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From 'Protein and DNA Sequence Determinants of Thermophilic Adaptation', by Konstantin B Zeldovich, Igor N Berezovsky and Eugene I Shakhnovich (Published: January 12, 2007 | https://doi.org/10.1371/journal.pcbi.0030005):

Proteins are encoded in the nucleotide sequences of their genes, and thermal adaptation presumably leads to increased stability of both proteins and DNA. Therefore, signatures of thermal adaptation in protein sequences can be due to the specific biases in nucleotide sequences and vice versa. In other words, one has to explore whether a specific composition of nucleotide (amino acid) sequences shapes the content of amino acid (nucleotide) ones, or thermal adaptation of proteins and DNA (at the level of sequence compositions) are independent processes.

To resolve this crucial issue, we applied the following logic. If amino acid biases are a consequence of just nucleotide biases and not protein adaptation, then proteomes translated from randomly reshuffled genomes will feature similar “thermal adaptation” trends in amino acid composition as observed in real proteomes. In contrast, if amino acid compositions are selected independently, then such control calculation will result in apparently different amino acid “trends” in randomly reshuffled genomes than observed in reality.


Can someone explain the logic of these authors in the second paragraph? Because I do not understand.

Firstly, I understand that DNA can adapt somewhat independently from proteins due to codon bias, and protein expression can adapt independently from DNA due to epigenetic factors (epigenetics is not mentioned in the article). However, how does comparing the amino acid composition of a proteome translated from a randomly shuffled genome to the original, unshuffled proteome provide insights into independent protein adaptation?

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  • $\begingroup$ I think they explain themselves pretty clearly; think about the two possible scenarios they identify, and how their shuffling experiment will give different results in the two scenarios. $\endgroup$
    – Bryan Krause
    Nov 3, 2023 at 2:53
  • $\begingroup$ @BryanKrause thanks Bryan I have several times, but I still do not understand how the second scenario in particular suggests what the authors are claiming it suggests. This is probably me at fault, but for some reason I can not understand. $\endgroup$ Nov 3, 2023 at 10:52
  • $\begingroup$ Firstly, the researchers say: "proteomes translated from randomly reshuffled genomes will feature similar “thermal adaptation” trends in amino acid composition as observed in real proteomes", this is only a chance, there is a chance that the thermal adaptation trends will be entirely different. I suspect this is probable, because DNA only has four unique nucleotides, read in codons, if one nucleotide in a codon is changed then the entire amino acid could change. This is why I would actually expect "apparently different amino acid “trends”" in the first scenario. $\endgroup$ Nov 4, 2023 at 1:47
  • $\begingroup$ Furthermore, if the genomes are randomly shuffled, how would this suggest: "In contrast, if amino acid compositions are selected independently, then such control calculation will result in apparently different amino acid “trends” in randomly reshuffled genomes than observed in reality."? I would expect the opposite, if the genome was reshuffled and we observed the same amino acid composition, then I could see how protein adaptation is somehow independent from DNA adaptation, as I would expect the amino acid composition to be different, due to new codons being created by the random DNA shuffle. $\endgroup$ Nov 4, 2023 at 1:54

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