Escalation of genome defense capacity enables control of an expanding meiotic driver

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(2)

Published: Jan. 7, 2025

From RNA interference to chromatin silencing, diverse genome defense pathways silence selfish genetic elements safeguard integrity. Despite their diversity, different share a modular organization, where numerous specificity factors identify targets and common effectors them. In the PIWI-interacting (piRNA) pathway, target RNAs are first identified by complementary base pairing with piRNAs then silenced PIWI-clade nucleases. Such binary architecture allows systems be readily adaptable, new can captured via innovation of factors. Thus, our current understanding against lineage-specific genes has been largely limited factor innovations, while it remains poorly understood whether other types innovations required. Here, we describe type innovation, which escalates capacity control recently expanded gene in Drosophila melanogaster . Through targeted RNAi screen for repressors Stellate —a evolved meiotic driver—we factor, Trailblazer. Trailblazer is transcription that promotes expression two nucleases, Aub AGO3, match abundance. Recent DNA-binding domain enabled elevate AGO3 expression, thereby escalating silencing piRNA pathway tame fertility. As copy-number expansion recurrent feature across tree life, envision augmenting quantitatively repeatedly employed strategy evolution.

Language: Английский

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The Drosophila ZAD zinc finger protein Kipferl guides Rhino to piRNA clusters

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Oct. 4, 2022

RNA interference systems depend on the synthesis of small precursors whose sequences define target spectrum these silencing pathways. The Drosophila Heterochromatin Protein 1 (HP1) variant Rhino permits transcription PIWI-interacting (piRNA) within transposon-rich heterochromatic loci in germline cells. Current models propose that Rhino’s specific chromatin occupancy at piRNA source is determined by histone marks and maternally inherited piRNAs, but also imply existence other, undiscovered specificity cues. Here, we identify a member diverse family zinc finger associated domain (ZAD)-C 2 H proteins, Kipferl, as critical cofactor ovaries. By binding to guanosine-rich DNA motifs interacting with chromodomain, Kipferl recruits stabilizes it chromatin. In kipferl mutant flies, lost from most its instead accumulates pericentromeric Satellite arrays, resulting decreased levels transposon targeting piRNAs impaired fertility. Our findings reveal sequence, addition H3K9me3 mark, determines identity provide insight into how might be caught crossfire genetic conflicts.

Language: Английский

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Expansion and loss of sperm nuclear basic protein genes in Drosophila correspond with genetic conflicts between sex chromosomes

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Feb. 10, 2023

Many animal species employ sperm nuclear basic proteins (SNBPs) or protamines to package genomes tightly. SNBPs vary across lineages and evolve rapidly in mammals. We used a phylogenomic approach investigate SNBP diversification Drosophila species. found that most genes melanogaster under positive selection except for essential male fertility. Unexpectedly, evolutionarily young are more likely be critical fertility than ancient, conserved genes. For example, CG30056 is dispensable despite being one of three universally retained 19 independent gene amplification events occurred preferentially on sex chromosomes. Conversely, the montium group lost otherwise-conserved genes, coincident with an X-Y chromosomal fusion. Furthermore, became linked chromosomes via fusions were degenerate relocate back autosomes. hypothesize autosomal suppress meiotic drive, whereas sex-chromosomal expansions lead drive. render by making X-versus-Y drive obsolete costly. Thus, genetic conflicts between may rapid evolution during spermatogenesis

Language: Английский

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Transposable elements drive the evolution of metazoan zinc finger genes

Genome Research, Journal Year: 2023, Volume and Issue: 33(8), P. 1325 - 1339

Published: Aug. 1, 2023

Cys2-His2 zinc finger genes (ZNFs) form the largest family of transcription factors in metazoans. ZNF evolution is highly dynamic and characterized by rapid expansion contraction numerous subfamilies across animal phylogeny. The forces mechanisms underlying remain poorly understood, but there growing evidence that, tetrapods, targeting repression lineage-specific transposable elements (TEs) plays a critical role Krüppel-associated box (KZNF) subfamily. Currently, it unknown whether this function coevolutionary relationship unique to KZNFs or broader feature metazoan ZNFs. Here, we present that genomic conflict with TEs has been central driver diversification ZNFs animals. Sampling from 3221 genome assemblies, show copy number retroelements correlates at least 750 million years evolution. Using computational predictions, preferentially bind diverse species. We further investigate subfamily found cyprinid fish, which conserved sequence dubbed fish N-terminal finger–associated (FiNZ) domain. Zebrafish possess approximately 700 FiNZ-ZNFs, many are evolving adaptively under positive selection. Like mammalian KZNFs, most zebrafish FiNZ-ZNFs expressed onset zygotic activation, blocking their translation using morpholinos during early embryogenesis results derepression transcriptionally active TEs. Together, these data suggest intimately connected TE throughout

Language: Английский

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Functional innovation through new genes as a general evolutionary process

Nature Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Language: Английский

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Causes and Consequences of Varying Transposable Element Activity: An Evolutionary Perspective

Annual Review of Genomics and Human Genetics, Journal Year: 2024, Volume and Issue: 25(1), P. 1 - 25

Published: April 11, 2024

Transposable elements (TEs) are genomic parasites found in nearly all eukaryotes, including humans. This evolutionary success of TEs is due to their replicative activity, involving insertion into new locations. TE activity varies at multiple levels, from between taxa within individuals. The rapidly accumulating evidence the influence on human health, as well rapid growth tools study it, motivated an evaluation what we know about thus far. Here, discuss why varies, and consequences this variation, perspective. By studying nonhuman organisms context theories, can shed light factors that affect activity. While usually deleterious, some have lasting impacts by conferring benefits host or affecting other processes.

Language: Английский

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

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Nov. 10, 2020

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

Language: Английский

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Genome-wide analysis of pseudogenes reveals HBBP1’s human-specific essentiality in erythropoiesis and implication in β-thalassemia

Developmental Cell, Journal Year: 2021, Volume and Issue: 56(4), P. 478 - 493.e11

Published: Jan. 20, 2021

Language: Английский

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Establishment of H3K9me3-dependent heterochromatin during embryogenesis in Drosophila miranda

eLife, Journal Year: 2021, Volume and Issue: 10

Published: June 15, 2021

Heterochromatin is a key architectural feature of eukaryotic genomes crucial for silencing repetitive elements. During Drosophila embryonic cellularization, heterochromatin rapidly appears over sequences, but the molecular details how established are poorly understood. Here, we map genome-wide distribution H3K9me3-dependent in individual embryos miranda at precisely staged developmental time points. We find that canonical H3K9me3 enrichment prior to cellularization and matures into stable broad domains through development. Intriguingly, initial nucleation sites appear as early stage 3 transposable elements (TEs) progressively broaden, consistent with spreading neighboring nucleosomes. The earliest limited specific regions small number recently active retrotransposon families often promoter 5’ LTR retrotransposons, while late develop broadly across entirety most TEs. Interestingly, nucleating TEs strongly associated abundant maternal piRNAs show zygotic transcription. These results support model piRNA-associated co-transcriptional also suggesting additional mechanisms site-restricted pre-cellular embryos.

Language: Английский

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Genomic analyses of new genes and their phenotypic effects reveal rapid evolution of essential functions in Drosophila development

PLoS Genetics, Journal Year: 2021, Volume and Issue: 17(7), P. e1009654 - e1009654

Published: July 9, 2021

It is a conventionally held dogma that the genetic basis underlying development conserved in long evolutionary time scale. Ample experiments based on mutational, biochemical, functional, and complementary knockdown/knockout approaches have revealed unexpectedly important role of recently evolved new genes Drosophila. The recent progress genome-wide experimental testing gene effects improvements computational identification (< 40 million years ago, Mya) open door to investigate evolution essentiality with phylogenetically high resolution. These advancements also raised interesting issues techniques concepts related phenotypic effect analyses genes, particularly those originated. Here we reported our these issues, including reproducibility efficiency knockdown experiment difference between RNAi libraries effects. We further analyzed large data from knockdowns 11,354 (~75% Drosophila melanogaster total genes), 702 (~66% species aged < Mya), revealing similarly proportion (~32.2%) essential originated various Sophophora subgenus lineages distant ancestors beyond genus. transcriptional compensation CRISPR knockout were detected for highly similar duplicate copies. Knockout few young analogous functions development. Taken together, provide valuable detection general strong evidence concept quickly viability during

Language: Английский

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