The Enterprise: A massive transposon carrying Spok meiotic drive genes

 

Background

Transposable elements (TEs) are mobile genetic elements, which inhabit the genomes of organisms across all the domains of life. TEs are commonly considered selfish genetic elements because their untethered propagation may be detrimental to its host genome. However, it’s important to note that not all TEs are bad guys. Keep in mind that TEs comprise a substantial proportion of the genome in many organisms (~45% in humans and up to 85% in maize). So it can’t be all bad, can it? In fact, such widespread “domestication” has led to an increased recognition of TEs as fundamental elements in shaping genomes and gene expression throughout evolutionary time.

While TEs strive to propagate against the best interests of their hosts, the host tries really hard to silence TEs, and opposed interests such as these are the hallmark of genetic conflicts. TEs by no means hold the monopoly on genetic conflict. In fact, there are many more types of inter- and intragenomic conflict. Another class of genetic conflict is mediated by elements that manipulate normal Mendelian segregation patterns, in order to enhance their representation in the gametes. When this process of segregation distortion occurs during meiosis it is termed meiotic drive.

In the fungi of the genus Podospora, spore killing (or Spok) genes are selfish meiotic driver genes. These genes can be found in large genomic features (110 kb -247 kb) termed Spok blocks. Interestingly, although there is one single copy of a Spok block per Podospora genome, distinct strains of a given Podospora species may have Spok blocks in different locations, in genomes displaying an otherwise high level of synteny. In a recent study, Vogan and colleagues determined the reason for this particular distribution: Spok blocks were captured by a fungal TE, aptly baptized as the Enterprise.

 

Key findings

• The authors first expanded the current set of available Podospora genomes by sequencing the genomes of additional strains. In one of the newly sequenced strains of P. anserina they found the largest Spok block to date, with a formidable 247 kb.
• Taking a closer look at the terminal sequences of Spok blocks, repeat and palindromic sequence signatures were identified. TEs typically display repeats in their extremities, and these are required for transposition. Thus, the existence of such terminal sequences are consistent with Spok block mobilization via transposition, which provides an explanation to their distinct genomic locations.
• Annotation of the Spok blocks did not show genes typically associated with TE mobilization, like transposases or reverse transcriptases. Instead, Spok blocks include many non-repetitive genes, with potential functions in diverse metabolic pathways. Progressive accumulation of non-repetitive genes over many rounds of transpositions was proposed as a mechanism to increase the size of Spok blocks.
• The authors further identify in P. comata a shorter 39 kb TE with some similarity to Spok blocks and their terminal repeats, which they named as the Enterprise. Within the Enterprise, they found a gene with homologs in every known Spok block. Going ever deeper into their Star Trek homage, the authors named this new gene as Kirc, which has predicted structural similarity to a transposon that mobilizes via a tyrosine recombinase mechanism. Overall, this suggests that Enterprise are TEs mobilized by Kirc genes.
• Lastly, the authors perform genetic crosses between a number of spore killer and non-killer strains and conclude that the Spok block may be deleterious due to their genomic location, but not because of their content or size.

 

What I like about this preprint

I really enjoyed this preprint because it challenges some of the ways in which we look at TEs. Generally, TEs are no larger than 10-12 kb. And while large TEs have been described, the Spok block pushes the upper boundary of TE size by almost 100 kb. Are we missing even larger TEs out there? Also, I love the philosophical question raised by the authors in the discussion: who is parasitizing whom? The capture of Spok meiotic drivers by Enterprise TEs, two independently selfish genetic elements, leads to the creation of a genomic hyperparasite, a term put forward by the authors. This is the first time I have heard about two drivers of genetic conflict coming together and it raises many questions regarding the selective pressures operating against these elements.

Last but not least, I must confess I am a sucker for funny gene names. Building from Spok, the finding of an Enterprise TE carrying these elements evidently is meaningful and produces an excellent metaphor, as these TEs navigate and explore fungal genomes, much like Starship Enterprise and its crew roamed space in the Star Trek universe. Since particular TEs were shown to mediate horizontal gene transfer of their cargo genes, it remains to be determined if the Enterprise TE is indeed carrying its large cargo beyond the species barrier and going boldly where no Spok has gone before.

 

Open questions

• So far four types of Spok genes have been described (Spok1-4). Spok3/4 are always in the context of the Spok block while Spok1/2 are not. Does this reflects phylogeny? That is, do you think that Spok3/4 are derived from an ancestor that was captured by Enterprise TEs, whereas the ancestor of Spok1/2 remained independent?
• Contrary to Spok1/2, Spok blocks do not reach high frequencies in the population. Is this perhaps demonstrating the conflict between hosts and Spok blocks? Are Spok blocks under more strict control than their Enterprise-less counterparts? In this sense, do you know whether Podospora express RNAi machinery (Argonautes, RNA-dependent RNA Polymerases, Dicer) and small RNAs complementary to Spok blocks?
• All Spok blocks have Kirc genes. To support your hypothesis that Spok blocks accumulate more and more non-repetitive genes over time, would it make sense to look at sequence divergence of Kirc genes to estimate Spok block age? If true, the age of the Spok block would correlate with size.

 

In these daunting times we live in, take care of yourselves and your loved ones.

And of course…

Live long and prosper.

 

Want to know more?

Regulatory activities of transposable elements: from conflicts to benefits, Chuong et al., 2016

https://www.nature.com/articles/nrg.2016.139

 

Combinations of Spok genes create multiple meiotic drivers in Podospora, Vogan et al., 2019

https://elifesciences.org/articles/46454

 

Selfish genetic elements, Ågren & Clark, 2018

https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007700

 

Tags: enterprise, meiotic drive, podospora, spok block, spok genes, transposable elements

doi: https://doi.org/10.1242/prelights.18223

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