Essentials: Genes & the Inheritance of Memories Across Generations | Dr. Oded Rechavi

Genes, RNA, and Proteins

• DNA is the genetic instruction set (the genome) present in every cell; chromosomes are DNA condensed with proteins, like thread on a spool.
• Analogy: the genome is the IKEA book; RNA is the specific page copied for one item; the protein is the finished furniture.
• Less than 2% of the genome encodes messenger RNA; much of the rest is transcribed into RNAs whose functions are partly unknown.

Soma versus Germline

• Germ cells (sperm and egg) are the only cells that form the next generation; everything else is soma.
• Changes in somatic cells, like brain synapses or muscles built at the gym, cannot reach the germ cells, which blocks inheritance of acquired traits.

Barriers to Inheritance

• The Weismann Barrier (August Weismann, 19th century) separates soma from germline; it is called the second law of biology.
• Epigenetic reprogramming erases about 90% of chemical modifications in sperm, egg, and early embryo, giving each generation a blank slate.
• Lamarck proposed inheritance of acquired traits (giraffes stretching necks); Darwin showed natural selection of existing heritable variation instead.

C. elegans as a Model

• The worm has exactly 959 cells, 302 named neurons, a complete connectome since the 1980s, is transparent, and has a three-day generation time.
• Each mother produces about 250 genetically identical babies, enabling controlled experiments separating nature from nurture.

RNA Interference

• Fire and Mello (Nobel Prize 2006) showed double-stranded RNA silences matching genes; the effect spreads body-wide and into the next generation.
• Worms can be fed bacteria producing double-stranded RNA, and silencing moves from the gut to progeny.

Inherited Traits via Small RNAs

• Rechavi's lab infected worms with a fluorescent virus; descendants lacking small RNA machinery still silenced the virus because they inherited matching small RNAs from parents, lasting multiple generations.
• A 2019 Cell paper: changing small RNA production only in the brain altered food-finding behavior for three generations, acting through the germline gene SAGE2.
• Worms amplify small RNAs to prevent dilution; no amplification mechanism is known in mammals.

Future Directions

• Possible RNA-based diagnostics for couples, and perhaps interventions (e.g., exercise) to change heritable RNA profiles before IVF — all speculative for humans.