Hosted by Lester Nare and Krishna Choudhary, this episode marks
Krishna’s return to the studio after paternity leave — and the
timing could not be more fitting. Today’s deep dive is about
inheritance: not just the classic Mendelian rules most of us
learned in biology class, but the stranger, more dynamic world of
non-Mendelian epigenetic inheritance. Starting from Gregor Mendel
and his pea plants, Lester and Krishna rebuild the foundations of
genetics from first principles: dominant and recessive alleles,
Punnett squares, chromosomes, fruit flies, DNA, and the physical
mechanism behind inherited traits. Then they move into the
“software layer” of biology: epigenetics, DNA methylation,
chromatin packaging, RNA interference, and paramutation — cases
where the genetic code is present, but the cell’s machinery
silences or rewrites how that code is used. The episode centers on
a new Nature Genetics paper, “Non-Mendelian inheritance of DNA
methylation patterns in mice,” which suggests that non-Mendelian
epigenetic inheritance may be more widespread in mammals than
previously understood. The conversation also covers why Oxford
Nanopore sequencing made this kind of analysis possible, why
methylation patterns can be hard to trace across generations, and
what all of this could mean for disease risk, drug response, sex
differences, evolution, and the long-running nature-versus-nurture
debate. Summary Mendel’s rules — how pea plants, true-breeding
lines, dominant and recessive traits, and Punnett squares gave us
the first mathematical laws of inheritance. The first cracks in
Mendel — how chromosomes, fruit flies, sex-linked traits, and
linked genes showed that inheritance is more complicated than
independent assortment. DNA as hardware, epigenetics as software —
why having a gene is not the same thing as expressing it, and how
methylation and chromatin packaging can silence parts of the
genome. Paramutation — how one allele can change the expression
state of another allele across generations, creating inheritance
patterns that do not follow standard Mendelian expectations. Oxford
Nanopore and the technology shift — why long-read sequencing and
direct methylation detection make it possible to trace epigenetic
marks back to the parent they came from. The mouse methylation
paper — how researchers used collaborative cross mice to show that
most methylation inheritance looks Mendelian, but a meaningful
fraction appears to follow stranger non-Mendelian rules. Why it
matters — potential implications for clinical genetics, disease
risk, drug efficacy, sex-specific biology, and the relationship
between nature and nurture. Support the show Donate:
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