DNA fragility in the parallel evolution of pelvic reduction in stickleback fish
Let’s look at what they did.
In previous work, long stretches of alternating pyrimidine/purine repeats have been shown to form Z-DNA: pnas.org/content/80/7/1…
The authors don't say, but I speculate that they could form G-quadruplexes (of the unimolecular bulged variety). G-quadruplexes are implicated in genomic instability. nature.com/articles/nrm.2…
- sequence rearrangements (turns mutation “on/off” at a loci)
- change in DNA replication direction (turns mutation “on/off” at a loci)
1) TG-repeats flanking an enhancer regulating a gene for a phenotype
2) Exploiting the inherent fragility of TG-repeats during DNA replication (+direction)
3) Fragility leading to DNA breaks
5) This is supported by population genetic modelling: showing that it's possible for vertebrates to rapidly adapt to new environments despite small population sizes.
- what is the biochemical/biophysical basis for direction dependent TG-repeat fragility?
- when is the Pel loci open to mutation? When is it not?
- how much of the phenotypic variation we see in natural pops is due these type of de novo mutations?
∴ the authors reverse URA3 transcription direction to determine this impacts fragility.
Thank you everyone! The response to this has been overwhelming! I hypothesised that there was a latent hunger in the twitter science community for paper breakdowns. That hypothesis still stands. This thread even reached non-scientists – something I never expected.
It was a joy reading this beautiful paper. Additionally, it was a rewarding experience trying to disassemble it, examine each part (a lot of which I knew little about prior to reading), & reassembling it in my own words for a general audience.
So, next time you come across a paper that you find interesting, why not have some fun and #tweetapaper?