Story Nudge

Written by Rolf Brudvik Edvardsen

Background:

Although specific gene editing has been possible for some time, the methods (Zink-finger nucleases (ZFN) and Transcription activator-like effector nucleases (TALENS) have suffered from low efficeny and high costs. The advent of CRISPR has enabled an efficient way of modulating the genome at a low cost in any organism. This includes not only knocking out genes, but also the poissibility to insert DNA (knock-in), even from other species.

Knock-in of genes has already been done in fish for human consumption. More specifically, it has been done in salmon to produce a fish that grows faster than un-modified strains (AquAdvantage salmon produced by Aquabounty, https://aquabounty.com/). This fish is approved for sales in some countries, including the US.

The Marbled lungfish (there are also 5 other lungfish species, but with smaller genomes) genome is huge. The 133 Gb genome is the largest in any vertebrate, and one would have to go to plants and the 150 Gb Paris japonica or to the primitive Amoeba dubia which has a 670 Gb genome.. But despite its large size the lungfish genome seems to harbour the same number of genes (20-25,000) found in most other vertebrates, including human (Reference: http://www.nature.com/articles/srep21571). There are exceptions to this number, but this is not related to either genome size or how “advanced/evolved” the species is. For example, the salmonids have about 45,000 genes due to a recent whole genome duplication specific to this this lineage (ref: http://www.nature.com/nature/journal/v533/n7602/full/nature17164.html). The discrepancy between genome size and complexity of the species is referred to as the C-value paradox and has for long been just hat, a paradox. But with the genome sequencing of many species it is apparent that what was earlier believed, that the genome size and number of genes was linear, is wrong. The genomes contain vast quantities of non-protein-coding DNA. Also, the number of genes is not explaining the complexity of the organism. So, what is that gives rise to the complexity? Why are still some genomes big?  What are the functions of the non-coding DNA? These questions are still largely unexplained and are called the C-value enigma (ref: http://rstb.royalsocietypublishing.org/content/370/1678/20140331).

 

Lungfish as carrier of other species:

The lungfish genome is so big that it has not been completely sequenced. Still, a reference transcriptome (a catalogue of genes in use) suggest a normal number of genes, meaning that there must a lot of “other stuff” there. A study looking at a small portion of the genome (https://www.ncbi.nlm.nih.gov/pubmed/22734051?dopt=Abstract&holding=npg) showed that the genome contains a large number of transposable elements (TEs) and that most of these probably are old and silent (non-functional). A removal of these would therefore probably have little or no effect (my speculation). Also, the large size of the genome seems to not be a problem for lungfish. Take together this implies that either replacement of part of the genome with foreign DNA or just adding foreign DNA would not cause a problem for the fish in it self. But if one just insert a genome from another species into the lungfish genome there could still be a problem if these genes are transcribed (used). To prevent this one would have to make sure that the foreign DNA is silenced some how. DNA can be silenced by silencing elements which are important in regulating that not all genes are expressed in all cells in the body. But here we are talking about large regions. Large regions can be silenced by packing the DNA densely into what is known as heterochromatin (https://en.wikipedia.org/wiki/Heterochromatin). This could possibly be obtained by inserting the DNA into certain regions of the lungfish genome known to be inactivated (often close to the centromere or telomers (middle and ends) of the chromosomes). Or one could insert many silencing elements into the foreign DNA. Still, and important for the story, some genes within the silenced regions can be activated under specific developmental or environmental cues.

 

Bottom line; it is possible, using CRISPR technology, to insert foreign DNA or even whole genomes of other species into the lungfish genome without any effect on the lungfish.

One can then imagine that the lungfish can act as a Noah’s ark carrying other species to mars. This is advantageous in many ways. It is not possible for many species to survive the long trip to mars, and it would require much infrastructure to make appropriate facilities for each of the species which has different needs in terms of food, temperature, salinity etc. Once at mars one can use lungfish eggs to produce other species. This is done by removing the lungfish DNA from the eggs (or inactivating the DNA by x-ray, both methods possible, and done today) and then inject DNA from other species which has been excised from the lungfish genome. The lungfish egg would then develop into for example a salmon.

One can naturally also carry other species than fish in the genome of lungfish. But then it would probably not work to use the lungfish eggs to grown these species. But for one other species there is a solution: human. Since there already are humans on mars there are therefore eggs available. To increase the human population on mars without reaching a bottleneck (there are so few humans on mars meaning that the genetic pool is limited, something which is a hazard) it would be beneficial to mix other populations DNA into the population on mars. Also, there is political pressure to include all humans from all countries in the mars colony.

There could be several tanks with lungfish on board. Some with DNA from other fish species (so that one can try out these species for aquaculture on mars), some with DNA from humans, and some lungfish that has been modified to high nutritional value for consumption (on mars or on route). Do not eat from the wrong tank or you can kill off an entire population!

On the trip, some things may happen which was not foreseen. The specific environment in space (temperature/light/gravity etc) has triggered some genes from the silence inserted genomes to be expressed. Strange phenotypes can be observed….  Also the radiation from the sun makes unwanted mutations in the genome which leads to……

A side note: on Svalbard there is now a storage for plant seeds from all over the world. Also there is a new storage for data to be kept for a thousand years. In the future there could/should (in my opinion) be a storage also for DNA from all species. If could imagine that this was in place, but the climate change has made the now stable cold and storage-friendly climate too warm for safe keeping, and the only safe place is to move/copy the information into lungfish for transport to the new facility on mars. (here the drawback is that only a couple of freezers on board the space ship would do the trick).

 

-Rolf