Foundations of Genetics: Heredity, DNA Structure, and Gene Expression

GENETICS: Introduction

Definition and Scope

Genetics is the scientific study of heredity and variation in living organisms. It explores how traits are passed from one generation to the next and how genetic differences arise.

• Gene: A unit of heredity, consisting of a discrete segment of DNA that encodes information for a specific trait.

• Variation: Differences in genetic makeup among individuals within a population.

Historical Concepts

• Homunculus: An early concept depicting a preformed human within sperm, reflecting preformation theory.

Genetics: Timeline

Early Theories of Heredity

• Prehistoric Times: Recognition of heredity's existence.

• Hippocrates (460–370 B.C.): Proposed that hereditary traits are formed by all body cells and collected in reproductive organs (Pangenesis theory).

• Aristotle (384–322 B.C.): Suggested traits are formed from blood containing "vital heat," which shapes physical substance when mixed with menstrual blood.

• Paracelsus (1493–1591): Introduced the theory of preformation (Homunculus).

• William Harvey (1578–1657): Contradicted preformation, asserting the ex ovo omnia principle—all animals come from eggs.

• Casper Wolff (1733–1794): Coined the theory of epigenesis—organisms develop from substances in the egg.

Development of Modern Genetics

• Joseph Kölreuter (1733–1806): Studied genetic crosses in plants, supporting the blending theory of inheritance.

• Gregor Mendel (1856–1863): Discovered inheritance patterns in pea plants, founding Mendelian genetics.

• Charles Darwin (1859): Published "The Origin of Species," introducing descent with modification and natural selection.

• Alfred Russell Wallace (1855): Independently proposed natural selection.

• Hugo de Vries, Carl Correns, Erich von Tschermak (1900): Verified Mendel's experiments.

• Schleiden and Schwann (1830): Formulated the cell theory—all organisms are composed of cells.

• Nettie Stevens and Edmund Wilson (1905): Studied sex chromosomes.

• Thomas Hunt Morgan (1910): Developed the theory of sex-linked inheritance.

What is the Hereditary Material?

Biochemical Foundations

Cells are constructed from small organic molecules linked by chemical bonds to form larger molecules. Four main types of large molecules are found in cells:

• Carbohydrates: Energy storage molecules.

• Lipids: Form membranes and serve as energy storage.

• Proteins: Biochemical functions and phenotype determination.

• Nucleic acids: DNA and RNA, the genetic material of cells.

Hershey-Chase Experiment

Demonstrating DNA as Genetic Material

The Hershey-Chase experiment used bacteriophages labeled with radioactive isotopes to show that DNA, not protein, is the hereditary material transferred to bacteria during infection.

• Protein coat labeled with 35S: Radioactivity found in the medium.

• DNA labeled with 32P: Radioactivity found in bacterial cells.

Why is DNA the Genetic Material?

Properties of DNA

• All known living organisms have genes made of DNA.

• DNA is used to transcribe RNA and translate proteins.

• DNA is less abundant and less variable than protein.

• DNA can replicate; proteins cannot (except prions).

• DNA is structurally and chemically stable.

• DNA allows for mutation, essential for evolution.

DNA: The Hereditary Material

Discovery and Structure

• Friedrich Miescher (1869): First identified DNA.

• DNA is an antiparallel, double-stranded helix.

DNA Monomer: A Nucleotide

Nucleotide Structure

• Phosphate group

• Sugar: Deoxyribose (DNA) or ribose (RNA)

• Nitrogenous base: Adenine, cytosine, guanine, or thymine (uracil in RNA)

• Sugar, base, and phosphate are covalently linked.

Bases Classification

• Purines: Adenine and Guanine

• Pyrimidines: Thymine and Cytosine (Uracil in RNA)

DNA: The Antiparallel, Double-Strand Helix

Structural Features

• Two linear strands of covalently linked nucleotides.

• Strands oriented in opposite directions (3'→5' and 5'→3').

• Strands linked by hydrogen bonds (complementary base pairing).

• Chargaff's Rule: A=T and G=C.

Key Discoveries

• Rosalind Franklin: Photographed DNA double helix (Photo 51).

• Watson and Crick: Built DNA model using Franklin's data; published in 1953.

The Central Dogma of Molecular Biology

Flow of Genetic Information

Genetic information flows from DNA to RNA to protein.

• Gene: Discrete unit of heredity within DNA.

• Allele: Alternate form of a gene due to mutation.

• Genotype: Collection of genes or genetic constitution.

• Phenotype: Observable characteristics resulting from genotype and environment.

Relationship Between Genetic Material and Phenotypic Trait

Gene-Protein-Trait Connection

• A gene encodes a polypeptide chain.

• Protein activity results in a trait or characteristic.

Basic Gene Structure

Gene Organization

• Genes are located on chromosomes within the nucleus.

• Gene structure includes promoter, transcription start site, coding sequence, and transcription stop site.

Activation of a Gene Promoter

Transcription Factors and Promoter Recognition

• Transcription factors and activators bind to enhancers and promoter regions to initiate transcription.

• Promoter recognition sequences include GC box, CAAT box, and TATA box.

Transcribed Region

• Regulatory regions (enhancer, promoter, TATA box) control gene expression.

• Transcribed region includes exons (coding) and introns (non-coding).

Transcription Initiation

Process Overview

• RNA polymerase binds to promoter and initiates transcription.

• Transcription bubble forms as DNA unwinds and RNA is synthesized.

Coding versus Template Strand in DNA

Transcription Bubble

• RNA polymerase reads the template strand (3'→5') and synthesizes RNA (5'→3').

• New nucleotides are added to the 3' end of the growing RNA molecule.

The Pre-mRNA Structure

Components

• 5' Untranslatable Region (UTR): Leader sequence, ribosome binding site, protects mRNA, site for 5' cap addition.

• Exons and Introns: Exons are coding regions; introns are non-coding and removed by splicing.

• 3' Untranslated Region (UTR): Trailer sequence, bears stop codon, site for poly-A tail addition, regulates mRNA processes.

Post-Transcriptional Modifications

Splicing of Introns

• Introns are removed from pre-mRNA by the spliceosome, resulting in mature mRNA.

Addition of 5' Cap and Poly-A Tail

• 5' Cap: Regulates nuclear export, prevents degradation, promotes translation.

• Poly-A Tail: Added during RNA processing, stabilizes mRNA, prevents degradation, facilitates export and translation.

DNA Stores the Information for Protein Synthesis

Triplet Code

• Genetic code consists of three DNA bases (triplet code).

• Each triplet (codon) encodes a specific amino acid.

In RNA the Triplet is called a Codon

Translation Process

• The coding sequence includes a start codon (AUG for methionine) and a stop codon (does not encode an amino acid).

RNA Codons of the Universal Genetic Code

Codon Table and Special Amino Acids

• Universal genetic code encodes 20 of the 22 amino acids.

• Methionine and Tryptophan are encoded by a single RNA codon.

• UAA, UAG, UGA are stop codons.

• Selenocysteine and pyrrolysine are the 21st and 22nd amino acids, incorporated by unique mechanisms.

Codon	Amino Acid
AUG	Methionine (Start)
UAA, UAG, UGA	Stop
UGA	Selenocysteine (Sec)
UAG	Pyrrolysine (Pyl)
Others	Standard amino acids

Selenocysteine and Pyrrolysine

Special Amino Acids

• Selenocysteine (Sec): Encoded by UGA, found in selenoproteins, important for antioxidant function.

• Pyrrolysine (Pyl): Encoded by UAG, found in certain archaea, important in methane production.

Sample Question

Calculating Amino Acids from a DNA Sequence

Given a DNA sequence of 561 nucleotides, with the first three as thymine, adenine, cytosine (TAC) and the last three as adenine, thymine, cytosine (ATC):

• TAC is the start codon (encodes methionine).

• ATC is transcribed to UAG (stop codon, not translated).

• Translatable nucleotides: 561 - 3 = 558

• Number of translated codons: $558 \div 3 = 186$

Additional info:

• These notes cover foundational topics in genetics, including the history, molecular basis, and mechanisms of gene expression, relevant to college-level genetics courses.