🧬 Lecture 1

Survivors of Evolution

• Organisms are programmed to constantly diversify genetically

• Helpful selection removes deleterious alleles

• Balance of diversification + selection → improved fitness in changing, competitive environments

Fitness

• Diversification + vulnerability to helpful selection

• Ability of organism, population, or species to survive, find mate, produce offspring in environment

• e.g. Covid

  • Persistence due to constant new genetic variants

  • Shows power of diversification

  • If tiny virus can do this → imagine power of plants or animals with constant diversification

Primordial Soup

• 3.8 B years ago

• No O₂ (oxygen came from plants)

• High in carbon, nitrogen, sulfur, inorganic phosphorus (PO₄³⁻)

• Heat energy, H₂O present

What is Life?

• Empiricial/functional definition: Programmed series of biochemical reactions that build complex structures from simple elements + molecules (e.g. CO2, N2 gas in the atmosphere, phosphorus, sulfur, H2O, etc.)

  • Facilitated by enzymes, each encoded by a gene

What’s Needed for Chemical Reactions to be Efficient

• Rxns need to be contained within semi-permeable membrane (H₂O and molecules within can’t pass through)

  • Hydrophobic (lipid/fat) cell membrane

  • Key reason why organisms need to build + consume fats/oils

What Else is Needed for Chemical Rxns to be Efficient - Enzymes

• Key to all life on Earth

  • Hydrophobic on outside

• Without enzymes: 2 reactive molecules rely on random diffusion to “find” each other

• With enzymes: Active site binds both molecules, holds them close, allows rxn to occur

What Encodes an Enzyme?

Genes (segments of DNA)

What is the Function of a Gene?

To encode an enzyme + other proteins

Minimal # of Unique Genes Required to Make Multicellular Life

• 11k to 15k

  • Humans have ~21k genes

  • Corn has ~40k genes

Do Genes Float Around in a Cell Freely?

No, they’re in the nucleus

Consequence of Free-Floating Genes After Cell Division

• Genes wouldn’t be distributed equally

• Daughter cells would lose genetic information

• Life would not be sustainable

How Did Evolution Solve This?

• Genes are organized into chromosomes

• Chromsomes ensure accurate replication + segregation during cell divison

Chromosome Structure

• DNA-based genes linked together in long, wound-up “string”

• DNA wraps around histones to form nucleosomes for structural support

• DNA becomes highly compacted (multi-folded) to fit inside nucleus

DNA Length (Outstretched)

• 205 cm in males

• 208 cm for females

Mitosis

• Type of cell division used by higher organisms

• Ensures both resulting cells receive all genes

• Chromosomes of daughter cells are same # as that of founder cell

Asexual Plant Propogation

• Plants from cuttings regenerate by mitosis (genetically identical to parent)

  • Advantage: Maintains desirable traits

  • Disadvantage: No genetics variation (less adaptability)

• Plants are propagated vegetatively/asexually by taking cuttings and placing them in water/soil/ cutting off the top (ratooning)

• e.g. Sugarcane regenerates asexually from ratoon (cut stem)

  • Ornamental plants regenerate from cuttings

  • Potatoes regenerate from tuber pieces

DNA Replication + Mutation

• Inherently makes mistakes (since it has multiple mechanisms), making new alleles

• Every mitosis carries risk of mutation

• Temp effect: Every 10 °C increase → mutation rate rises 2–3 times → potential link to climate change

• Byproducts of cell metabolism (normal growth, G₁, S, G₂) can also mutate

UV Radiation + DNA

• UV radiation > 260 nm is strongly absorbed by nucleotide bases

• Absorption can result in mutations

Mobile Elements and Insertional Mutations

• Mobile elements (jumping genes, mobile DNA, selfish DNA) create insertional mutations in host chromosomes

• Intracellular parasites that insert into genes and cause mutations

• Include: Transposon, retroelements, retroviruses (e.g. HIV), interspersed elements

• Can exist in dozens to millions of copies in higher organisms

Chemical Mutagens

1. Polycyclic Aromatic Hydrocarbons (PAHs)

• From burning natural/industrial materials (e.g. forest fires, refineries, vehicle exhaust)

2. Nitrosamines

• From tobacco, smoked meats/fish, nitrite preservatives in food

3. Alkaloids from Plants

• Natural compounds

4. Benzene

• Industrial solvent and precursor for drugs, plastics, synthetic rubber, dyes

5. Alcohol

6. Fungal Mycotoxins

• In infected foods

Types of Mutations (IDRIS)

• Insertions

  • Adds extra bases

  • e.g. CAGTAG → CATGTAG

• Deletions

  • Removes bases

  • e.g. CAGTAG → CATAG

• Substitutions

  • Replaces base with another

  • e.g. CAGTAG → CAATAG

• Inversion

  • Reverses bases

  • e.g. CAGTAG → GATGAC

• Repeat Expansions

  • Copy same base sequence multiple times

  • e.g. CGGCGGCGG → CGGCGGCGGCGGCGGCGG

Alleles

• Allele: Variant of gene caused by small mutations

• Therefore, all genes come from earlier genes

Dominance + Recessiveness

• Both alleles may encode proteins

• e.g. Brown (B) vs. blue (b) eye color

• Gene encoding protein that “does the job stronger” (e.g. produces more of the protein necessary) is dominant

  • e.g. Allele B: functional protein → brown eye pigment, masks blue

    • Allele b: no protein or little protein → blue eye pigment

• Most alleles are codominant (both proteins contribute to function) or incompletely dominant

  • e.g. Flower colors, coat colors

Spontaneous Mutations and Diversification

• Spontaneous mutations that produce new alleles are major engine of life’s diversification

  • Can have dramatic impacts (e.g. Covid variants)

• Multiple alleles (genetic variants) can exist for a single gene within a population

  • e.g. Blue, brown, green eyes

• Mutations from thousands or millions of years ago can persist and help trace shared ancestry (pedigrees)

• Mutations can eventually produce entirely new genes and enzymes

  • All genes derive from earlier genes → all life on Earth is related, sharing common ancestors

Sex and Genetic Diversity

• Sex introduces genetic diversity from two individuals

• In most higher organisms:

  • Each gene (locus) has a maternal allele and a paternal allele

• Heterozygous: Two different alleles at a gene

• Homozygous: Identical alleles at a gene (used in inbred crops or purebred animals)

• Natural selection favors sex to create genetic diversity with redundancy

• Redundancy (having two copies of an allele that have the same purpose, e.g. eye color) allows safe allelic experimentation in case one allele is harmful/nonfunctional/mutated negatively, the other can still “do the job”

• Additional Terms

  • Sister chromatids: Two identical copies of a single chromosome 

    • Formed during DNA replication

    • Joined at centromere

  • Homologous chromosomes

    • Pair of chromosomes (one maternal, one paternal)

    • Contain same genes but may have different alleles

    • Separate during meiosis to increase genetic diversity

• Simple early life was haploid (could easily replicate by mitosis, no meiosis, no need for mate)

  • Only one copy of each chromosome, only 1 allele at each gene

Haploid Parental Gametes

• Each parent contributes one haploid (n) gamete (one copy of each chromosome)

• Female × Male → F1 (1st filial generation)

  • By convention, female parent is listed first in a genetic cross

Utility of Two Alleles at a Gene After Sex

• Creates genetic diversity within a generation → May be beneficial

• Enzymes encoded by genes can affect multiple traits or multiple stages

• A novel allele might improve one trait/stage but harm another

• Redundant chromosome from sex allows:

  • Safe experimentation with novel alleles

  • Retention of beneficial alleles in population

  • Promotion of long-term diversity (critical concept)

Utility of Two Alleles at a Gene

• In a haploid, slightly deleterious (bad) or neutral alleles:

  • Likely eliminated quickly or drift out slowly

  • Limits genetic diversification → Organism stays simple

• Experimental sex provides safe allelic experimentation

• In higher plants and animals, diploid/polyploid “safe space”:

  • Needed to unleash full diversification potential of meiosis

  • Meiosis occurs before sex

Summary

1. Life is a programmed series of biochemical rxns, facilitated by enzymes, each encoded by a gene

2. To facilitate reproducible transmission to daughter cells, genes are linked together to form chromosomes

3. Chromosomes replicate to facilitate multicellularity and simple replication (e.g. mitosis)

4. DNA replication, parasites, and mutagens cause mutations (new alleles)

5. Natural selection favors sex to create genetic diversity with redundancy, permitting safe allelic experimentation

Reading 1: George Beadle: From Genes to Proteins

• Early life: Born in 1903, grew up on a farm in Wahoo, Nebraska; originally interested in farming, shifted to genetics in college

• Education and mentors: Studied at University of Nebraska (College of Agriculture) and Cornell University; influenced by F. D. Keim and Rollins Emerson; gained early experience with maize genetics

• Caltech and Drosophila: Postdoctoral work at Caltech with Thomas Hunt Morgan’s Fly Group (Sturtevant, Bridges, Dobzhansky, Schultz); mastered Drosophila genetics, crossing-over, and chromosome behavior

• Early research: Worked with Boris Ephrussi on eye-color mutations in Drosophila; demonstrated genes control specific steps in metabolic pathways (vermilion → kynurenine, cinnabar → 3-hydroxykynurenine)

• Insight from Tatum: Inspired by Edward Tatum’s lecture on genes and metabolic function; led to experiments linking genes to enzyme production

• Neurospora crassa experiments: Induced mutations using radiation; identified nutritional mutants with single-gene defects; established the one gene–one enzyme hypothesis

• One gene–one enzyme legacy: Evolved into one gene–one protein → one gene–one polypeptide; modern understanding includes noncoding regions, alternative splicing, and genes encoding RNA

• Scientific impact: Introduced a paradigm for mutational analysis to dissect metabolic pathways; influenced identification of genes, enzymes, and regulatory mechanisms (e.g., tryptophan in E. coli, histidine in Salmonella)

• Leadership and advocacy: Chaired NRC panel on radiation fallout; defended scientific integrity during McCarthy era; emphasized mentorship and collaborative research environment

• Key contributions:

• Showed genes direct production of proteins

• Demonstrated sequential steps in metabolic pathways are gene-controlled

• Pioneered experimental approaches linking genetics to biochemistry

• Provided foundation for molecular biology and modern genetics

• Mutagenesis paradigm in complex processes

• Purpose: Uses mutations to analyze complex physiological processes in eukaryotes

• Applications:

  • Cell cycle regulation (yeast)

  • Embryonic development (Drosophila)

  • Memory and learning

  • Vision and olfaction

  • Aging and lifespan regulation

• Key examples:

  • Yeast cell cycle mutants identify regulatory proteins controlling specific stages

  • Edward B. Lewis: Drosophila body plan mutants

  • Christiane Nüsslein-Volhard: Early developmental step mutations in Drosophila

  • Lifespan and learning genes identified via mutagenesis in model organisms

• Techniques:

  • Tagging or insertional mutagenesis

  • Allows gene cloning, structural analysis, protein identification, and functional study

• Takeaway: Mutagenesis reveals how discrete genes control sequential and complex biological processes

Reading 2: Barbara McClintock

• Early life and education

  • Mother opposed higher education; father supported

  • Graduated early from Erasmus Hall High School

  • Enrolled Cornell University in 1919, focused on plant genetics

• Research and contributions

  • Studied chromosome structure and cytogenetics in maize

  • First genetic map of maize (1931) – order of 3 genes on one chromosome

  • Discovered recombination correlated with new traits

  • Investigated unstable inheritance and mosaicism in maize

  • Introduced concept of “controlling elements” (jumping genes)

• Career and challenges

  • Assistant professor at University of Missouri (1941); faced gender discrimination

  • Joined Carnegie Institution/Cold Spring Harbor (CSHL) in 1941; gained freedom to pursue research

  • Helped design Department of Genetics at CSHL post-WWII

  • Mentored future scientists, e.g., Robert Martienssen

• Recognition

  • First woman awarded National Medal of Science (1970)

  • Continued research on genome changes and transposable elements

  • Nobel Prize lecture (1983) highlighted genome’s response to unexpected stimuli

• Legacy

  • Pioneered plant cytogenetics and transposable element research

  • Established CSHL as major genetics research hub

  • Inspired new generations of geneticists and epigenetics researchers