scholarly journals The genome of Drosophila innubila reveals lineage-specific patterns of selection in immune genes

2018 ◽  
Author(s):  
Tom Hill ◽  
Boryana S. Koseva ◽  
Robert L. Unckless
Keyword(s):  
Drosophila Melanogaster ◽  
Immune System ◽  
Selective Pressure ◽  
Rapid Evolution ◽  
Toll Pathway ◽  
Pathogen Evolution ◽  
Immune Genes ◽  
Rates Of Evolution ◽  
Pathogenic Microbes ◽  
Immune Pathways

AbstractPathogenic microbes can exert extraordinary evolutionary pressure on their hosts. They can spread rapidly and sicken or even kill their host to promote their own proliferation. Because of this strong selective pressure, immune genes are some of the fastest evolving genes across metazoans, as highlighted in mammals and insects. Drosophila melanogaster serves as a powerful model for studying host/pathogen evolution. While Drosophila melanogaster are frequently exposed to various pathogens, little is known about D. melanogaster’s ecology, or if they are representative of other Drosophila species in terms of pathogen pressure. Here, we characterize the genome of Drosophila innubila, a mushroom-feeding species highly diverged from D. melanogaster and investigate the evolution of the immune system. We find substantial differences in the rates of evolution of immune pathways between D. innubila and D. melanogaster. Contrasting what was previously found for D. melanogaster, we find little evidence of rapid evolution of the antiviral RNAi genes and high rates of evolution in the Toll pathway. This suggests that, while immune genes tend to be rapidly evolving in most species, the specific genes that are fastest evolving may depend either on the pathogens faced by the host and/or divergence in the basic architecture of the host’s immune system.

scholarly journals Rapid and parallel adaptive mutations in spike S1 drive clade success in SARS-CoV-2

2021 ◽  
Author(s):  
Kathryn E. Kistler ◽  
John Huddleston ◽  
Trevor Bedford
Keyword(s):  
Positive Selection ◽  
Time Scales ◽  
Adaptive Evolution ◽  
Sequence Data ◽  
Focal Point ◽  
Comprehensive Analysis ◽  
Evolutionary Time ◽  
Evolutionary Trajectory ◽  
Protein Coding ◽  
Adaptive Mutations

AbstractDespite the appearance of variant SARS-CoV-2 viruses with altered receptorbinding or antigenic phenotypes, traditional methods for detecting adaptive evolution from sequence data do not pick up strong signals of positive selection. Here, we present a new method for identifying adaptive evolution on short evolutionary time scales with densely-sampled populations. We apply this method to SARS-CoV-2 to perform a comprehensive analysis of adaptively-evolving regions of the genome. We find that spike S1 is a focal point of adaptive evolution, but also identify positively-selected mutations in other genes that are sculpting the evolutionary trajectory of SARS-CoV-2. Protein-coding mutations in S1 are temporally-clustered and, in 2021, the ratio of nonsynonymous to synonymous divergence in S1 is more than 4 times greater than in the equivalent influenza HA1 subunit.

scholarly journals Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models

2016 ◽  
Author(s):  
Jesse D. Bloom
Keyword(s):  
Amino Acid ◽  
Positive Selection ◽  
Null Model ◽  
Biological Data ◽  
Evolutionary Patterns ◽  
Protein Coding ◽  
Site Specific ◽  
Synonymous Mutations ◽  
Influenza Hemagglutinin ◽  
Selection For

AbstractSites of positive selection are identified by comparing observed evolutionary patterns to those expected under a null model for evolution in the absence of such selection. For protein-coding genes, the most common null model is that nonsynonymous and synonymous mutations fix at equal rates; this unrealistic model has limited power to detect many interesting forms of selection. I describe a new approach that uses a null model based on high-throughput lab measurements of a gene's site-specific amino-acid preferences. This null model makes it possible to identify diversifying selection for amino-acid change and differential selection for mutations to amino acids that are unexpected given the measurements made in the lab. I show that this approach identifies sites of adaptive substitutions in four genes (lactamase, Gal4, influenza nucleoprotein, and influenza hemagglutinin) far better than a comparable method that simply compares the rates of nonsynonymous and synonymous substitutions. As rapid increases in biological data enable increasingly nuanced descriptions of the constraints on individual sites, approaches like the one here can improve our ability to identify many interesting forms of selection.

scholarly journals Evidence of Pathogen-Induced Immunogenetic Selection across the Large Geographic Range of a Wild Seabird

2020 ◽  
Vol 37 (6) ◽  
pp. 1708-1726
Author(s):  
Hila Levy ◽  
Steven R Fiddaman ◽  
Juliana A Vianna ◽  
Daly Noll ◽  
Gemma V Clucas ◽  
...  
Keyword(s):  
Geographic Range ◽  
Gentoo Penguin ◽  
Innate Immune ◽  
Evolutionary Time ◽  
Immune Genes ◽  
Changing Environments ◽  
Pathogen Challenge ◽  
Innate Immune Genes ◽  
Latitudinal Range

Abstract Over evolutionary time, pathogen challenge shapes the immune phenotype of the host to better respond to an incipient threat. The extent and direction of this selection pressure depend on the local pathogen composition, which is in turn determined by biotic and abiotic features of the environment. However, little is known about adaptation to local pathogen threats in wild animals. The Gentoo penguin (Pygoscelis papua) is a species complex that lends itself to the study of immune adaptation because of its circumpolar distribution over a large latitudinal range, with little or no admixture between different clades. In this study, we examine the diversity in a key family of innate immune genes—the Toll-like receptors (TLRs)—across the range of the Gentoo penguin. The three TLRs that we investigated present varying levels of diversity, with TLR4 and TLR5 greatly exceeding the diversity of TLR7. We present evidence of positive selection in TLR4 and TLR5, which points to pathogen-driven adaptation to the local pathogen milieu. Finally, we demonstrate that two positively selected cosegregating sites in TLR5 are sufficient to alter the responsiveness of the receptor to its bacterial ligand, flagellin. Taken together, these results suggest that Gentoo penguins have experienced distinct pathogen-driven selection pressures in different environments, which may be important given the role of the Gentoo penguin as a sentinel species in some of the world’s most rapidly changing environments.

scholarly journals Alu RNA Modulates the Expression of Cell Cycle Genes in Human Fibroblasts

2019 ◽  
Vol 20 (13) ◽  
pp. 3315 ◽  
Author(s):  
Simona Cantarella ◽  
Davide Carnevali ◽  
Marco Morselli ◽  
Anastasia Conti ◽  
Matteo Pellegrini ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Human Fibroblasts ◽  
Rna Polymerase Iii ◽  
Protein Coding ◽  
Non Coding Rna ◽  
Genome Wide ◽  
Hela Cell Lines ◽  
Significant Enrichment ◽  
Alu Rna

Alu retroelements, whose retrotransposition requires prior transcription by RNA polymerase III to generate Alu RNAs, represent the most numerous non-coding RNA (ncRNA) gene family in the human genome. Alu transcription is generally kept to extremely low levels by tight epigenetic silencing, but it has been reported to increase under different types of cell perturbation, such as viral infection and cancer. Alu RNAs, being able to act as gene expression modulators, may be directly involved in the mechanisms determining cellular behavior in such perturbed states. To directly address the regulatory potential of Alu RNAs, we generated IMR90 fibroblasts and HeLa cell lines stably overexpressing two slightly different Alu RNAs, and analyzed genome-wide the expression changes of protein-coding genes through RNA-sequencing. Among the genes that were upregulated or downregulated in response to Alu overexpression in IMR90, but not in HeLa cells, we found a highly significant enrichment of pathways involved in cell cycle progression and mitotic entry. Accordingly, Alu overexpression was found to promote transition from G1 to S phase, as revealed by flow cytometry. Therefore, increased Alu RNA may contribute to sustained cell proliferation, which is an important factor of cancer development and progression.

scholarly journals A novel positive selection for identifying cold-sensitive myosin II mutants in Dictyostelium.

Genetics ◽  
1995 ◽  
Vol 140 (2) ◽  
pp. 505-515 ◽  
Author(s):  
B Patterson ◽  
J A Spudich
Keyword(s):  
Positive Selection ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Time Scale ◽  
Myosin Ii ◽  
Rapid Onset ◽  
Chemical Mutagenesis ◽  
Wild Type ◽  
Cold Sensitive ◽  
Selection For

Abstract We developed a positive selection for myosin heavy chain mutants in Dictyostelium. This selection is based on the fact that brief exposure to azide causes wild-type cells to release from the substrate, whereas myosin null cells remain adherent. This procedure assays myosin function on a time scale of minutes and has therefore allowed us to select rapid-onset cold-sensitive mutants after random chemical mutagenesis of Dictyostelium cells. We developed a rapid technique for determining which mutations lie in sequences of the myosin gene that encode the head (motor) domain and localized 27 of 34 mutants to this domain. We recovered the appropriate sequences from five of the mutants and demonstrated that they retain their cold-sensitive properties when expressed from extrachromosomal plasmids.

scholarly journals Is formal employment sector hereditary? Determinants of formal/informal sector choice for Mexican male workers

2019 ◽  
pp. 91-121
Author(s):  
Adelaido García-Andrés ◽  
Ernesto Aguayo-Téllez ◽  
Jose N. Martínez
Keyword(s):  
Positive Selection ◽  
Social Mobility ◽  
Informal Sector ◽  
Formal Sector ◽  
Strong Connection ◽  
Employment Sector ◽  
Formal Employment ◽  
Selection For ◽  
The Relationship ◽  
Employment Choices

Understanding the relationship between parents’ and sons’ formal employment is essential for promoting social mobility in Mexico. Using the 2011 Survey of Social Mobility in Mexico (EMOVI), this paper contributes to the literature by addressing the intergenerational mobility of employment. Findings show a strong connection between intergenerational employment choices and suggest a positive selection for workers. Individuals with parents who worked in the formal sector are more likely to be enrolled in formal work and vice versa. Also, after controlling for parent’s employment sector, schooling remains as a significant vehicle to transit to the formal sector.

scholarly journals Natural Selection at an Exceptionally Long GGC Repeat in the Human RASGEF1C and Divergent Genotypes in Late-onset Neurocognitive Disorder

2021 ◽  
Author(s):  
Z Jafarian ◽  
S Khamse ◽  
H Afshar ◽  
Khorram Khorshid HR ◽  
A Delbari ◽  
...  
Keyword(s):  
Natural Selection ◽  
Evolutionary Biology ◽  
Late Onset ◽  
Core Promoter ◽  
Human Subjects ◽  
Specific Gene ◽  
Protein Coding ◽  
Repeat Allele ◽  
Complex Disorders ◽  
Selection For

Abstract Across the human protein-coding genes, the neuron-specific gene, RASGEF1C, contains the longest (GGC)-repeat, spanning its core promoter and 5′ untranslated region (RASGEF1C-201 ENST00000361132.9). RASGEF1C expression dysregulation occurs in late-onset neurocognitive disorders (NCDs), such as Alzheimer’s disease. Here we sequenced the GGC-repeat in a sample of human subjects (N = 269), consisting of late-onset NCDs (N = 115) and controls (N = 154). We also studied the status of this STR across vertebrates. The 6-repeat allele of this repeat was the predominant allele in the controls (frequency = 0.85) and NCD patients (frequency = 0.78). The NCD genotype compartment consisted of an excess of genotypes that lacked the 6-repeat (Mid-P exact = 0.004). We also detected divergent genotypes that were present in five NCD patients and not in the controls (Mid-P exact = 0.007). This STR expanded beyond 2-repeats specifically in primates, and was at maximum length in human. We conclude that there is natural selection for the 6-repeat allele of the RASGEF1C (GGC)-repeat in human, and significant divergence from that allele in late-onset NCDs. Indication of natural selection for predominantly abundant STR alleles and divergent genotypes enhance the perspective of evolutionary biology and disease pathogenesis in human complex disorders.

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