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by iten 2377 days ago
I recently completed my PhD in vertebrate comparative genomics so this is fun to see.

The single most important factor that needs to be accounted for in analyses like these is the correlation between phylogenetic similarity and the trait in question. In short, closely related species will tend to have similar lifespans, and closely related species will tend to have similar CpG density in any fixed genomic region. So the fact that you can predict lifespan from CpG density with enough parameters is unsurprising. You could almost certainly predict lifespan fairly well from any feature measuring phylogenetic similarity -- I would have liked to see some evidence showing that CpG density in these promoters is somehow uniquely suited for the task.

2 comments

They did mention they were looking at a couple of long lived examples like rockfish that live 200 years vs killifish that live for 1, so this seems to be variable among fish at least. As for mechanism, they were pretty hand wavey but cited reference 33 and mentioned that longer CpG tracts are thought to be protective against spontaneous methylation. Unmethylated CpG islands in promotors are associate with active transcription, especially found in housekeeping genes that are transcribed constantly by definition. Methylating these islands can silence the gene. Makes sense but needs an experiment to know for sure.
I wonder whether they also looked at body size. Larger species tend to live longer, so it could just be that their regions are just associated with growth.
They did not.