Host-Virus Arms Races Drive Elevated Adaptive Evolution in Viral Receptors

ABSTRACT Viral receptors are the cell surface proteins that are hijacked by viruses to initialize their infections. Viral receptors are subject to two conflicting directional forces, namely, negative selection due to functional constraints and positive selection due to host-virus arms races. It remains largely obscure whether negative pleiotropy limits the rate of adaptation in viral receptors. Here, we perform evolutionary analyses of 96 viral receptor genes in primates and find that 41 out of 96 viral receptors experienced adaptive evolution. Many positively selected residues in viral receptors are located at the virus-receptor interfaces. Compared with control proteins, viral receptors exhibit significantly elevated rate of adaptation. Further analyses of genetic polymorphisms in human populations reveal signals of positive selection and balancing selection for 53 and 5 viral receptors, respectively. Moreover, we find that 49 viral receptors experienced different selection pressures in different human populations, indicating that viruses represent an important driver of local adaptation in humans. Our findings suggest that diverse viruses, many of which have not been known to infect nonhuman primates, have maintained antagonistic associations with primates for millions of years, and the host-virus conflicts drive accelerated adaptive evolution in viral receptors. IMPORTANCE Viruses hijack cellular proteins, termed viral receptors, to assist their entry into host cells. While viral receptors experience negative selection to maintain their normal functions, they also undergo positive selection due to an everlasting evolutionary arms race between viruses and hosts. A complete picture on how viral receptors evolve under two conflicting forces is still lacking. In this study, we systematically analyzed the evolution of 96 viral receptors in primates and human populations. We found around half of viral receptors underwent adaptive evolution and exhibit significantly elevated rates of adaptation compared to control genes in primates. We also found signals of past natural selection for 58 viral receptors in human populations. Interestingly, 49 viral receptors experienced different selection pressures in different human populations, indicating that viruses represent an important driver of local adaptation in humans. Our results suggest that host-virus arms races drive accelerated adaptive evolution in viral receptors.

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Revisiting the evolutionary analysis of mammalian CRISPs reveals positive selection

10.1101/266940 ◽

2018 ◽

Author(s):

Alberto Vicens ◽

Claudia Treviño

Keyword(s):

Positive Selection ◽

Adaptive Evolution ◽

Negative Selection ◽

Secretory Proteins ◽

Evolutionary Analysis ◽

Episodic Selection ◽

Show Evidence ◽

Selection For ◽

Related Proteins

AbstractCysteine-rich secretory proteins (CRISPs) constitute a versatile family, with functions that include being components of reptilian venom and participation in mammalian reproduction. While non-mammalian vertebrates express a single CRISP gene, mammals generally express three CRISP paralogs. A previous study assessing the molecular evolution of vertebrate CRISPs revealed strong positive selection in reptilian CRISP and negative selection in mammalian CRISPs. In this study, we re-assessed molecular adaptation of mammalian CRISPs through an analysis of larger sequence datasets that represent mammalian diversity. Our analyses show evidence of recent episodes of positive selection for all mammalian CRISPs. Intensity of positive selection was heterogeneous both among CRISP paralogs (being stronger in CRISP3 than in CRISP1 and CRISP2) and across functional domains (having more impact on CRD or PR-1 domain). Analysis of episodic selection did not yield strong signatures of adaptive evolution in any particular mammalian group, suggesting that positive selection was more pervasive on mammalian CRISPs. Our findings provide evidence of adaptive evolution in a family of reproduction-related proteins, and offer interesting insights regarding the role of mammalian CRISPs in fertility and speciation.

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Selection Pressures on RNA Sequences and Structures

Evolutionary Bioinformatics ◽

10.1177/1176934319871919 ◽

2019 ◽

Vol 15 ◽

pp. 117693431987191 ◽

Cited By ~ 2

Author(s):

Katja Nowick ◽

Maria Beatriz Walter Costa ◽

Christian Höner zu Siederdissen ◽

Peter F Stadler

Keyword(s):

Positive Selection ◽

Negative Selection ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Rna Sequences ◽

Selection Pressures ◽

Evolutionary Studies ◽

Species Evolution ◽

Selection Of

With the discovery of increasingly more functional noncoding RNAs (ncRNAs), it becomes eminent to more strongly consider them as important players during species evolution. Although tests for negative selection of ncRNAs already exist since the beginning of this century, the SSS-test is the first one for also investigating positive selection. When analyzing selection in ncRNAs, it should be taken into account that selection pressures can independently act on sequence and structure. We applied the SSS-test to explore the evolution of ncRNAs in primates and identified more than 100 long noncoding RNAs (lncRNAs) that might evolve under positive selection in humans. With this test, it is now possible to more thoroughly include ncRNAs into evolutionary studies.

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Paradoxical Signaling Pathways in Developing Thymocytes

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j3cg6g ◽

2011 ◽

Vol 14 (3) ◽

pp. 378 ◽

Cited By ~ 2

Author(s):

Aws Alshamsan

Keyword(s):

Cell Death ◽

Positive Selection ◽

Cell Fate ◽

Negative Selection ◽

Mapk Pathway ◽

Erk Activation ◽

Selection For ◽

Kinetics Of ◽

Level Order

ABSTRACT- Thymocytes are subjected to processes of selection during their life in the thymus; negative selection for autoreactive thymocytes and positive selection for self-MHC restricted self-tolerant cells. Interestingly, signals for positive or negative selection originate from the same receptor. More importantly, evidence showed that both death and survival signals are mediated by the MAPK pathway. The degree and order of ERK activation, but not other MAPK proteins, has been found to be different in either cases of cell fate. Therefore, it is suspected that the kinetics of ERK after activation may dictate cell death or survival. There are two important GEF proteins that are involved in Ras/ERK activation, RasGRP and SOS. It is thought that the level, order and kinetics of ERK are influenced upstream by the type of GEF. This review discusses the role of both GEF proteins in positive and negative selection and how this reflects on ERK activation. This article is open POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Can Nitrogen Excretion of Dairy Cows Be Reduced by Genetic Selection for Low Milk Urea Nitrogen Concentration?

Animals ◽

10.3390/ani11030737 ◽

2021 ◽

Vol 11 (3) ◽

pp. 737

Author(s):

Hewa Bahithige Pavithra Chathurangi Ariyarathne ◽

Martin Correa-Luna ◽

Hugh Blair ◽

Dorian Garrick ◽

Nicolas Lopez-Villalobos

Keyword(s):

Positive Selection ◽

Milk Production ◽

Negative Selection ◽

Selection Index ◽

Nitrogen Excretion ◽

N Leaching ◽

Urea Nitrogen ◽

Milk Urea ◽

Selection For ◽

Milk Urea Nitrogen

The objectives of this study were two-fold. Firstly, to estimate the likely correlated responses in milk urea nitrogen (MUN) concentration, lactation yields of milk (MY), fat (FY) and crude protein (CPY) and mature cow liveweight (LWT) under three selection scenarios which varied in relative emphasis for MUN; 0% relative emphasis (MUN0%: equivalent to current New Zealand breeding worth index), and sign of the economic value; 20% relative emphasis positive selection (MUN+20%), and 20% relative emphasis negative selection (MUN−20%). Secondly, to estimate for these three scenarios the likely change in urinary nitrogen (UN) excretion under pasture based grazing conditions. The predicted genetic responses per cow per year for the current index were 16.4 kg MY, 2.0 kg FY, 1.4 kg CPY, −0.4 kg LWT and −0.05 mg/dL MUN. Positive selection on MUN in the index resulted in annual responses of 23.7 kg MY, 2.0 kg FY, 1.4 kg CPY, 0.6 kg LWT and 0.10 mg/dL MUN, while negative selection on MUN in the index resulted in annual responses of 5.4 kg MY, 1.6 kg FY, 1.0 kg CPY, −1.1 kg LWT and −0.17 mg/dL MUN. The MUN−20% reduced both MUN and cow productivity, whereas the MUN+20% increased MUN, milk production and LWT per cow. Per cow dry matter intake (DMI) was increased in all three scenarios as milk production increased compared to base year, therefore stocking rate (SR) was adjusted to control pasture cover. Paradoxically, ten years of selection with SR adjusted to maintain annual feed demand under the MUN+20% actually reduced per ha UN excretion by 3.54 kg, along with increases of 63 kg MY, 26 kg FY and 16 kg CPY compared to the base year. Ten years of selection on the MUN0% index generated a greater reductions of 10.45 kg UN and 30 kg MY, and increases of 32 kg FY and 21 kg CPY per ha, whereas the MUN−20% index reduced 14.06 kg UN and 136 kg MY with increases of 32 kg FY and 18 kg CPY compared to base year. All three scenarios increased partitioning of nitrogen excreted as feces. The selection index that excluded MUN was economically beneficial in the current economic circumstances over selection indices including MUN regardless of whether selection was either for or against MUN. There was no substantial benefit from an environmental point of view from including MUN in the Breeding Worth index, because N leaching is more a function of SR rather than of individual cow UN excretion. This study demonstrates that attention needs to be paid to the whole system consequences of selection for environmental outcomes in pastoral grazing circumstances.

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On the Evolutionary Origins of Obesity: A New Hypothesis

Endocrinology ◽

10.1210/en.2013-2103 ◽

2014 ◽

Vol 155 (5) ◽

pp. 1573-1588 ◽

Cited By ~ 64

Author(s):

Dyan Sellayah ◽

Felino R. Cagampang ◽

Roger D. Cox

Keyword(s):

Energy Storage ◽

Positive Selection ◽

Developed Countries ◽

Industrialized Countries ◽

Modern Humans ◽

Selection Pressures ◽

Evolutionary Origins ◽

The Metabolic Syndrome ◽

Selection For ◽

The Impact

Obesity is an escalating threat of pandemic proportions, currently affecting billions of people worldwide and exerting a devastating socioeconomic influence in industrialized countries. Despite intensive efforts to curtail obesity, results have proved disappointing. Although it is well recognized that obesity is a result of gene-environment interactions and that predisposition to obesity lies predominantly in our evolutionary past, there is much debate as to the precise nature of how our evolutionary past contributed to obesity. The “thrifty genotype” hypothesis suggests that obesity in industrialized countries is a throwback to our ancestors having undergone positive selection for genes that favored energy storage as a consequence of the cyclical episodes of famine and surplus after the advent of farming 10 000 years ago. Conversely, the “drifty genotype” hypothesis contends that the prevalence of thrifty genes is not a result of positive selection for energy-storage genes but attributable to genetic drift resulting from the removal of predative selection pressures. Both theories, however, assume that selection pressures the ancestors of modern humans living in western societies faced were the same. Moreover, neither theory adequately explains the impact of globalization and changing population demographics on the genetic basis for obesity in developed countries, despite clear evidence for ethnic variation in obesity susceptibility and related metabolic disorders. In this article, we propose that the modern obesity pandemic in industrialized countries is a result of the differential exposure of the ancestors of modern humans to environmental factors that began when modern humans left Africa around 70 000 years ago and migrated through the globe, reaching the Americas around 20 000 years ago. This article serves to elucidate how an understanding of ethnic differences in genetic susceptibility to obesity and the metabolic syndrome, in the context of historic human population redistribution, could be used in the treatment of obesity in industrialized countries.

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Human local adaptation of the TRPM8 cold receptor along a latitudinal cline

10.1101/251033 ◽

2018 ◽

Author(s):

Felix M. Key ◽

Muslihudeen A. Abdul-Aziz ◽

Roger Mundry ◽

Benjamin M Peter ◽

Aarthi Sekar ◽

...

Keyword(s):

Ambient Temperature ◽

Positive Selection ◽

Local Adaptation ◽

Genetic Variant ◽

Allele Frequencies ◽

Population Substructure ◽

Human Populations ◽

Latitudinal Cline ◽

Standing Variation ◽

Wide Range

AbstractAmbient temperature is a critical environmental factor for all living organisms. It was likely an important selective force as modern humans recently colonized temperate and cold Eurasian environments. Nevertheless, as of yet we have limited evidence of local adaptation to ambient temperature in populations from those environments. To shed light on this question, we exploit the fact that humans are a cosmopolitan species that inhabits territories under a wide range of temperatures. Focusing on cold perception – which is central to thermoregulation and survival in cold environments— we show evidence of recent local adaptation on TRPM8. This gene encodes for a cation channel that is, to date, the only temperature receptor known to mediate an endogenous response to moderate cold. The upstream variant rs10166942 shows extreme population differentiation, with frequencies that range from 5% in Nigeria to 88% in Finland (placing this SNP in the 0.02% tail of the FST empirical distribution). When all populations are jointly analysed, allele frequencies correlate with latitude and temperature beyond what can be explained by shared ancestry and population substructure. Using a Bayesian approach, we infer that the allele originated and evolved neutrally in Africa, while positive selection raised its frequency to different degrees in Eurasian populations, resulting in allele frequencies that follow a latitudinal cline. We infer strong positive selection, in agreement with ancient DNA showing high frequency of the allele in Europe 3,000 to 8,000 years ago. rs10166942 is important phenotypically because its ancestral allele is protective of migraine. This debilitating disorder varies in prevalence across human populations, with highest prevalence in individuals of European descent –precisely the population with the highest frequency of rs10166942 derived allele. We thus hypothesize that local adaptation on previously neutral standing variation may have contributed to the genetic differences that exist in the prevalence of migraine among human populations today.Author SummarySome human populations were likely under strong pressure to adapt biologically to cold climates during their colonization of non-African territories in the last 50,000 years. Such putative adaptations required genetic variation in genes that could mediate adaptive responses to cold. TRPM8 is potentially one such gene, being the only known receptor for the sensation of moderate cold temperature. We show that a likely regulatory genetic variant nearby TRPM8 has several signatures of positive selection rising its frequency in Eurasian populations during the last 25,000 years. While the genetic variant was and is rare in Africa, it is now common outside of Africa, with frequencies that strongly correlate with latitude and are highest in northern European populations. Interestingly, this same genetic variant has previously been strongly associated with migraine. This suggests that adaptation to cold has potentially contributed to the variation in migraine prevalence that exists among human groups today.

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Clonal deletion induced by either radioresistant thymic host cells or lymphohemopoietic donor cells at different stages of class I-restricted T cell ontogeny.

Journal of Experimental Medicine ◽

10.1084/jem.175.5.1277 ◽

1992 ◽

Vol 175 (5) ◽

pp. 1277-1283 ◽

Cited By ~ 43

Author(s):

D E Speiser ◽

H Pircher ◽

P S Ohashi ◽

D Kyburz ◽

H Hengartner ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Positive Selection ◽

Negative Selection ◽

Host Cells ◽

Thymic Epithelial Cells ◽

Clonal Deletion ◽

Mhc Molecules ◽

Donor Cells ◽

Self Antigens

Major histocompatibility complex (MHC) products and self-antigens expressed in the thymus determine the repertoire of mature alpha/beta T cells. While positive selection of self-MHC-restricted T cells is directed by MHC molecules expressed by thymic epithelial cells, negative selection depends to a large extent on self-antigens presented by lymphohemopoietic cells. However, radioresistant components of the thymus also influence negative selection, but it remains controversial whether this is accomplished by clonal deletion, clonal anergy, or other mechanisms. In this study, T cell development in mice expressing a transgenic T cell receptor (TCR) specific for lymphocytic choriomeningitis virus (LCMV) plus H-2Db was analyzed in the presence or absence of the viral antigen. A novel approach to analyze the thymic tissue requirements for negative selection was possible by comparing thymocyte selection in H-2Db versus H-2Dbm13 mice, since the latter allowed positive selection but not LCMV-specific deletion of transgenic TCR-expressing thymocytes. In irradiation bone marrow chimeras expressing the restriction element for negative selection (H-2Db) on host tissue, we show that radioresistant recipient cells in the thymus deleted developing T cells at an early stage of differentiation. In contrast, chimeras expressing H-2Db on lymphohemopoietic donor cells showed clonal deletion at a later stage during ontogeny.

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Phylogenetic evidence for adaptive evolution of dengue viruses in nature

Journal of General Virology ◽

10.1099/0022-1317-83-7-1679 ◽

2002 ◽

Vol 83 (7) ◽

pp. 1679-1689 ◽

Cited By ~ 91

Author(s):

S. Susanna Twiddy ◽

Christopher H. Woelk ◽

Edward C. Holmes

Keyword(s):

Amino Acid ◽

Positive Selection ◽

Adaptive Evolution ◽

Cell Tropism ◽

Structural Genes ◽

Selection Pressures ◽

Maximum Likelihood Approach ◽

E Protein ◽

Natural Isolates ◽

Likelihood Approach

A maximum-likelihood approach was used to analyse selection pressures acting on genes from all four serotypes of dengue virus (DEN). A number of amino acid positions were identified within the envelope (E) glycoprotein that have been subject to relatively weak positive selection in both DEN-3 and DEN-4, as well as in two of the five genotypes of DEN-2. No positive selection was detected in DEN-1. In accordance with the function of the E protein as the major antigenic determinant of DEN, the majority of these sites were located in, or near to, potential T- or B-cell epitopes. A smaller number of selected sites was located in other well-defined functional domains of the E protein, suggesting that cell tropism and virus-mediated membrane fusion may also confer fitness advantages to DEN in nature. Several positively selected amino acid substitutions were also identified in the NS2B and NS5 genes of DEN-2, although the cause of this selection is unclear, whereas the capsid, membrane and non-structural genes NS1, NS2A, NS3 and NS4 were all subject to strong functional constraints. Hence, evidence was found for localized adaptive evolution in natural isolates of DEN, revealing that selection pressures differ among serotypes, genotypes and viral proteins.

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Admixture-enabled selection for rapid adaptive evolution in the Americas

10.1101/783845 ◽

2019 ◽

Cited By ~ 1

Author(s):

Emily T. Norris ◽

Lavanya Rishishwar ◽

Aroon T. Chande ◽

Andrew B. Conley ◽

Kaixiong Ye ◽

...

Keyword(s):

Latin American ◽

Adaptive Evolution ◽

African Ancestry ◽

Genetic Material ◽

Human Populations ◽

Source Population ◽

Isolated Populations ◽

Independent Evidence ◽

Adaptive Immune ◽

Selection For

AbstractBackgroundAdmixture occurs when previously isolated populations come together and exchange genetic material. We hypothesized that admixture can enable rapid adaptive evolution in human populations by introducing novel genetic variants (haplotypes) at intermediate frequencies, and we tested this hypothesis via the analysis of whole genome sequences sampled from admixed Latin American populations in Colombia, Mexico, Peru, and Puerto Rico.ResultsOur screen for admixture-enabled selection relies on the identification of loci that contain more or less ancestry from a given source population than would be expected given the genome-wide ancestry frequencies. We employed a combined evidence approach to evaluate levels of ancestry enrichment at (1) single loci across multiple populations and (2) multiple loci that function together to encode polygenic traits. We found cross-population signals of African ancestry enrichment at the major histocompatibility locus on chromosome 6, consistent with admixture-enabled selection for enhanced adaptive immune response. Several of the human leukocyte antigen genes at this locus (HLA-A, HLA-DRB51 and HLA-DRB5) showed independent evidence of positive selection prior to admixture, based on extended haplotype homozygosity in African populations. A number of traits related to inflammation, blood metabolites, and both the innate and adaptive immune system showed evidence of admixture-enabled polygenic selection in Latin American populations.ConclusionsThe results reported here, considered together with the ubiquity of admixture in human evolution, suggest that admixture serves as a fundamental mechanism that drives rapid adaptive evolution in human populations.

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

Journal of Virology ◽

10.1128/jvi.01029-21 ◽

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.

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