scholarly journals Rapid evolution of antiviral APOBEC3 genes driven by the conflicts with ancient retroviruses

2019 ◽  
Author(s):  
Jumpei Ito ◽  
Robert J. Gifford ◽  
Kei Sato
Keyword(s):  
Positive Selection ◽  
Gene Amplification ◽  
Rapid Evolution ◽  
Endogenous Retroviruses ◽  
New World Monkeys ◽  
Viral Dna ◽  
Tandem Gene Duplication ◽  
Strong Positive Selection ◽  
Mammalian Genomes ◽  
Apobec3 Proteins

AbstractThe evolution of antiviral genes has been fundamentally shaped by antagonistic interactions with ancestral viruses. The AID/APOBEC family genes (AID and APOBEC1-4) encode cellular cytosine deaminases that target nucleic acids and catalyze C-to-U mutations. In the case of retroviral replication, APOBEC3 proteins induce C-to-U mutations in minus-stranded viral DNA, which results in G-to-A mutations in the viral genome. Previous studies have indicated that the expansion and rapid evolution of mammalian APOBEC3 genes has been driven by an arms race with retroviral parasites, but this has not been thoroughly investigated. Endogenous retroviruses (ERVs) are retrotransposons originated from ancient retroviral infections. These sequences sometimes bear the hallmarks of APOBEC3-mediated mutations, and therefore serve as a record of the ancient conflict between retroviruses and APOBEC3 genes. Here we systematically investigated the sequences of ERVs and APOBEC3 genes in mammals to reconstruct details of the evolutionary conflict between them. We identified 1,420 AID/APOBEC family genes in a comprehensive screen of mammalian genome. Of the AID/APOBEC family genes, APOBEC3 genes have been selectively amplified in mammalian genomes and disclose evidence of strong positive selection - whereas the catalytic domain was highly conserved across species, the structure loop 7, which recognizes viral DNA/RNA substrates, was shown to be evolving under strong positive selection. Although APOBEC3 genes have been amplified by tandem gene duplication in most mammalian lineages, the retrotransposition-mediated gene amplification was found in several mammals including New World monkeys and prosimian primates. Comparative analysis revealed that G-to-A mutations are accumulated in ERVs, and that the G-to-A mutation signatures on ERVs is concordant with the target preferences of APOBEC3 proteins. Importantly, the number of APOBEC3 genes was significantly correlated with the frequency of G-to-A mutations in ERVs, suggesting that the amplification of APOBEC3 genes led to stronger attacks on ERVs and/or their ancestral retroviruses by APOBEC3 proteins. Furthermore, the numbers of APOBEC3 genes and ERVs in mammalian genomes were positively correlated, and in primates, the timings of APOBEC3 gene amplification was concordant with that of ERV invasions. Our findings suggest that conflict with ancient retroviruses was a major selective pressure driving the rapid evolution of APOBEC3 genes in mammals.

scholarly journals Retrocopying expands the functional repertoire of APOBEC3 antiviral proteins in primates

2020 ◽  
Author(s):  
Lei Yang ◽  
Michael Emerman ◽  
Harmit S. Malik ◽  
Richard N. McLaughlin
Keyword(s):  
Rapid Evolution ◽  
Endogenous Retroviruses ◽  
New World Monkeys ◽  
Restriction Factors ◽  
New Host ◽  
Arms Races ◽  
Cytidine Deaminases ◽  
Host Restriction ◽  
Host Restriction Factors ◽  
Evolution Of Viruses

AbstractHost-virus arms races are inherently asymmetric; viruses evolve much more rapidly than host genomes. Thus, there is high interest in discovering mechanisms by which host genomes keep pace with rapidly evolving viruses. One family of restriction factors, the APOBEC3 (A3) cytidine deaminases, has undergone positive selection and expansion via segmental gene duplication and recombination. Here, we show that new copies of A3 genes have also been created in primates by reverse transcriptase-encoding elements like LINE-1 or endogenous retroviruses via a process termed retrocopying. First, we discovered that all simian primate genomes retain the remnants of an ancient A3 retrocopy: A3I. Furthermore, we found that some New World monkeys encode up to ten additional APOBEC3G (A3G) retrocopies. Some of these A3G retrocopies are transcribed in a variety of tissues and able to restrict retroviruses. Our findings suggest that host genomes co-opt retroelement activity in the germline to create new host restriction factors as another means to keep pace with the rapid evolution of viruses. (163)

scholarly journals Innovation of heterochromatin functions drives rapid evolution of essential ZAD-ZNF genes in Drosophila

2020 ◽  
Author(s):  
Bhavatharini Kasinathan ◽  
Serafin U. Colmenares ◽  
Hannah McConnell ◽  
Janet M. Young ◽  
Gary H. Karpen ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Transcription Factors ◽  
Positive Selection ◽  
Larval Development ◽  
Rapid Evolution ◽  
Strong Positive Selection ◽  
General Explanation

AbstractContrary to prevailing dogma, evolutionarily young and dynamic genes can encode essential functions. Here, we investigate genetic innovation in ZAD-ZNF genes, which encode the most abundant class of insect transcription factors. We find that evolutionarily dynamic ZAD-ZNF genes are more likely to encode essential functions in Drosophila melanogaster than ancient, conserved ZAD-ZNF genes. To understand the basis of this unexpected correlation, we focus on the Nicknack ZAD-ZNF gene. Nicknack is an evolutionarily young, poorly retained in Drosophila species, and evolves under strong positive selection, yet we find that it is necessary for larval development in D. melanogaster. We show that Nicknack encodes a heterochromatin-localizing protein like its closely related paralog Oddjob, also an evolutionarily dynamic, essential ZAD-ZNF gene. We find that the divergent D. simulans Nicknack protein can still localize to D. melanogaster heterochromatin and rescue viability of female but not male Nicknack-null D. melanogaster. Our findings suggest that innovation for rapidly changing heterochromatin functions might provide a general explanation for the essential functions of many evolutionarily dynamic ZAD-ZNF genes in insects.

scholarly journals Innovation of heterochromatin functions drives rapid evolution of essential ZAD-ZNF genes in Drosophila

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Bhavatharini Kasinathan ◽  
Serafin U Colmenares ◽  
Hannah McConnell ◽  
Janet M Young ◽  
Gary H Karpen ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Transcription Factors ◽  
Positive Selection ◽  
Larval Development ◽  
Rapid Evolution ◽  
Strong Positive Selection

Contrary to dogma, evolutionarily young and dynamic genes can encode essential functions. We find that evolutionarily dynamic ZAD-ZNF genes, which encode the most abundant class of insect transcription factors, are more likely to encode essential functions in Drosophila melanogaster than ancient, conserved ZAD-ZNF genes. We focus on the Nicknack ZAD-ZNF gene, which is evolutionarily young, poorly retained in Drosophila species, and evolves under strong positive selection. Yet we find that it is necessary for larval development in D. melanogaster. We show that Nicknack encodes a heterochromatin-localizing protein like its paralog Oddjob, also an evolutionarily dynamic yet essential ZAD-ZNF gene. We find that the divergent D. simulans Nicknack protein can still localize to D. melanogaster heterochromatin and rescue viability of female but not male Nicknack-null D. melanogaster. Our findings suggest that innovation for rapidly changing heterochromatin functions might generally explain the essentiality of many evolutionarily dynamic ZAD-ZNF genes in insects.

scholarly journals Retrocopying expands the functional repertoire of APOBEC3 antiviral proteins in primates

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Lei Yang ◽  
Michael Emerman ◽  
Harmit S Malik ◽  
Richard N McLaughlin
Keyword(s):  
Rapid Evolution ◽  
Endogenous Retroviruses ◽  
New World Monkeys ◽  
Restriction Factors ◽  
New Host ◽  
Arms Races ◽  
Cytidine Deaminases ◽  
Host Restriction ◽  
Host Restriction Factors ◽  
Evolution Of Viruses

Host-virus arms races are inherently asymmetric; viruses evolve much more rapidly than host genomes. Thus, there is high interest in discovering mechanisms by which host genomes keep pace with rapidly evolving viruses. One family of restriction factors, the APOBEC3 (A3) cytidine deaminases, has undergone positive selection and expansion via segmental gene duplication and recombination. Here, we show that new copies of A3 genes have also been created in primates by reverse transcriptase-encoding elements like LINE-1 or endogenous retroviruses via a process termed retrocopying. First, we discovered that all simian primate genomes retain the remnants of an ancient A3 retrocopy: A3I. Furthermore, we found that some New World monkeys encode up to ten additional APOBEC3G (A3G) retrocopies. Some of these A3G retrocopies are transcribed in a variety of tissues and able to restrict retroviruses. Our findings suggest that host genomes co-opt retroelement activity in the germline to create new host restriction factors as another means to keep pace with the rapid evolution of viruses. (163)

scholarly journals Retroviruses drive the rapid evolution of mammalianAPOBEC3genes

2019 ◽  
Vol 117 (1) ◽  
pp. 610-618 ◽  
Author(s):  
Jumpei Ito ◽  
Robert J. Gifford ◽  
Kei Sato
Keyword(s):  
Gene Family ◽  
Fossil Record ◽  
Driving Force ◽  
Mammalian Species ◽  
Rapid Evolution ◽  
Endogenous Retroviruses ◽  
Mammalian Evolution ◽  
History Of ◽  
Mammalian Genomes

APOBEC3(A3) genes are members of theAID/APOBECgene family that are found exclusively in mammals.A3genes encode antiviral proteins that restrict the replication of retroviruses by inducing G-to-A mutations in their genomes and have undergone extensive amplification and diversification during mammalian evolution. Endogenous retroviruses (ERVs) are sequences derived from ancient retroviruses that are widespread mammalian genomes. In this study we characterize theA3repertoire and use the ERV fossil record to explore the long-term history of coevolutionary interaction between A3s and retroviruses. We examine the genomes of 160 mammalian species and identify 1,420AID/APOBEC-related genes, including representatives of previously uncharacterized lineages. We show thatA3genes have been amplified in mammals and that amplification is positively correlated with the extent of germline colonization by ERVs. Moreover, we demonstrate that the signatures of A3-mediated mutation can be detected in ERVs found throughout mammalian genomes and show that in mammalian species with expandedA3repertoires, ERVs are significantly enriched for G-to-A mutations. Finally, we show thatA3amplification occurred concurrently with prominent ERV invasions in primates. Our findings establish that conflict with retroviruses is a major driving force for the rapid evolution of mammalianA3genes.

scholarly journals Tracking interspecies transmission and long-term evolution of an ancient retrovirus using the genomes of modern mammals

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
William E Diehl ◽  
Nirali Patel ◽  
Kate Halm ◽  
Welkin E Johnson
Keyword(s):  
Fossil Record ◽  
Viral Infections ◽  
Endogenous Retroviruses ◽  
Interspecies Transmission ◽  
Viral Spread ◽  
Protein Functions ◽  
History Of ◽  
Mammalian Genomes ◽  
Retroviral Infections

Mammalian genomes typically contain hundreds of thousands of endogenous retroviruses (ERVs), derived from ancient retroviral infections. Using this molecular 'fossil' record, we reconstructed the natural history of a specific retrovirus lineage (ERV-Fc) that disseminated widely between ~33 and ~15 million years ago, corresponding to the Oligocene and early Miocene epochs. Intercontinental viral spread, numerous instances of interspecies transmission and emergence in hosts representing at least 11 mammalian orders, and a significant role for recombination in diversification of this viral lineage were also revealed. By reconstructing the canonical retroviral genes, we identified patterns of adaptation consistent with selection to maintain essential viral protein functions. Our results demonstrate the unique potential of the ERV fossil record for studying the processes of viral spread and emergence as they play out across macro-evolutionary timescales, such that looking back in time may prove insightful for predicting the long-term consequences of newly emerging viral infections.

scholarly journals Mobilization of Endogenous Retroviruses in Mice after Infection with an Exogenous Retrovirus

2008 ◽  
Vol 83 (6) ◽  
pp. 2429-2435 ◽  
Author(s):  
Leonard H. Evans ◽  
A. S. M. Alamgir ◽  
Nick Owens ◽  
Nick Weber ◽  
Kimmo Virtaneva ◽  
...  
Keyword(s):  
Germ Line ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Gene Sequences ◽  
Endogenous Viruses ◽  
Mammalian Genomes ◽  
Leukemia Viruses ◽  
Retroviral Infections ◽  
Ecotropic Virus ◽  
Rna Transcript

ABSTRACT Mammalian genomes harbor a large number of retroviral elements acquired as germ line insertions during evolution. Although many of the endogenous retroviruses are defective, several contain one or more intact viral genes that are expressed under certain physiological or pathological conditions. This is true of the endogenous polytropic retroviruses that generate recombinant polytropic murine leukemia viruses (MuLVs). In these recombinants the env gene sequences of exogenous ecotropic MuLVs are replaced with env gene sequences from an endogenous polytropic retrovirus. Although replication-competent endogenous polytropic retroviruses have not been observed, the recombinant polytropic viruses are capable of replicating in numerous species. Recombination occurs during reverse transcription of a virion RNA heterodimer comprised of an RNA transcript from an endogenous polytropic virus and an RNA transcript from an exogenous ecotropic MuLV RNA. It is possible that homodimers corresponding to two full-length endogenous RNA genomes are also packaged. Thus, infection by an exogenous virus may result not only in recombination with endogenous sequences, but also in the mobilization of complete endogenous retrovirus genomes via pseudotyping within exogenous retroviral virions. We report that the infection of mice with an ecotropic virus results in pseudotyping of intact endogenous viruses that have not undergone recombination. The endogenous retroviruses infect and are integrated into target cell genomes and subsequently replicate and spread as pseudotyped viruses. The mobilization of endogenous retroviruses upon infection with an exogenous retrovirus may represent a major interaction of exogenous retroviruses with endogenous retroviruses and may have profound effects on the pathogenicity of retroviral infections.

scholarly journals MysTR: an Endogenous Retrovirus Family in Mammals That Is Undergoing Recent Amplifications to Unprecedented Copy Numbers

2005 ◽  
Vol 79 (23) ◽  
pp. 14698-14707 ◽  
Author(s):  
Michael A. Cantrell ◽  
Martina M. Ederer ◽  
Issac K. Erickson ◽  
Vicki J. Swier ◽  
Robert J. Baker ◽  
...  
Keyword(s):  
Repetitive Sequences ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
South American ◽  
Coding Regions ◽  
Copy Numbers ◽  
Species Analysis ◽  
Outgroup Species ◽  
Mammalian Genomes ◽  
Oryzomys Palustris

ABSTRACT A large percentage of the repetitive elements in mammalian genomes are retroelements, which have been moved primarily by LINE-1 retrotransposons and endogenous retroviruses. Although LINE-1 elements have remained active throughout the mammalian radiation, specific groups of endogenous retroviruses generally remain active for comparatively shorter periods of time. Identification of an unusual extinction of LINE-1 activity in a group of South American rodents has opened a window for examination of the interplay in mammalian genomes between these ubiquitous retroelements. In the course of a search for any type of repetitive sequences whose copy numbers have substantially changed in Oryzomys palustris, a species that has lost LINE-1 activity, versus Sigmodon hispidus, a closely related species retaining LINE-1 activity, we have identified an endogenous retrovirus family differentially amplified in these two species. Analysis of three full-length, recently transposed copies, called mysTR elements, revealed gag, pro, and pol coding regions containing stop codons which may have accumulated either before or after retrotransposition. Isolation of related sequences in S. hispidus and the LINE-1 active outgroup species, Peromyscus maniculatus, by PCR of a pro-pol region has allowed determination of copy numbers in each species. Unusually high copy numbers of approximately 10,000 in O. palustris versus 1,000 in S. hispidus and 4,500 in the more distantly related P.maniculatus leave open the question of whether there is a connection between endogenous retrovirus activity and LINE-1 inactivity. Nevertheless, these independent expansions of mysTR represent recent amplifications of this endogenous retrovirus family to unprecedented levels.

scholarly journals Cause and Effectors: Whole-Genome Comparisons Reveal Shared but Rapidly Evolving Effector Sets among Host-Specific Plant-Castrating Fungi

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
William C. Beckerson ◽  
Ricardo C. Rodríguez de la Vega ◽  
Fanny E. Hartmann ◽  
Marine Duhamel ◽  
Tatiana Giraud ◽  
...  
Keyword(s):  
Positive Selection ◽  
Plant Pathogens ◽  
Pfam Domain ◽  
Rapid Evolution ◽  
Host Specialization ◽  
Secreted Proteins ◽  
Smut Fungi ◽  
Core Proteins ◽  
Genes Encoding ◽  
Species Specific

ABSTRACT Plant pathogens utilize a portfolio of secreted effectors to successfully infect and manipulate their hosts. It is, however, still unclear whether changes in secretomes leading to host specialization involve mostly effector gene gains/losses or changes in their sequences. To test these hypotheses, we compared the secretomes of three host-specific castrating anther smut fungi (Microbotryum), two being sister species. To address within-species evolution, which might involve coevolution and local adaptation, we compared the secretomes of strains from differentiated populations. We experimentally validated a subset of signal peptides. Secretomes ranged from 321 to 445 predicted secreted proteins (SPs), including a few species-specific proteins (42 to 75), and limited copy number variation, i.e., little gene family expansion or reduction. Between 52% and 68% of the SPs did not match any Pfam domain, a percentage that reached 80% for the small secreted proteins, indicating rapid evolution. In comparison to background genes, we indeed found SPs to be more differentiated among species and strains, more often under positive selection, and highly expressed in planta; repeat-induced point mutations (RIPs) had no role in effector diversification, as SPs were not closer to transposable elements than background genes and were not more RIP affected. Our study thus identified both conserved core proteins, likely required for the pathogenic life cycle of all Microbotryum species, and proteins that were species specific or evolving under positive selection; these proteins may be involved in host specialization and/or coevolution. Most changes among closely related host-specific pathogens, however, involved rapid changes in sequences rather than gene gains/losses. IMPORTANCE Plant pathogens use molecular weapons to successfully infect their hosts, secreting a large portfolio of various proteins and enzymes. Different plant species are often parasitized by host-specific pathogens; however, it is still unclear whether the molecular basis of such host specialization involves species-specific weapons or different variants of the same weapons. We therefore compared the genes encoding secreted proteins in three plant-castrating pathogens parasitizing different host plants, producing their spores in plant anthers by replacing pollen. We validated our predictions for secretion signals for some genes and checked that our predicted secreted proteins were often highly expressed during plant infection. While we found few species-specific secreted proteins, numerous genes encoding secreted proteins showed signs of rapid evolution and of natural selection. Our study thus found that most changes among closely related host-specific pathogens involved rapid adaptive changes in shared molecular weapons rather than innovations for new weapons.

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