2019 Jan 31
Rapid Evolution and Conserved Function of the piRNA Pathway
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Rapid Evolution and Conserved Function of the piRNA Pathway
Transposons are major genome constituents that can mobilize and trigger mutations, DNA breaks and chromosome rearrangements. Transposon silencing is particularly important in the germline, which is dedicated to transmission of the inherited genome. Piwi-interacting RNAs (piRNAs) guide a host defence system that transcriptionally and post-transcriptionally silences transposons during germline development. While germline control of transposons by the piRNA pathway is conserved, many piRNA pathway genes are evolving rapidly under positive selection, and the piRNA biogenesis machinery shows remarkable phylogenetic diversity. Conservation of core function combined with rapid gene evolution is characteristic of a host-pathogen arms race, suggesting that transposons and the piRNA pathway are engaged in an evolutionary tug of war that is driving divergence of the biogenesis machinery. Recent studies suggest that this process may produce biochemical incompatibilities that contribute to reproductive isolation and species divergence.
adaptive evolution; host–pathogen arms race; pathogen mimicry; piRNA; transposon regulation.
Conflict of interest statement
We declare that we have no competing interests.
Summary of transposition mechanisms. Transposition mechanisms for major eukaryotic transposons. (
a, b) DNA transposons which transpose through a DNA intermediate. ( c, d) RNA or retrotransposons which transpose through an RNA intermediate. Target and donor sites are shown in black and grey, respectively. Old and new transposable elements (TEs) are shown in red and green, respectively. Examples of such transposons are denoted. ( a) DNA transposons, such as P-elements, excise from the donor and insert into a new site. ( b) Helitrons transfer one DNA strand from the donor to the recipient site. The donor site synthesizes a new strand (shown in blue). The recipient site also synthesizes a new strand. ( c) LTR retrotransposons transcribe into an RNA. This RNA is reverse-transcribed and inserted into a new site. ( d) Non-LTR retrotransposons also transcribe into an RNA. The RNA is reverse-transcribed at the insertion site. Thus, the original donor site is unaffected for retrotransposons.
Organization of piRNA clusters and possible conflicts with transposons. (
a) Genome browser view of 42AB piRNA cluster in D. melanogaster showing transposon organization within the cluster and piRNA levels in wild type and rhino mutant ovaries. ( b) Cluster conflicts with transposons. When a transposon jumps into a new species, it can transpose fast and make multiple copies. Once the new transposon jumps into a cluster, piRNAs are generated against the new transposon and these piRNAs can silence the new TE. Thus, it is advantageous for clusters to incorporate new TEs but is deleterious for the transposons.
piRNA biogenesis mechanisms in flies, mice and worms. Simplified models for piRNA biogenesis are shown for
D. melanogaster (flies), M. musculus (mice) and C. elegans (worms). ( a) Transcription at piRNA clusters, ( b) the piRNA biogenesis process and ( c) transposon silencing by piRNAs. In the fly germline, piRNA clusters are marked by H3K9me3. The transcription by RNA Pol II is facilitated by RDC complex along with Moonshiner and TRF2. The transcripts are bound by TREX and UAP56. In the cytoplasm, these transcripts are processed into piRNAs by a ping-pong amplification cycle. The phased piRNAs are further bound by Piwi which can lead to transcriptional silencing by directing histone modification. In the soma, piRNA clusters are transcribed by canonical promoter by RNA Pol II. These transcripts are processed into piRNAs in the Yb bodies present in the cytoplasm and loaded into Piwi, which enters the nucleus to silence transposons. The Slicer cleavage by PIWI Argonautes is shown by vertical scissors and Zucchini mediated cleavage leading to phased piRNAs is shown by tilted scissors. In mice, A-MYB acts as a transcription factor for pachytene piRNA cluster transcription by RNA Pol II. No such transcription factor is known for pre-pachytene piRNA clusters. The ping-pong cycle in the pre-pachytene stage leads to an amplification of piRNAs. piRNA bound MIWI2 can silence transposons by directing DNA methylation. In the pachytene stage, MIWI Slicer cleavage leads to post-transcriptional silencing of transposons. In worms, each piRNA cluster encodes for one piRNA and has its own promoter identified by the Ruby motif. The RNA Pol II mediated transcription is directed by Forkhead and TOFU proteins. Recognition of target by piRNA bound PRG-1 leads to a generation of 22G-RNAs. These secondary 22G-RNAs can mediate transcriptional silencing when in complex with worm specific Argonautes (WAGOs).
A model for piRNA pathway evolution by transposon-encoded mimics. (
a) In Drosophila, Rhino (Rhi) and Deadlock (Del) interact and bind to piRNA clusters, promoting transcription and piRNA processing, and the Rhi–Del interface is rapidly evolving. We speculate that the evolution of this interface was driven by a transposon-encoded protein that mimics the Rhi-binding surface of Del. Step 1. The mimic (M) competes for Rhi, inhibiting biogenesis. Step 2. Selection acts on Rhi mutations that reduce mimic binding, increasing Rhi–Del interactions, but at a cost of reduced affinity. Step 3. Del mutations then restore full Rhi binding. ( b) Speculative model for coupled evolution of the RDC complex. Rhi (R) binds to Del (D), and the Rhi–Del complex recruits Cutoff (Cuff, C) to form the RDC. A mimic that competes for productive Rhi–Del binding would shift the equilibrium to the left, reducing RDC levels, compromising piRNA production. RDC levels could be restored by Rhi mutations, as in ( a), or by Cuff mutations that enhance binding to the Rhi–Del complex. In this model, a mimic targeting a single interaction within a coupled system could lead to a cascade of compensatory mutations, altering binding between other proteins in the complex.
Transposon variation can drive reproductive isolation. Hypothetical scenario for crosses between populations A and B having unique transposons. Population A has transposon
α, but not β and population B has transposon β, but not α. Crosses between populations lead to an activation of transposons coming from the father due to the absence of maternal piRNAs against TE unique to father and sterility. This would establish reproductive barriers and lead to a speciation event.
Adaptive Evolution Leads to Cross-Species Incompatibility in the piRNA Transposon Silencing Machinery
SS Parhad et al.
Dev Cell 43 (1), 60-70.e5.
Reproductive isolation defines species divergence and is linked to adaptive evolution of hybrid incompatibility genes. Hybrids between Drosophila melanogaster and Drosoph …
Analysis of Hydra PIWI Proteins and piRNAs Uncover Early Evolutionary Origins of the piRNA Pathway
RS Lim et al.
Dev Biol 386 (1), 237-51.
To preserve genome integrity, an evolutionarily conserved small RNA-based silencing mechanism involving PIWI proteins and PIWI-interacting RNAs (piRNAs) represses potenti …
Rapid Evolution of piRNA Pathway in the Teleost Fish: Implication for an Adaptation to Transposon Diversity
M Yi et al.
Genome Biol Evol 6 (6), 1393-407.
The Piwi-interacting RNA (piRNA) pathway is responsible for germline specification, gametogenesis, transposon silencing, and genome integrity. Transposable elements can d …
Two Distinct Transcriptional Controls Triggered by Nuclear Piwi-piRISCs in the Drosophila piRNA Pathway
K Sato et al.
Curr Opin Struct Biol 53, 69-76.
Transposons occupy a large proportion of eukaryotic genomes. Spontaneous movement of transposons within the genome leads to genomic mutations that are often life threaten …
Biology of PIWI-interacting RNAs: New Insights Into Biogenesis and Function Inside and Outside of Germlines
H Ishizu et al.
Genes Dev 26 (21), 2361-73.
PIWI-interacting RNAs (piRNAs) are endogenous small noncoding RNAs that act as guardians of the genome, protecting it from invasive transposable elements in the germline. …
PubMed Central articles
PIWI Proteins and piRNAs in the Nervous System
Mol Cells 42 (12), 828-835.
PIWI Argonaute proteins and Piwi-interacting RNAs (piRNAs) are expressed in all animal species and play a critical role in cellular defense by inhibiting the activation o …
Assembly and Function of Gonad-Specific Non-Membranous Organelles in
Drosophila piRNA Biogenesis
S Hirakata et al.
Noncoding RNA 5 (4).
PIWI-interacting RNAs (piRNAs) are small non-coding RNAs that repress transposons in animal germlines. This protects the genome from the invasive DNA elements. piRNA path …
The piRNA Response to Retroviral Invasion of the Koala Genome
T Yu et al.
Cell 179 (3), 632-643.e12.
Antisense Piwi-interacting RNAs (piRNAs) guide silencing of established transposons during germline development, and sense piRNAs drive ping-pong amplification of the ant …
Host-transposon Interactions: Conflict, Cooperation, and Cooption
RL Cosby et al.
Genes Dev 33 (17-18), 1098-1116.
Transposable elements (TEs) are mobile DNA sequences that colonize genomes and threaten genome integrity. As a result, several mechanisms appear to have emerged during eu …
Alberts B. 2017. Molecular biology of the cell. Boca Raton, FL: CRC Press.
Daugherty MD, Malik HS. 2012. Rules of engagement: molecular insights from host-virus arms races. Annu. Rev. Genet. 46, 677–700. (10.1146/annurev-genet-110711-155522)
Van Valen LM. 1973. A new evolutionary law. Evol. Theory 1, 1–30.
Khurana JS, Theurkauf W. 2010. piRNAs, transposon silencing, and Drosophila germline development. J. Cell Biol. 191, 905–913. (10.1083/jcb.201006034)
Ayarpadikannan S, Kim HS. 2014. The impact of transposable elements in genome evolution and genetic instability and their implications in various diseases. Genomics Inform. 12, 98–104. (10.5808/GI.2014.12.3.98)
Research Support, N.I.H., Extramural