Some biochemists and molecular biologists have a Trekkie streak. Not long ago, they discovered Borgs (large libraries of genes in the soil accessed by microbes; see here and here). Now, Starships have landed in the literature. What are they, and what are they doing on our planet?
SETI enthusiasts sometimes think of space aliens as benefactors. Having evolved so many millions of years ahead of humans, and having outlived their own threats of global extinction, they would surely want to share their accumulated wisdom with us, and perhaps even come to Earth to serve man. Others fear space aliens as selfish monsters that would destroy us in a Darwinian fitness contest. Both attitudes are being expressed about the new Starships. What are they? Basically, they are “active eukaryotic transposable elements mobilized by a new family of tyrosine recombinases,” as explained in PNAS. The authors, from Sweden and Australia, are beginning to think these transposons are not all out to get us. Maybe some of them truly are here to serve man.
Converse to many transposons in prokaryotes that include within them genes providing benefits to their new hosts, transposons in eukaryotes have historically been considered selfish pieces of DNA. If Starships are indeed active host-beneficial transposons in fungi, they would closely parallel Integrative and Conjugative Elements in Bacteria and represent a major turning point in our understanding of fungal adaptation and evolution. The Starships are likely to have major impacts on human activities including the “domestication” of cheese-making fungi, increasing tolerance to anthropogenic environmental contaminants and most dramatically causing the emergence of novel plant diseases. By demonstrating the transposition of a Starship experimentally and identifying the enzyme responsible, we take an important step forward in our understanding of these elements. [Emphasis added.]
A meeting with the Captain in this Starship enterprise allays some fears.
Transposable elements in eukaryotic organisms have historically been considered “selfish,” at best conferring indirect benefits to their host organisms. The Starships are a recently discovered feature in fungal genomes that are, in some cases, predicted to confer beneficial traits to their hosts and also have hallmarks of being transposable elements. Here, we provide experimental evidence that Starships are indeed autonomous transposons, using the model Paecilomyces variotii, and identify the HhpA “Captain” tyrosine recombinase as essential for their mobilization into genomic sites with a specific target site consensus sequence. Furthermore, we identify multiple recent horizontal gene transfers of Starships, implying that they jump between species.
Captain HhpA assures the biochemists that his crew is not selfish. The Starships have a mission: to explore strange new genomes, to seek out new fungi and new eukaryotes, and to boldly go where no transposon has gone before.
Information Is for Sharing
Like the Borgs, which appear to be “storage lockers” of genetic information accessible to multiple organisms in the soil, Starships bring the accumulated wisdom of the ages to eukaryotes. Bacteria were already known to benefit from their transposons, called ICEs (Integrative and Conjugative Elements). They’re not all bad.
ICEs are mobile DNA (~20 Kbp to >500 Kbp in size) that contain the genes required for genomic integration, excision, and transfer via conjugation. In addition, they contain a wide range of gene cargos conferring phenotypes such as antibiotic resistance, heavy metal resistance, nutrient utilization, and pathogenicity.
It’s time for eukaryotes like us to look at our transposons anew. Remember all those transposable elements, those parasitic “jumping genes” and ubiquitous Alu elements that evolutionists have been telling us are “selfish genes” that accumulate as “junk” in our DNA? Have we been guilty of systemic geneism? We should learn to be more tolerant and inclusive of the elements giving us genetic diversity.
But Can We Trust Them?
The relative proportion of Starships carrying host-beneficial vs. neutral vs. deleterious cargo remains to be determined, and such contributions to fitness will depend on the environment in which the organism is growing. It has thus been proposed that Starships represent eukaryotic analogs of prokaryotic ICEs. A striking parallel between Starships and ICEs is that they often possess signatures of HGT [Horizontal Gene Transfer]. The vast number of sequenced genomes has led to the realization of recurrent HGT within fungi. Furthermore, these transfers are not limited to individual genes, but often encompass entire gene clusters. Many of these cases have since been predicted to involve Starship elements, uniting many disparate observations under a single phenomenon, and implicating Starships as vehicles of HGT in fungi.
Since fungi are ubiquitous in the world, their accumulated knowledge bases can spread to higher organisms. Perhaps they work together with Borgs, checking out library books and putting them in an organism’s personal library. The authors give several examples of Starships with their own Captain proteins that appear to benefit their hosts.
The First Starships Land
The term Starship for eukaryotic transposable elements (TE) stems from a paper in Molecular Biology and Evolution in which the authors suggested that they are analogs of bacterial TE’s with the following functions:
We propose that Starships are eukaryotic analogs of bacterial integrative and conjugative elements based on parallels between their conserved components and may therefore represent the first dedicated agents of active gene transfer in eukaryotes. Our results suggest that Starships have shaped the content and structure of fungal genomes for millions of years and reveal a new concerted route for evolution throughout an entire eukaryotic phylum.
One of the co-authors of that paper also appears in the new PNAS paper, which began as a preprint on bioRxiv last August. Two years ago, Aaron A. Vogan of Uppsala University met the familiar Captain of a Starship:
Vogan et al. showed that the Captain protein KIRC has some similarity to YRs, but sequence identity between KIRC and HhpA is low (~14%). To investigate the Captain proteins further we computationally predicted structures using AlphaFold. The predictions showed considerable similarity for KIRC and HhpA (HhpA aa 8 to 671, KIRC aa 1 to aa 584, TM-score 0.71) as well as between HhpA and Cre recombinase (HhpA aa 39 to 431, KIRC aa 33 to aa 341, TM-score 0.59) (Fig. 2G). This strengthens the evidence that these two Captain proteins share a common function and that they both represent tyrosine recombinases.
Vogan has been busy drawing parallels to Star Trek. His 2021 paper referenced above is titled, “The Enterprise: a massive transposon carrying Spok meiotic gene drives.”
Some twenty Starship sites have been identified, according to the paper, but hundreds more may await discovery. The authors believe that Starship families (fleets?) are at work transferring genes horizontally between species of fungi.
How Starships Perform Their Prime Mission
The Captain proteins in Starships open up sites in fungal genomes for insertion of genetic information, which can range from 27 to 393 kilobases in size. Genomes have defenses against transposable elements, suggesting a conflict of forces requiring terms of peace. One subsection of the paper is entitled, “Benefits Carried by Starship Transposons Are in Tension with Host Genome Defenses That Protect Against Mobile DNA.”
Starships such as Hφ embody an inherent tension between their selfish properties; i.e., their mobility which is something that fungi typically employ defenses against and their cooperative properties, i.e., the host-beneficial genes they may contain…. We hypothesize that the resolution to this apparent paradox lies in consideringhorizontal transfer not as an oddity but as a fundamental feature in the lifecycle of host-beneficial Starships.
Accustomed as they are to thinking in Darwinian terms, the authors speak of selfishness, fitness, selective advantages, and survival in one paragraph, saying little else about those things for most of the paper. But of attempts to incorporate them into evolution, they admit that “Such hypotheses provide another frontier for further exploration.” Many of these Starshipelements show strong conservation even though presumed to have been around for hundreds of millions of years.
Serving Fungi Serves the Biosphere
Just as Borgs opened the possibility that large genetic libraries are being shared between organisms outside of cells, Starships now create a new paradigm for transposable elements within and between genomes. As with bacterial TEs, Starships acquire and disperse accessory genes as cargo. Some of the Starships are huge; they carry information on a variety of functional benefits to organisms. The 2022 paper suggests that Starships:
- Provide accessory genes from one species to another
- Offer standing genetic variation in structure and content for adaptation
- Add virulence factors for parasitic and saprophytic growth
- Confer protection from antibiotics, chemicals and pathogens
The authors summarize what studies have found so far:
Large DNA regions, dubbed “Starships,” have recently been hypothesized to act as host-beneficial eukaryotic transposons. Previously, we have demonstrated a beneficial effect of Hφ in increasing metal ion tolerance. Now we demonstrate the mobility of Starship elements and show that this movement is mediated by the Captain tyrosine recombinase. Furthermore, the identification of a near-identical Starship in the genomes of two different fungal species is compelling evidence that these elements move not only within a genome but also between species.
The authors believe that they have “only scratched the surface of the role of Starship-mediated HGT in fungi, i.e., by examining the most obvious cases in a single Starship family — Hφ.” And as beneficial TEs in prokaryotes had started dissolving the old “selfish gene” notion, now they are seeing similar host-beneficial operations in eukaryotes. “Bioinformatic exploration of genome sequences indicates that Starships are a pervasive phenomenon” in fungi so far, but who knows what other surprises lie ahead? The “study of Starships represents an exciting avenue toward increasing our understanding of how fungi rapidly evolve numerous traits that impact upon human activities.” Since higher organisms are increasingly known to engage in HGT, will scientists find Starships: The Next Generation at work throughout the biosphere?
Implications for Intelligent Design
This is not your grandfather’s neo-Darwinism. Where are the random mutations? Where is the natural selection? The sharing of information is not evolution in the Darwinian sense. By taking the Darwin glasses off, one might see systems at work allowing for prefabricated adaptation to new surroundings. Instead of Darwin’s meaningless world, it looks increasingly like a world engineered for adaptability by an intelligent cause exercising foresight. With that worldview in mind, ID scientists could take the lead on this exciting endeavor.