Meiotic drive mechanisms: lessons from
            Drosophila

Meiotic drivers are selfish genetic elements that bias their transmission into gametes, often to the detriment of the rest of the genome. The resulting intragenomic conflicts triggered by meiotic drive create evolutionary arms races and shape genome evolution. The phenomenon of meiotic drive is widespread across taxa but is particularly prominent in the Drosophila genus. Recent studies in Drosophila have provided insights into the genetic origins of drivers and their molecular mechanisms. Here, we review the current literature on mechanisms of drive with an emphasis on sperm killers in Drosophila species. In these systems, meiotic drivers often evolve from gene duplications and targets are generally linked to heterochromatin. While dense in repetitive elements and difficult to study using traditional genetic and genomic approaches, recent work in Drosophila has made progress on the heterochromatic compartment of the genome. Although we still understand little about precise drive mechanisms, studies of male drive systems are converging on common themes such as heterochromatin regulation, small RNA pathways, and nuclear transport pathways. Meiotic drive systems are therefore promising models for discovering fundamental features of gametogenesis.

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Red queen's race: rapid evolutionary dynamics of an expanding family of meiotic drive factors and their hpRNA suppressors

10.1101/2021.08.05.454923 ◽

2021 ◽

Author(s):

Jeffrey Vedanayagam ◽

Ching-Jung Lin ◽

Eric C. Lai

Keyword(s):

Evolutionary Dynamics ◽

Sex Chromosome ◽

De Novo ◽

Independent Set ◽

Meiotic Drive ◽

Sperm Chromatin ◽

Arms Races ◽

X Chromosomes ◽

Selfish Genetic Elements ◽

Satellite Repeats

Meiotic drivers are a class of selfish genetic elements that are widespread across eukaryotes. Their activities are often detrimental to organismal fitness and thus trigger drive suppression to ensure fair segregation during meiosis. Accordingly, their existence is frequently hidden in genomes, and their molecular functions are little known. Here, we trace evolutionary steps that generated the Dox meiotic drive system in Drosophila simulans (Dsim), which distorts male:female balance (sex-ratio) by depleting male progeny. We show that Dox emerged via stepwise mobilization and acquisition of portions of multiple D. melanogaster genes, including the sperm chromatin packaging gene protamine. Moreover, we reveal novel Dox homologs in Dsim and massive, recent, amplification of Dox superfamily genes specifically on X chromosomes of its closest sister species D. mauritiana (Dmau) and D. sechellia (Dsech). The emergence of Dox superfamily genes is tightly associated with 1.688 family satellite repeats that flank de novo genomic copies. In concert, we find coordinated emergence and diversification of autosomal hairpin RNA/siRNAs loci that target subsets of Dox superfamily genes across simulans clade species. Finally, an independent set of protamine amplifications the Y chromosome of D. melanogaster indicates that protamine genes are frequent and recurrent players in sex chromosome dynamics. Overall, we reveal fierce genetic arms races between meiotic drive factors and siRNA suppressors associated with recent speciation.

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Protease-mediated processing of Argonaute proteins controls small RNA association

10.1101/2020.12.09.417253 ◽

2020 ◽

Author(s):

Rajani Kanth Gudipati ◽

Kathrin Braun ◽

Foivos Gypas ◽

Daniel Hess ◽

Jan Schreier ◽

...

Keyword(s):

Small Rna ◽

Small Rnas ◽

Proteolytic Processing ◽

Genome Integrity ◽

Wild Type ◽

Selfish Genetic Elements ◽

Argonaute Proteins ◽

Processing Activity ◽

Rna Pathways

SummarySmall RNA pathways defend the germlines of animals against selfish genetic elements and help to maintain genomic integrity. At the same time, their activity needs to be well-controlled to prevent silencing of ‘self’ genes. Here, we reveal a proteolytic mechanism that controls endogenous small interfering (22G) RNA activity in the Caenorhabditis elegans germline to protect genome integrity and maintain fertility. We find that WAGO-1 and WAGO-3 Argonaute (Ago) proteins are matured through proteolytic processing of their unusually proline-rich N-termini. In the absence of DPF-3, a P-granule-localized N-terminal dipeptidase orthologous to mammalian DPP8/9, processing fails, causing a change of identity of 22G RNAs bound to these WAGO proteins. Desilencing of repeat- and transposon-derived transcripts, DNA damage and acute sterility ensue. These phenotypes are recapitulated when WAGO-1 and WAGO-3 are rendered resistant to DFP-3-mediated processing, identifying them as critical substrates of DPF-3. We conclude that N-terminal processing of Ago proteins regulates their activity and promotes discrimination of self from non-self by ensuring association with the proper complement of small RNAs.Graphical Abstract: The role of DPF-3 in the fertility of the animalsIn wild type animals, the WAGO-1 and WAGO-3 Argonaute proteins are produced as immature pro-proteins with N-termini (N) that are unusually rich in prolines (P). N-terminal processing by DPF-3 is required for loading of the proper small RNA cargo and stabilization of WAGO-3. Accordingly, loss of this processing activity causes desilencing of transposable elements (TE), cell death and sterility.

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Nuclear transport genes recurrently duplicate by means of RNA intermediates in Drosophila but not in other insects

BMC Genomics ◽

10.1186/s12864-021-08170-4 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ayda Mirsalehi ◽

Dragomira N. Markova ◽

Mohammadmehdi Eslamieh ◽

Esther Betrán

Keyword(s):

Gene Evolution ◽

Nuclear Transport ◽

Meiotic Drive ◽

Gene Duplications ◽

Selective Pressures ◽

Drive Systems ◽

Underlying Mechanisms ◽

Male Specific ◽

Phylogenomic Study ◽

Dipteran Species

Abstract Background The nuclear transport machinery is involved in a well-known male meiotic drive system in Drosophila. Fast gene evolution and gene duplications have been major underlying mechanisms in the evolution of meiotic drive systems, and this might include some nuclear transport genes in Drosophila. So, using a comprehensive, detailed phylogenomic study, we examined 51 insect genomes for the duplication of the same nuclear transport genes. Results We find that most of the nuclear transport duplications in Drosophila are of a few classes of nuclear transport genes, RNA mediated and fast evolving. We also retrieve many pseudogenes for the Ran gene. Some of the duplicates are relatively young and likely contributing to the turnover expected for genes under strong but changing selective pressures. These duplications are potentially revealing what features of nuclear transport are under selection. Unlike in flies, we find only a few duplications when we study the Drosophila duplicated nuclear transport genes in dipteran species outside of Drosophila, and none in other insects. Conclusions These findings strengthen the hypothesis that nuclear transport gene duplicates in Drosophila evolve either as drivers or suppressors of meiotic drive systems or as other male-specific adaptations circumscribed to flies and involving a handful of nuclear transport functions.

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P-bodies and the miRNA pathway regulate translational repression of bicoid mRNA during Drosophila melanogaster oogenesis

10.1101/283630 ◽

2018 ◽

Author(s):

John M. McLaughlin ◽

Daniel F.Q. Smith ◽

Irina E. Catrina ◽

Diana P. Bratu

Keyword(s):

Drosophila Melanogaster ◽

Small Rna ◽

Translational Regulation ◽

Translational Repression ◽

Temporal Regulation ◽

P Bodies ◽

Maternal Transcripts ◽

Spatio Temporal ◽

Mirna Pathway ◽

Rna Pathways

ABSTRACTEmbryonic axis patterning in Drosophila melanogaster is partly achieved by mRNAs that are maternally localized to the oocyte; the spatio-temporal regulation of these transcripts’ stability and translation is a characteristic feature of oogenesis. While protein regulatory factors are necessary for the translational regulation of some maternal transcripts (e.g. oskar and gurken), small RNA pathways are also known to regulate mRNA stability and translation in eukaryotes. MicroRNAs (miRNAs) are small RNA regulators of gene expression, widely conserved throughout eukaryotic genomes and essential for animal development. The main D. melanogaster anterior determinant, bicoid, is maternally transcribed, but it is not translated until early embryogenesis. We investigated the possibility that its translational repression during oogenesis is mediated by miRNA activity. We found that the bicoid 3’UTR contains a highly conserved, predicted binding site for miR-305. Our studies reveal that miR-305 regulates the translation of a reporter gene containing the bicoid 3’UTR in cell culture, and that miR-305 only partially contributes to bicoid mRNA translational repression during oogenesis. We also found that Processing bodies (P-bodies) in the egg chamber may play a role in stabilizing bicoid and other maternal transcripts. Here, we offer insights into the possible role of P-bodies and the miRNA pathway in the translational repression of bicoid mRNA during oogenesis.

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MULTIPLE MEIOTIC DRIVE SYSTEMS IN THE DROSOPHILA MELANOGASTER MALE

Genetics ◽

10.1093/genetics/72.1.105 ◽

1972 ◽

Vol 72 (1) ◽

pp. 105-115

Author(s):

George L Gabor Miklos ◽

Armon F Yanders ◽

W J Peacock

Keyword(s):

Drosophila Melanogaster ◽

Survival Probability ◽

Sex Chromosome ◽

Meiotic Drive ◽

The Other ◽

Segregation Distorter ◽

Two Systems ◽

Combined Action ◽

Drive Systems

ABSTRACT The behaviour of two "meiotic drive" systems, Segregation-Distorter (SD) and the sex chromosome sc4sc8 has been examined in the same meiocyte. It has been found that the two systems interact in a specific way. When the distorting effects of SD and sc4sc8 are against each other, there is no detectable interaction. Each system is apparently oblivious to the presence of the other, gametes being produced according to independence expectations. However when the affected chromosomes are at the same meiotic pole an interaction occurs; the survival probability of the gamete containing both distorted chromosomal products is increased, rather than being decreased by the combined action of two systems.

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Signal Peptide-Dependent Protein Transport inBacillus subtilis: a Genome-Based Survey of the Secretome

Microbiology and Molecular Biology Reviews ◽

10.1128/mmbr.64.3.515-547.2000 ◽

2000 ◽

Vol 64 (3) ◽

pp. 515-547 ◽

Cited By ~ 522

Author(s):

Harold Tjalsma ◽

Albert Bolhuis ◽

Jan D. H. Jongbloed ◽

Sierd Bron ◽

Jan Maarten van Dijl

Keyword(s):

Protein Secretion ◽

Molecular Mechanisms ◽

Protein Transport ◽

Transport Systems ◽

Future Research ◽

Yeast Saccharomyces Cerevisiae ◽

Transport Pathways ◽

Amino Terminal ◽

Cell Factories ◽

A Genome

SUMMARY One of the most salient features of Bacillus subtilis and related bacilli is their natural capacity to secrete a variety of proteins into their environment, frequently to high concentrations. This has led to the commercial exploitation of bacilli as major “cell factories” for secreted enzymes. The recent sequencing of the genome of B. subtilis has provided major new impulse for analysis of the molecular mechanisms underlying protein secretion by this organism. Most importantly, the genome sequence has allowed predictions about the composition of the secretome, which includes both the pathways for protein transport and the secreted proteins. The present survey of the secretome describes four distinct pathways for protein export from the cytoplasm and approximately 300 proteins with the potential to be exported. By far the largest number of exported proteins are predicted to follow the major “Sec” pathway for protein secretion. In contrast, the twin-arginine translocation “Tat” pathway, a type IV prepilin-like export pathway for competence development, and ATP-binding cassette transporters can be regarded as “special-purpose” pathways, through which only a few proteins are transported. The properties of distinct classes of amino-terminal signal peptides, directing proteins into the various protein transport pathways, as well as the major components of each pathway are discussed. The predictions and comparisons in this review pinpoint important differences as well as similarities between protein transport systems in B. subtilis and other well-studied organisms, such as Escherichia coli and the yeast Saccharomyces cerevisiae. Thus, they may serve as a lead for future research and applications.

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tRNA 2′-O-methylation by a duo of TRM7/FTSJ1 proteins modulates small RNA silencing in Drosophila

Nucleic Acids Research ◽

10.1093/nar/gkaa002 ◽

2020 ◽

Vol 48 (4) ◽

pp. 2050-2072 ◽

Cited By ~ 4

Author(s):

Margarita T Angelova ◽

Dilyana G Dimitrova ◽

Bruno Da Silva ◽

Virginie Marchand ◽

Caroline Jacquier ◽

...

Keyword(s):

Small Rna ◽

Rna Structure ◽

Rna Silencing ◽

Defense Mechanisms ◽

Rna Virus ◽

Virus Infections ◽

Self Recognition ◽

Silencing Pathways ◽

Rna Pathways ◽

And Function

Abstract 2′-O-Methylation (Nm) represents one of the most common RNA modifications. Nm affects RNA structure and function with crucial roles in various RNA-mediated processes ranging from RNA silencing, translation, self versus non-self recognition to viral defense mechanisms. Here, we identify two Nm methyltransferases (Nm-MTases) in Drosophila melanogaster (CG7009 and CG5220) as functional orthologs of yeast TRM7 and human FTSJ1. Genetic knockout studies together with MALDI-TOF mass spectrometry and RiboMethSeq mapping revealed that CG7009 is responsible for methylating the wobble position in tRNAPhe, tRNATrp and tRNALeu, while CG5220 methylates position C32 in the same tRNAs and also targets additional tRNAs. CG7009 or CG5220 mutant animals were viable and fertile but exhibited various phenotypes such as lifespan reduction, small RNA pathways dysfunction and increased sensitivity to RNA virus infections. Our results provide the first detailed characterization of two TRM7 family members in Drosophila and uncover a molecular link between enzymes catalyzing Nm at specific tRNAs and small RNA-induced gene silencing pathways.

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Specialization and evolution of endogenous small RNA pathways

Nature Reviews Genetics ◽

10.1038/nrg2179 ◽

2007 ◽

Vol 8 (11) ◽

pp. 884-896 ◽

Cited By ~ 459

Author(s):

Elisabeth J. Chapman ◽

James C. Carrington

Keyword(s):

Small Rna ◽

Rna Pathways

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Double trouble: combined action of meiotic drive and Wolbachia feminization in Eurema butterflies

Biology Letters ◽

10.1098/rsbl.2015.0095 ◽

2015 ◽

Vol 11 (5) ◽

pp. 20150095 ◽

Cited By ~ 27

Author(s):

Peter Kern ◽

James M. Cook ◽

Daisuke Kageyama ◽

Markus Riegler

Keyword(s):

Meiotic Drive ◽

Sex Bias ◽

Z Chromosome ◽

Female Development ◽

Pcr Assay ◽

Interphase Nuclei ◽

Diverse Range ◽

Selfish Genetic Elements ◽

Combined Action ◽

Quantitative Pcr Assay

Arthropod sex ratios can be manipulated by a diverse range of selfish genetic elements, including maternally inherited Wolbachia bacteria. Feminization by Wolbachia is rare but has been described for Eurema mandarina butterflies . In this species, some phenotypic and functional females, thought to be ZZ genetic males, are infected with a feminizing Wolbachia strain, w Fem. Meanwhile, heterogametic WZ females are not infected with w Fem. Here, we establish a quantitative PCR assay allowing reliable sexing in three Eurema species. Against expectation, all E. mandarina females, including w Fem females, had only one Z chromosome that was paternally inherited. Observation of somatic interphase nuclei confirmed that W chromatin was absent in w Fem females, but present in females without w Fem. We conclude that the sex bias in w Fem lines is due to meiotic drive (MD) that excludes the maternal Z and thus prevents formation of ZZ males. Furthermore, w Fem lines may have lost the W chromosome or harbour a dysfunctional version, yet rely on w Fem for female development; removal of w Fem results in all-male offspring. This is the first study that demonstrates an interaction between MD and Wolbachia feminization, and it highlights endosymbionts as potentially confounding factors in MD of sex chromosomes.

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