Genetics: Introduction, Genome Structure, and Mendelian Inheritance

Course Introduction

Overview of Genetics

Genetics is the scientific study of heredity and variation in living organisms. It explores how genetic information is stored, transmitted, and expressed, forming the basis for understanding biological diversity and inheritance.

• Genome: The complete set of genetic material in an organism.

• Applications: Medicine, agriculture, evolutionary biology, and biotechnology.

The Central Dogma and Molecular Genetics

Flow of Genetic Information

The central dogma describes the flow of genetic information from DNA to RNA to protein, outlining the molecular basis of gene expression.

• Replication: DNA makes copies of itself.

• Transcription: DNA is transcribed into RNA.

• Translation: RNA is translated into protein.

• Gene Regulation: Ensures the right products are made at the right time and place.

Genetics is the Study of the Genome

Definition and Structure

The genome encompasses all genetic information within an organism, typically in the form of DNA (or RNA in some viruses).

• Physical Forms:

  • Most organisms: double-stranded DNA (dsDNA)

  • Some viruses: single-stranded DNA (ssDNA), single-stranded RNA (ssRNA), double-stranded RNA (dsRNA)

• Functional Elements: Genes, enhancers, insulators, telomeres, transposons

• Genes: DNA sequences that specify RNAs (non-coding) or proteins (coding)

Where Does the Genome Live?

Cellular Localization

Genetic material is housed in specific cellular compartments depending on the organism type.

• Prokaryotes: Genome resides in the cytoplasm, typically as a single circular chromosome or plasmid.

• Eukaryotes: Genome is found in the nucleus (chromosomes), mitochondria, and chloroplasts (plants).

The Genome is Packed into a Chromosome

Chromosome Structure

Chromosomes are highly organized structures that package DNA with proteins, facilitating its function and inheritance.

• Eukaryotes:

  • Each chromosome is a complex of a single DNA molecule and packaging proteins (e.g., histones).

  • Organisms may have multiple chromosomes.

• Prokaryotes and Organelles:

  • DNA is packaged as circular plasmids.

  • Plasmids can carry many genes; some bacteria have multiple plasmids.

Basic Packaging of Chromosomes

Comparison of Prokaryotic and Eukaryotic Chromosomes

• Prokaryotic Cell: DNA is circular and attached to the cell membrane.

• Eukaryotic Cell: DNA is linear, organized into chromosomes, and wrapped around histone proteins within the nucleus.

Genome as a Set of Recipes

Analogy for Understanding

Think of the genome as a set of recipes for building and maintaining an organism.

• Chromosome: Like a book or volume in a set.

• Gene: Like a recipe for one protein or RNA.

• Prokaryotes: One circular plasmid = one chromosome.

• Eukaryotes: Multiple linear DNA molecules; humans have 23 pairs of chromosomes with 2000–3000 genes per chromosome.

Chromosomes Contain Genes

Gene Organization

• Chromosomes are composed of DNA and packaging proteins.

• Genes can code for proteins or non-coding RNAs.

• In higher organisms, coding genes are a small portion of the genome; the rest consists of non-gene elements.

Coding Genes are Only a Small Portion of the Genome in Complex Organisms

Human Genome Example

• Human coding genes constitute about 1% of the genome (20,000–25,000 genes).

• The majority of the genome consists of non-coding regions and regulatory elements.

Ploidy Affects Trait Inheritance Patterns

Chromosome Sets and Their Impact

Ploidy refers to the number of complete sets of chromosomes in a cell, influencing inheritance and genetic diversity.

• Diploid (2n): Two sets of chromosomes (maternal and paternal); most animal cells.

• Monoploid (1n): One set; found in certain species (bacteria, male bees) or life cycle stages (yeast, algae).

• Haploid: Gametes (egg and sperm) contain half the chromosome number of zygotes.

Polyploidy in Organisms and Cells

Multiple Chromosome Sets

• Polyploid: More than two sets of chromosomes; common in plants, some insects, fish, and amphibians.

• Polyploidy in birds and mammals is often fatal, but normal in certain tissues (muscle, liver, placenta).

• Associated with genome instability in cancers.

Homologous Chromosomes

Definition and Importance

• In diploid organisms, homologous chromosomes are pairs with the same genes in the same order, one from each parent.

• Sequences may be similar but not identical.

Cells Contain Nuclei that House Pairs of Chromosomes

Genetic Analysis

• Genetic analysis studies how changes in DNA (genotype) lead to changes in observable traits (phenotype).

Traits: Definition and Types

Observable Characteristics

• Traits: Outward appearance, behavior, development, metabolism, disease susceptibility.

• Simple Traits: Controlled by a single gene.

• Complex Traits: Controlled by multiple genes (e.g., height, intelligence).

• Pleiotropic Traits: One gene affects multiple traits (e.g., sickle-cell hemoglobin gene).

Genotype Versus Phenotype

Key Distinctions

• Genotype: Genetic makeup; specific mutations in genes.

• Phenotype: Observable manifestation of traits (e.g., eye color).

• Complex traits can result from mutations in different genes within the same pathway.

Relating Phenotype to Genotype for Complex Traits

Pathway Analysis

• Mutations in different enzymes of a metabolic pathway can produce similar phenotypes.

Example pathway:

• Metabolite A --(Enzyme 1)--> B --(Enzyme 2)--> C --(Enzyme 3)--> D

Mutation in Enzyme 1 or Enzyme 3 may result in similar phenotypic outcomes.

Traits are Influenced by Environmental Factors

Nature vs. Nurture

• Same genotype does not always produce the same phenotype due to environmental influences.

• Experiments with genetically identical organisms in different environments can reveal the degree of genetic contribution.

Alleles of Genes Determine Genotype

Allelic Variation and Mutation

• Allele: Variant form of a gene due to mutations.

• Types of mutations:

  • Small changes in DNA sequence

  • Partial or complete gene deletion/duplication

• Sources:

  • Mutagens (UV light, chemicals)

  • Replication errors (higher in viruses and lower organisms)

COVID-19 Variants: Mutation Example

Viral Mutation Dynamics

• Viruses mutate rapidly due to low replication fidelity.

• Dominant variants arise from advantageous mutations, leading to further diversification.

Gregor Mendel's Experiments

Foundations of Classical Genetics

• Mendel studied inheritance in pea plants, focusing on seven traits.

• Each trait was controlled by a single gene with two alleles (dominant and recessive).

• Formulated two fundamental laws:

  • Law of Segregation: Alleles of one gene segregate in a 3:1 ratio.

  • Law of Independent Assortment: Alleles of different genes assort independently, producing a 9:3:3:1 ratio.

Why Do Traits Sometimes "Skip a Generation"?

Particulate Inheritance

• Traits are not blended but remain particulate.

• Two copies in adults, one in gametes; fusion at fertilization restores pairs.

• Example: Tall plants have a gene (T) encoding a protein for gibberellic acid response.

Alleles Can Arise from Any Part of a Gene

Gene Structure and Mutation

• Gene = regulatory sequences + coding sequences.

• Regulatory sequences:

  • Promoter, enhancer, terminator (bacteria)

  • Untranslated regions (UTR)

  • Introns (eukaryotes)

• Mutations in any region can produce different alleles.

Populations Contain Many Alleles

Genetic Diversity

• Populations can have multiple alleles for a gene (e.g., ABO blood types).

• Diploid individuals carry two alleles:

  • Homozygous: two identical alleles

  • Heterozygous: two different alleles

• Both alleles interact to determine phenotype.

Not All Alleles Are Created Equally

Functional Consequences

• Different alleles may or may not produce the same phenotype.

• Phenotype depends on protein quantity and function.

• Categories:

  • Wild type, gain of function, loss of function

  • Dominant, recessive

  • Interaction types (Muller's morphs)

Both Alleles Interact to Control a Trait

Gene Activity and Phenotype

• Changes in DNA sequence affect protein activity, influencing phenotype.

• Types of allelic effects:

  • Wild type: fully functional

  • Loss of function: partial or complete

  • Gain of function: more, ectopic, better, or new function

Misconceptions and Why They Are Wrong

Clarifying Genetic Principles

• Mutations are all bad: Most are neutral, especially in large genomes.

• Mutations give rise to superpowers: Most are neutral or loss-of-function.

• Gain-of-function mutations are purposely made: They occur naturally and drive evolution.

• Gain-of-function mutations are always good: Many are detrimental, such as those causing cancer.

Table: Mendel's Pea Plant Traits

Trait	Dominant Allele	Recessive Allele
Seed Shape	Round (R)	Wrinkled (r)
Seed Color	Yellow (Y)	Green (y)
Pod Shape	Inflated (I)	Constricted (i)
Pod Color	Green (G)	Yellow (g)
Flower Color	Purple (P)	White (p)
Flower Position	Axial (A)	Terminal (a)
Stem Length	Tall (T)	Dwarf (t)

Key Equations

• Law of Segregation: $3:1$ phenotypic ratio for a single gene with two alleles.

• Law of Independent Assortment: $9:3:3:1$ phenotypic ratio for two genes with two alleles each.

Additional info:

• Some context and definitions were expanded for clarity and completeness.

• Table entries for Mendel's traits were inferred from standard genetics knowledge.