Episode

The Dark Genome with Author Sudhakaran Prabakaran

Podcast
Mendelspod Podcast
Published
Mar 3, 2026
Duration seconds
2237
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Summary

We began this podcast back around the time the ENCODE project announced that much of the genome was biochemically active. The big science project was undoing the tidy idea of “junk DNA,” and not without controversy. But activity is not the same as purpose. On today’s show, we move past the question of whether the non-coding genome does something and ask a more ambitious one: why has evolution retained so much genomic material unless it carries adaptive potential? Theral speaks with Sudhakaran Prabakaran , computational biologist at Northeastern University and founder of NonExomics, about his provocative new book, “ Eclipsed Horizons: Unveiling the Dark Genome .” Drawing on his lab’s work cataloging more than 250,000 non-canonical proteins, Prabakaran argues that regions outside traditional gene definitions are constantly generating novel open reading frames—previously unrecognized proteins that may shape adaptation, speciation, and disease. Chapters: (00:00) Identical Genomes, Wildly Different Fish (04:00) The Dark Proteome Wakes Up (10:00) Protein Pop-Up Shops (20:00) Homo Minimus and the Space Thought Experiment (30:00) Precision Medicine Beyond the Exome From rapidly diversifying cichlid fishes to human accelerated regions (HARs) of the human genome linked to schizophrenia, he makes the case that protein birth and death is continuous, cheap, and exploratory. In his framing, the “dark genome” functions less like debris and more like a flexible evolutionary sandbox—capable of producing latent biological parts that can be deployed under stress or even extreme environments like spaceflight. The book goes beyond ENCODE’s demonstration of activity and asks what that activity is for, crossing into that taboo in biology, teleonomic analysis. Weaving together proteomics, evo…