Taming active transposons at Drosophila telomeres: The interconnection between HipHop’s roles in capping and transcriptional silencing

Drosophila chromosomes are elongated by retrotransposon attachment, a process poorly understood. Here we characterized a mutation affecting the HipHop telomere-capping protein. In mutant ovaries and the embryos that they produce, telomere retrotransposons are activated and transposon RNP accumulates. Genetic results are consistent with that this hiphop mutation weakens the efficacy of HP1-mediated silencing while leaving piRNA-based mechanisms largely intact. Remarkably, mutant females display normal fecundity suggesting that telomere de-silencing is compatible with germline development. Moreover, unlike prior mutants with overactive telomeres, the hiphop stock does not over-accumulate transposons for hundreds of generations. This is likely due to the loss of HipHop’s abilities both to silence transcription and to recruit transposons to telomeres in the mutant. Furthermore, embryos produced by mutant mothers experience a checkpoint activation, and a further loss of maternal HipHop leads to end-to-end fusion and embryonic arrest. Telomeric retroelements fulfill an essential function yet maintain a potentially conflicting relationship with their Drosophila host. Our study thus showcases a possible intermediate in this arm race in which the host is adapting to over-activated transposons while maintaining genome stability. Our results suggest that the collapse of such a relationship might only occur when the selfish element acquires the ability to target non-telomeric regions of the genome. HipHop is likely part of this machinery restricting the elements to the gene-poor region of telomeres. Lastly, our hiphop mutation behaves as a recessive suppressor of PEV that is mediated by centric heterochromatin, suggesting its broader effect on chromatin not limited to telomeres.

The ‘Selfish Element’: How Sperm and Egg Donors Construct Plausibly Moral Accounts of the Decision to Donate

Multiple sociological studies have demonstrated how talk of ‘good’ motives enables people to maintain the presentation of a moral self in the context of stigmatised behaviours. Far fewer have examined why people sometimes describe acting for the ‘wrong reasons’ or choose to qualify, or reject, assumptions that they are motivated by a desire to ‘do good’. In this article, I analyse one such situation: sperm donors who describe being partially motivated by a ‘selfish’ desire to procreate, a motive which these same men frame as morally questionable. I argue that such accounts are explicable if we consider the (gendered) interactional and cultural contexts in which they are produced, particularly the way interactive contexts shape the desirability and achievability of plausibility and authenticity. I suggest that analysis of similar social phenomena can support sociologists in better understanding the complex ways in which moral practices are woven into social interactions.

A functional bacteria-derived restriction modification system in the mitochondrion of a heterotrophic protist

The overarching trend in mitochondrial genome evolution is functional streamlining coupled with gene loss; therefore, gene acquisition by mitochondria is considered to be exceedingly rare. Selfish elements in the form of self-splicing introns occur in many organellar genomes, but the wider diversity of selfish elements, and how they persist in the DNA of organelles, has not been explored. In the mitochondrial genome of a marine heterotrophic katablepharid protist, we identify a functional type II restriction modification (RM) system originating from a horizontal gene transfer (HGT) event involving bacteria related to flavobacteria. This RM system consists of an HpaII-like endonuclease and a cognate cytosine methyltransferase (CM). We demonstrate that these proteins are functional by heterologous expression in both bacterial and eukaryotic cells. These results suggest that a mitochondrial-encoded RM system can function as a toxin–antitoxin selfish element and that such elements could be co-opted by eukaryotic genomes to drive biased organellar inheritance.

The Enterprise: A massive transposon carrying Spok meiotic drive genes

The genomes of eukaryotes are full of parasitic sequences known as transposable elements (TEs). Most TEs studied to date are relatively small (50 – 12000 bp), but can contribute to very large proportions of genomes. Here we report the discovery of a giant tyrosine-recombinase-mobilized DNA transposon, Enterprise, from the model fungus Podospora anserina. Previously, we described a large genomic feature called the Spok block which is notable due to the presence of meiotic drive genes of the Spok gene family. The Spok block ranges from 110 kb to 247 kb and can be present in at least four different genomic locations within P. anserina, despite what is an otherwise highly conserved genome structure. We have determined that the reason for its varying positions is that the Spok block is not only capable of meiotic drive, but is also capable of transposition. More precisely, the Spok block represents a unique case where the Enterprise has captured the Spoks, thereby parasitizing a resident genomic parasite to become a genomic hyperparasite. Furthermore, we demonstrate that Enterprise (without the Spoks) is found in other fungal lineages, where it can be as large as 70 kb. Lastly, we provide experimental evidence that the Spok block is deleterious, with detrimental effects on spore production in strains which carry it. In contrast to the selfish role of the Enterprise in P. anserina, we hypothesize that the mobility of the Enterprise may also play an adaptive role in fungi when Enterprise undergoes horizontal transfer while carrying metabolic genes. This union of meiotic drivers and a transposon has created a selfish element of impressive size in Podospora, challenging our perception of how TEs influence genome evolution and broadening the horizons in terms of what the upper limit of transposition may be.

The insertion of a mitochondrial selfish element into the nuclear genome and its consequences

Homing endonucleases (HE) are enzymes capable of cutting DNA at highly specific target sequences, the repair of the generated double-strand break resulting in the insertion of the HE-encoding gene (“homing” mechanism). HEs are present in all three domains of life and viruses; in eukaryotes, they are mostly found in the genomes of mitochondria and chloroplasts, as well as nuclear ribosomal RNAs. We here report the case of a HE that accidentally integrated into a telomeric region of the nuclear genome of the fungal maize pathogen Ustilago maydis. We show that the gene has a mitochondrial origin, but its original copy is absent from the U. maydis mitochondrial genome, suggesting a subsequent loss or a horizontal transfer from a different species. The telomeric HE underwent mutations in its active site and lost its original start codon. A potential other start codon was retained downstream, but we did not detect any significant transcription of the newly created open reading frame, suggesting that the inserted gene is not functional. Besides, the insertion site is located in a putative RecQ helicase gene, truncating the C-terminal domain of the protein. The truncated helicase is expressed during infection of the host, together with other homologous telomeric helicases. This unusual mutational event altered two genes: the integrated HE gene subsequently lost its homing activity, while its insertion created a truncated version of an existing gene, possibly altering its function. As the insertion is absent in other field isolates, suggesting that it is recent, the U. maydis 521 reference strain offers a snapshot of this singular mutational event.

Complex Transmission Patterns and Age-Related Dynamics of a Selfish mtDNA Deletion

Despite wide-ranging implications of selfish mitochondrial DNA (mtDNA) elements for human disease and topics in evolutionary biology (e.g., speciation), the forces controlling their formation, age-related accumulation, and offspring transmission remain largely unknown. Selfish mtDNA poses a significant challenge to genome integrity, mitochondrial function, and organismal fitness. For instance, numerous human diseases are associated with mtDNA mutations; however, few genetic systems can simultaneously represent pathogenic mitochondrial genome evolution and inheritance. The nematode Caenorhabditis briggsae is one such system. Natural C. briggsae isolates harbor varying levels of a large-scale deletion affecting the mitochondrial nduo-5 gene, termed nad5Δ. A subset of these isolates contains putative compensatory mutations that may reduce the risk of deletion formation. We studied the dynamics of nad5Δ heteroplasmy levels during animal development and transmission from mothers to offspring in genetically diverse C. briggsae natural isolates. Results support previous work demonstrating that nad5Δ is a selfish element and that heteroplasmy levels of this deletion can be quite plastic, exhibiting high degrees of inter-family variability and divergence between generations. The latter is consistent with a mitochondrial bottleneck effect, and contrasts with previous findings from a laboratory-derived model uaDf5 mtDNA deletion in C. elegans. However, we also found evidence for among-isolate differences in the ability to limit nad5Δ accumulation, the pattern of which suggested that forces other than the compensatory mutations are important in protecting individuals and populations from rampant mtDNA deletion expansion over short time scales.

A maternal-effect genetic incompatibility in Caenorhabditis elegans

Selfish genetic elements spread in natural populations and have an important role in genome evolution. We discovered a selfish element causing a genetic incompatibility between strains of the nematode Caenorhabditis elegans. The element is made up of sup-35, a maternal-effect toxin that kills developing embryos, and pha-1, its zygotically expressed antidote. pha-1 has long been considered essential for pharynx development based on its mutant phenotype, but this phenotype in fact arises from a loss of suppression of sup-35 toxicity. Inactive copies of the sup-35/pha-1 element show high sequence divergence from active copies, and phylogenetic reconstruction suggests that they represent ancestral stages in the evolution of the element. Our results suggest that other essential genes identified by genetic screens may turn out to be components of selfish elements.

A parasitic selfish gene that affects host promiscuity

Selfish genes demonstrate transmission bias and invade sexual populations despite conferring no benefit to their hosts. While the molecular genetics and evolutionary dynamics of selfish genes are reasonably well characterized, their effects on hosts are not. Homing endonuclease genes (HEGs) are one well-studied family of selfish genes that are assumed to be benign. However, we show that carrying HEGs is costly for Saccharomyces cerevisiae , demonstrating that these genetic elements are not necessarily benign but maybe parasitic. We estimate a selective load of approximately 1–2% in ‘natural’ niches. The second aspect we examine is the ability of HEGs to affect hosts' sexual behaviour. As all selfish genes critically rely on sex for spread, then any selfish gene correlated with increased host sexuality will enjoy a transmission advantage. While classic parasites are known to manipulate host behaviour, we are not aware of any evidence showing a selfish gene is capable of affecting host promiscuity. The data presented here show a selfish element may increase the propensity of its eukaryote host to undergo sex and along with increased rates of non-Mendelian inheritance, this may counterbalance mitotic selective load and promote spread. Demonstration that selfish genes are correlated with increased promiscuity in eukaryotes connects with ideas suggesting that selfish genes promoted the evolution of sex initially.