Genetics: Introduction, Genome Structure, and Mendelian Principles

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 traits and evolution.

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

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

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 processes that underlie 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 Elements of the Genome

The genome encompasses all genetic information within an organism, organized in various physical and functional forms.

• Physical Forms: DNA (most organisms), RNA (some viruses).

• Types of DNA: Double-stranded DNA (dsDNA), 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 of Genetic Material

Genetic material is compartmentalized within cells, varying between prokaryotes and eukaryotes.

• 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.

The Genome is Packed into a Chromosome

Chromosome Structure and Packaging

Chromosomes are highly organized structures that package DNA and associated proteins, facilitating efficient storage and regulation.

• Eukaryotes: Chromosomes are linear DNA molecules complexed with proteins (histones).

• Prokaryotes: Chromosomes are typically circular DNA molecules; plasmids are additional small, circular DNA elements.

Basic Packaging of Chromosomes

Comparison of Prokaryotic and Eukaryotic Chromosomes

Chromosome packaging differs between prokaryotic and eukaryotic cells, affecting gene regulation and stability.

• Prokaryotic Cells: DNA is attached to the cell membrane and forms a nucleoid.

• Eukaryotic Cells: DNA is wrapped around histones, forming chromatin within the nucleus.

Genome as a Set of Recipes

Analogy for Understanding Genome Organization

The genome can be thought of as a set of instructions or 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 equals one chromosome.

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

Chromosomes Contain Genes

Gene Distribution and Non-Coding Elements

Chromosomes are composed of both coding and non-coding regions, with genes representing only a small fraction in complex organisms.

• Coding Genes: Encode proteins or functional RNAs.

• Non-Coding Elements: Regulatory sequences, non-coding RNAs, and other structural components.

Coding Genes are Only a Small Portion of the Genome

Proportion of Coding DNA

In complex organisms, coding genes make up a minor fraction of the total genome.

• Humans: Coding genes constitute about 1% of the genome (20,000–25,000 genes).

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; certain species and life stages (e.g., bacteria, male bees).

• Haploid: Gametes contain half the chromosome number of zygotes.

Polyploidy in Organisms and Cells

Multiple Chromosome Sets

Polyploidy is the condition of having more than two complete sets of chromosomes, common in plants and some animals.

• Plants: Polyploidy is frequent and can result in larger, more robust species (e.g., cultivated strawberries are octoploid).

• Insects: Polytene chromosomes in certain tissues.

• Birds and Mammals: Polyploidy is often fatal but can occur in specific tissues (muscle, liver, placenta).

• Cancers: Associated with genome instability.

Homologous Chromosomes

Definition and Properties

Homologous chromosomes are pairs of chromosomes in diploid organisms, each inherited from one parent.

• Same Genes: Homologs have the same genes in the same order but may differ in sequence.

• Genetic Variation: Differences between homologs contribute to genetic diversity.

Cells Contain Nuclei with Chromosome Pairs

Importance in Genetic Analysis

Studying how changes in DNA sequences (genotype) affect observable traits (phenotype) is central to genetics.

• Genotype: The genetic makeup of an organism.

• Phenotype: The observable characteristics resulting from genotype and environment.

Traits: Definition and Types

Observable Characteristics and Genetic Control

Traits are measurable or observable characteristics influenced by genetic and environmental factors.

• 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

Relationship and Examples

Genotype refers to the genetic constitution, while phenotype is the manifestation of traits.

• Example: Eye color is a trait; blue, brown, green, black are phenotypes; different mutations in the same gene represent different genotypes.

• Complex Traits: Multiple genes and environmental factors can result in similar phenotypes from different genotypes.

Relating Phenotype to Genotype for Complex Traits

Pathways and Mutational Effects

Complex traits often involve multiple genes in a pathway, where mutations in different genes can produce similar phenotypes.

• Example Pathway: $A \xrightarrow{\text{Enzyme 1}} B \xrightarrow{\text{Enzyme 2}} C \xrightarrow{\text{Enzyme 3}} D$ Mutations in Enzyme 1 or Enzyme 3 can both disrupt the pathway, potentially resulting in similar phenotypes.

Traits are Influenced by Environmental Factors

Nature vs. Nurture

Both genetic makeup and environmental conditions contribute to trait expression.

• Nature: Genotype.

• Nurture: Environment and lifestyle.

• Experimental Example: Genetically identical mice raised in different environments can exhibit different phenotypes.

Alleles of Genes Determine Genotype

Allelic Variation and Mutation

Alleles are variant forms of a gene, arising from mutations that can affect gene function and phenotype.

• Types of Mutations: Small changes (point mutations), deletions, duplications.

• Sources: Natural replication errors, mutagens (UV light, chemicals).

• Example: ABO blood types are determined by different alleles of the same gene.

COVID-19 Variants: Mutation and Evolution

Viral Mutation Dynamics

Viruses like SARS-CoV-2 mutate rapidly due to low replication fidelity, leading to the emergence of new variants.

• Dominant Variants: Mutations that confer advantages become prevalent.

• Phylogeny: More mutations result in larger, more complex phylogenetic trees.

Gregor Mendel's Experiments

Foundations of Mendelian Genetics

Gregor Mendel's work with pea plants established the fundamental laws of inheritance.

• Studied: >5000 plants, focused on 7 traits.

• Traits: Each controlled by one gene, with dominant and recessive alleles.

• Laws: Law of Segregation and Law of Independent Assortment.

Why Do Traits Sometimes "Skip a Generation"?

Particulate Inheritance

Traits can reappear in subsequent generations due to the segregation and recombination of alleles.

• Key Points: Genes remain discrete (not blended), two copies in adults, one in gametes, fusion at fertilization.

• Example: Tall plants have a gene (T) encoding a protein involved in growth.

Mendel Studied 7 Traits in Pea Plants

Single-Gene Control and Ratios

Mendel's experiments revealed predictable inheritance patterns for traits controlled by single genes.

• Traits: Seed shape, color, flower color, pod shape, pod color, flower position, stem length.

• Alleles: Each gene had two alleles (dominant and recessive).

• Ratios: $3:1$ for single gene segregation; $9:3:3:1$ for independent assortment of two genes.

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

Alleles Can Arise from Any Part of a Gene

Gene Structure and Mutation Sites

Genes consist of regulatory and coding sequences, and mutations can occur in any region, producing different alleles.

• Regulatory Sequences: Promoters, enhancers, terminators, untranslated regions (UTRs), introns.

• Mutational Effects: Changes in regulation or coding can alter gene function and phenotype.

Populations Contain Many Alleles

Genetic Diversity and Allelic Interactions

Populations exhibit genetic diversity through multiple alleles of a gene, but individuals can only carry two alleles (diploid).

• Homozygous: Two identical alleles.

• Heterozygous: Two different alleles.

• Phenotype Determination: Both alleles interact to produce the phenotype.

Not All Alleles Are Created Equally

Functional Consequences of Allelic Variation

Different alleles may produce different phenotypes depending on changes in protein quantity or function.

• Categories: Wild type, gain of function, loss of function, dominant, recessive.

• Functional Impact: Changes in DNA sequence can affect protein amount, sequence, or function, leading to varied phenotypes.

Both Alleles Interact to Control a Trait

Gene Activity and Phenotypic Outcomes

The interaction between alleles determines the overall activity of a gene and the resulting trait.

• Wild Type: Fully functional allele.

• Loss of Function: Partial or complete loss of activity.

• Gain of Function: Increased, ectopic, or novel activity.

Misconceptions and Why They Are Wrong

Common Myths in Genetics

Several misconceptions exist regarding mutations and their effects.

• 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.