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Genetics & DNA — Mendel to CRISPR

DECK / 5'-GENETICS-3' 2026 / SCIENCE // THE MOLECULAR ARCHIVE GENETICS / The Four-Letter Alphabet From a monastery garden to programmable molecules — how...

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DECK / 5'-GENETICS-3' 2026 / SCIENCE // THE MOLECULAR ARCHIVE GENETICS / The Four-Letter Alphabet From a monastery garden to programmable molecules — how four bases (A, T, G, C) became the operating system of life. Key sections include: GENETICS / The Four-Letter Alphabet; Mendel's Peas; The Double Helix; DNA → RNA → Protein; 64 codons → 20 amino acids; The Human Genome Project; "Junk" DNA, reconsidered; Mutations: the source code of variation; PCR: the photocopier of biology; Reading DNA: 100,000× cheaper.

Key sections

  • 01GENETICS / The Four-Letter Alphabet
  • 02Mendel's Peas
  • 03The Double Helix
  • 04DNA → RNA → Protein
  • 0564 codons → 20 amino acids
  • 06The Human Genome Project
  • 07"Junk" DNA, reconsidered
  • 08Mutations: the source code of variation
  • 09PCR: the photocopier of biology
  • 10Reading DNA: 100,000× cheaper
  • 11CRISPR-Cas9 programmable editing
  • 12The programmable body
  • 13References & further reading

Topics covered

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Slide outline
  1. 01GENETICS / The Four-Letter Alphabet
  2. 02Mendel's Peas
  3. 03The Double Helix
  4. 04DNA → RNA → Protein
  5. 0564 codons → 20 amino acids
  6. 06The Human Genome Project
  7. 07"Junk" DNA, reconsidered
  8. 08Mutations: the source code of variation
  9. 09PCR: the photocopier of biology
  10. 10Reading DNA: 100,000× cheaper
  11. 11CRISPR-Cas9 programmable editing
  12. 12The programmable body
  13. 13References & further reading
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Slide 01

GENETICS / The Four-Letter Alphabet

  • DECK / 5'-GENETICS-3'
  • 2026 / SCIENCE
  • // THE MOLECULAR ARCHIVE
  • From a monastery garden to programmable molecules — how four bases (A, T, G, C) became the operating system of life.
  • 5'ATGCATGAAGAT...3'
Slide 02

Mendel's Peas

  • 02 / FRAME
  • 1866 — BRNO
  • Frame 02 / Origin
  • In an Augustinian monastery in Brno, Gregor Mendel cross-bred 28,000 pea plants and discovered that traits were inherited as discrete particles — not blended liquids.
  • Dominant & recessive alleles (3:1 ratios)
  • Independent assortment — separate traits
  • Particulate inheritance — units, not fluids
  • Published 1866. Ignored for 34 years, until rediscovered in 1900
  • P × P → F1 → F2
  • P: YY × yy (yellow × green)
  • F1: Yy Yy Yy Yy (all yellow)
  • F2: YY Yy Yy yy → 3 : 1
  • A monk's data table that, decades later, would name a science.
Slide 03

The Double Helix

  • 03 / FRAME
  • 1953 — CAMBRIDGE
  • Frame 03 / Structure
  • April 1953, Nature: Watson & Crick publish a one-page paper proposing DNA's antiparallel double helix — built on Rosalind Franklin's X-ray crystallography (Photo 51).
  • Two strands wound around a common axis
  • Bases pair inside: A↔T, G↔C
  • Franklin: the experimental backbone of the discovery
  • "It has not escaped our notice…" — replication mechanism implicit
Slide 04

DNA → RNA → Protein

  • 04 / FRAME
  • CENTRAL DOGMA
  • Frame 04 / Information Flow
  • Crick's 1958 "central dogma": genetic information flows in one direction. DNA stores it, RNA transports it, ribosomes translate it into the molecular machines (proteins) that do the work.
  • Replication
  • DNA → DNA. Polymerases unzip the helix and copy each strand semi-conservatively before cell division.
  • ATGC ⇋ TACG
  • Transcription
  • DNA → mRNA. RNA polymerase reads a gene; thymine (T) becomes uracil (U).
  • ATGC → AUGC
  • Translation
  • mRNA → protein. Ribosomes read codons (3 bases) and chain amino acids into a folded protein.
  • AUG = Met · start
Slide 05

64 codons → 20 amino acids

  • 05 / FRAME
  • THE CODE
  • Frame 05 / Codon Table
  • Three-letter words spell every protein in every species. The code is redundant (multiple codons per amino acid) and nearly universal — bacteria, ferns, and humans share it.
  • AUG = start codon (Met)
  • UAA / UAG / UGA = stop codons
  • Cracked 1961–66 by Nirenberg, Khorana, Holley
  • AUGMet·M
  • UUUPhe
  • UUCPhe
  • UCUSer
  • UCCSer
  • UAUTyr
  • UAASTOP
  • UAGSTOP
  • CUULeu
  • CUCLeu
  • CUALeu
  • CCUPro
  • CAUHis
  • CAAGln
  • CGUArg
  • CGCArg
  • AUUIle
  • ACUThr
  • AAUAsn
  • AAALys
  • AGUSer
  • AGAArg
  • GUUVal
  • GCUAla
  • GCCAla
  • GAUAsp
  • GAAGlu
  • GGUGly
  • GGCGly
  • GGAGly
  • UGGTrp
  • UGASTOP
  • Excerpt — 32 of 64 codons shown.
Slide 06

The Human Genome Project

  • 06 / FRAME
  • 1990–2003
  • Frame 06 / The Atlas
  • Thirteen years, 20 institutions, $2.7 billion. Completed in 2003 — a complete reference of human DNA. The biggest surprise wasn't what it contained, but how little.
  • 3.0B
  • Base pairs in the human genome
  • ~20,000
  • Protein-coding genes (fewer than expected)
  • Of DNA actually codes for proteins
  • For comparison: a rice plant has ~32,000 protein-coding genes. Complexity isn't about gene count — it's about regulation.
Slide 07

"Junk" DNA, reconsidered

  • 07 / FRAME
  • NON-CODING
  • Frame 07 / Reconsidered
  • For decades, the 98% of DNA that didn't code for proteins was dismissed as junk. The ENCODE project (2012) and successors have rewritten that story.
  • Regulatory elements — promoters, enhancers, silencers
  • Non-coding RNA — microRNA, lncRNA, structural RNA
  • Transposons — "jumping genes" (~45% of the genome)
  • Evolutionary playground — raw material for new genes
  • ■ Protein-coding 2%
  • ■ Regulatory ~8%
  • ■ Introns ~25%
  • ■ Repetitive / transposons ~50%
  • ■ Other / unknown ~15%
Slide 08

Mutations: the source code of variation

  • 08 / FRAME
  • VARIATION
  • Frame 08 / Errors as Fuel
  • Copy-machine errors in DNA replication generate the raw material for evolution — and most disease. Three flavors:
  • Point mutation
  • One base swapped for another. Sickle cell: a single A→T changes one amino acid in hemoglobin.
  • GAG → GTG
  • Frameshift
  • Insertion or deletion shifts the reading frame — every codon downstream changes. Often catastrophic.
  • ATG CAT GAT
  • ↓ ins A
  • ATG ACA TGA
  • Copy-number
  • Whole sections duplicated or deleted. Down syndrome: a third copy of chromosome 21.
  • [gene] × 1
  • [gene][gene] × 2
  • [gene][gene][gene] × 3
Slide 09

PCR: the photocopier of biology

  • 09 / FRAME
  • 1983 — MULLIS
  • Frame 09 / Amplification
  • Driving on Highway 128 in 1983, Kary Mullis sketched a chain reaction that would double DNA every cycle. Thirty cycles → a billion copies of any chosen sequence.
  • Denature at 95°C — strands separate
  • Anneal at 55°C — primers bind targets
  • Extend at 72°C — Taq polymerase copies
  • From forensics to COVID tests — every modern lab depends on it
  • Electrophoresis Gel
  • L1L2L3L4L5L6
Slide 10

Reading DNA: 100,000× cheaper

  • 10 / FRAME
  • READ-OUT
  • Frame 10 / Sequencing
  • Three generations of technology compressed the cost of a human genome from billions to hundreds of dollars in two decades.
  • 1977 — SANGER
  • Chain-termination method. Read length ~1 kb. Powered the Human Genome Project. ~$1/base.
  • 2005 — ILLUMINA / NGS
  • Massively parallel short-read sequencing. Billions of reads per run. $1000 genome by ~2014.
  • 2015 — NANOPORE / LONG-READ
  • Oxford Nanopore: thread DNA through a protein pore, read electrical signals. Pocket-sized. Reads of 100kb+. ~$200 genome today.
Slide 11

CRISPR-Cas9 programmable editing

  • 11 / FRAME
  • 2012 — DOUDNA / CHARPENTIER
  • Frame 11 / The Edit
  • Borrowed from a bacterial immune system: a guide RNA escorts the Cas9 enzyme to a precise location in the genome, where it cuts. Cellular repair finishes the edit.
  • 2012 — Doudna & Charpentier reprogram Cas9 in a test tube
  • 2020 — Nobel Prize in Chemistry
  • 2023 — Casgevy: first FDA-approved CRISPR therapy (sickle cell)
  • From decades of work to days of design
Slide 12

The programmable body

  • 12 / FRAME
  • FRONTIER
  • Frame 12 / What's Next
  • Editing went from cutting (CRISPR) to rewriting (base editing) to drafting (prime editing). Genetic medicine is moving from theory to clinic.
  • Gene therapies
  • One-time treatments for hemophilia, retinal blindness, spinal muscular atrophy. AAV viral vectors deliver corrected genes directly to target cells.
  • Base & prime editing
  • Rewrite single letters without cutting both strands. Prime editing (Liu, 2019) handles ~89% of known disease-causing mutations.
  • Personalized medicine
  • Pharmacogenomics tailors drugs to your variants. mRNA vaccines designed in days. Cancer immunotherapies engineered patient by patient.
  • Ancestry & populations
  • 23andMe-class consumer kits, ancient DNA from 400,000-year-old bones, the rewriting of human prehistory through genomes.
  • Synthetic biology
  • Designing organisms from scratch. Minimal genomes (Mycoplasma JCVI-syn3.0). Engineered yeast that brews insulin, spider silk, vaccine adjuvants.
  • Open questions
  • Germline editing ethics. Off-target effects. Equity of access. What does it mean to "fix" a genome?
Slide 13

References & further reading

  • 13 / END FRAME
  • 3'-STOP-5'
  • // END OF SEQUENCE
  • YouTube — CRISPR gene editing
  • YouTube — Double helix · Watson & Crick
  • Nature Education — Discovery of DNA structure
  • NIH — Human Genome Project archives
  • Nobel 2020 — CRISPR (Doudna · Charpentier)
  • // FIN — A · T · G · C
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