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Selfish Genes in Nematodes

1:15:20 recording · AUTO · 2 speakers

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Brief overview

Selfish toxin-antidote genes in C. tropicalis arose from duplicated tRNA synthetases pre-suppressed by ubiquitin ligase antidotes.

  1. The antidote comes first, then the toxin is toleratedPre-suppression explains how a toxin gene can arise without crashing its own lineage before an antidote exists.
  2. Antidotes are E3 ubiquitin ligases that degrade the toxinKSS proteins ubiquitinate Puzzle 1 and Klimt 1 for the proteasome, a mechanism Nels had not seen in toxin-antidote systems before.
  3. Selfish elements may seed antiviral genesNels' lab found flavivirus-blocking E3 ligases next to selfish elements in reptile genomes, suggesting antidotes can be repurposed against viruses.
Executive Summary AI
  • Vincent Racaniello and Nels Elde open Twevo episode 122 with a paper from Alejandro Berga's group at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences in Vienna, first author Polina Tikhanova, titled Recurrent Evolution of Selfishness from an Essential tRNA Synthetase in the nematode C. tropicalis, whose first sentence reads 'No genome on Earth is free of selfish genes.'16:37
  • Nels lays out the paper's two ideas: pre-suppression, where the antidote exists first and creates room for a toxin to emerge already neutralised and linked to it, and constructive neutral evolution, where complexity accumulates through random mutation without natural selection driving it.27:13
  • The toxins Puzzle 1 (PZL1) and Klimt 1 match a phenylalanine tRNA synthetase subunit in AlphaFold, while the antidotes KSS1 and KSS2 are F-box proteins at 50% sequence identity resembling Skp1-family E3 ubiquitin ligases, and AlphaFold Multimer, co-immunoprecipitation with mass spec and a GFP-tagged toxin all support the antidote tagging the toxin for degradation by the proteasome.37:00
  • Comparing about a dozen related species the authors find some 600 copies of these gene families with signatures of rapid evolution, infer that Puzzle 1 and KSS2 were the founding pair with Klimt 1 and Hyde 1 arriving later, and Nels ties this to his own lab's newly described E3 ubiquitin ligases that block flaviviruses and sit next to selfish elements in an iguana genome.49:14
  • For picks, Nels recommends JP Flores' podcast From Where Does It STEM and his co-founding of Stand Up for Science, and Vincent recommends Ross Anderson's Atlantic article An Act of Cosmic Sabotage on Trump calling for 40 of NASA's 124 science missions, including Mars sample return, to be defunded.1:03:20
Key Quote
“No genome on Earth is free of selfish genes.”
— Vincent Racaniello18:19
Key Quote
“Plenty of confidence and very little competence.”
— Nels Elde13:48
Key Quote
“Choosing the right organism for one's research is as important as finding the right problems to work on.”
— Nels Elde25:22