Genetics 2581: Genes, Genome, and the Tree of Life

Module 1: Genes, Genome, and the Tree of Life

Learning Outcomes

1. Define gene, genome, and allele, and differentiate between genes/alleles.
2. Analyze genome sequence variation and infer transmission.
3. Identify major events in the three-domain representation of the history of life.
4. Identify steps involved in the genesis of eukaryotic organelles.
5. Count the number of genomes at various stages of endosymbiosis.

1.1 Introduction

• Genetics: Study of genome sequence variation.
• Genome: Complete set of inherited instructions contributing to organism traits.
• Gene: Unit of inheritance, specific DNA locus transcribed into RNA.
  • Includes protein-coding genes, introns, tRNAs, and entire DNA sequence for RNA transcription.
• Allele: Variations in specific DNA sequences, causing mutations through interaction with genetic background/environment.

1.2 Genome Sequence Variation

• DNA is chemically inert, storing information while proteins perform major 'chemistry'.
• Genomes are unstable; sequence changes occur due to replication mistakes.
• In a growing genome population without selection pressure, allele count increases per generation (e.g., RNA virus COVID-19).
• Divergence in human genome helps trace ancestry.
• Case Study: NYC COVID-19 infections traced to Europe through sequence variation.
• Coelacanth example: Living organisms are extant species, not 'living fossils'.
• Inheritance & Tree of Life: Nuclear vs. cytoplasmic inheritance, temporal history through the 'tree of life'.
• Protein vs. RNA vs. DNA World: RNA world hypothesized as progenitor of life due to catalytic and information-storing abilities.

1.3 Origin of Eukaryotic Genomes

• Synthetic Biology: Creation/redesign of biological systems.
• Endosymbiosis: Eukaryotic genomes arose from endosymbiotic events (e.g., mitochondria origin).
  • Five steps: Phagocytosis, Symbiosis, Sharing, Entrapment, Gene transfer.
• Genetic Merger: Eukaryotic genomes contain bacterial, archaeal, and novel genes.
• Plant & Algal Genomes: Result from additional endosymbiotic events (e.g., cyanobacteria becoming chloroplasts).

1.4 Supplementary Readings

• Gene Complexity: Genes have complex structures, with findings from Crick on collinearity and experimental evidence.
• Gene Organization: Collinearity proportionality between nucleotides and amino acids.
• Gene Concept: Revisited definitions include noncoding RNAs and transcription units.

Module 2: Exploring the Genome

Learning Outcomes

1. Assess the information content of a DNA sequence.
2. Compare the properties of four major DNA sequencing methods.
3. Identify challenges in assembling a complete genome sequence.
4. Apply the concept of paired-end reads to constructing a scaffold.
5. Identify DNA sequence variations using a reference genome assembly.

2.1 DNA as Information

• Determining sequence uniqueness, information content, and BLAST search usage.
• Information Theory: Base pairs as physical units and bits as informational units.
• BLAST Tool: Identifies sequence similarities, utilizing GenBank database.

2.2 Methods of DNA Sequencing

• Comparison of four sequencing methods: Sanger, Illumina (Next Gen), PacBio, and Nanopore.
• Sanger Sequencing: Chain termination, highly accurate for small regions.
• Illumina: Sequence by synthesis, high throughput, short read lengths, cyclic process.
• PacBio: Single molecule real-time (SMRT), efficient for complex regions.
• Nanopore: Direct RNA sequencing with current change detection.

2.3 Contigs and Gaps

• Contigs: Assembling a larger sequence from small stretches of DNA.
• Sequence Gaps: Poisson distribution, repetitive sequences causing assembly challenges.

2.4 Scaffolding and Reference Genomes

• Scaffold: Ordered contigs with remaining gaps assembled using paired-end reads.
• Long Read Sequencing: Assists in covering repetitive regions.
• Reference Genomes: Used for rapid assembly and identifying sequence variations.

More Modules

The document includes various modules on advanced topics such as genome annotation, origin of genome sequence variation, allele classification, regulation of gene expression, genetics screens, making mutants, epigenetics, chromosomal mutants, and sex determination and behavioral genetics. Each module has detailed breakdowns of mechanisms, experimental studies, and case studies to enhance comprehension of genetic principles.

Summary

The document covers detailed genetic concepts from foundational definitions to complex mechanisms like endosymbiosis, DNA sequencing methods, and evolutionary genetics. Each module clearly outlines specific learning outcomes and explores genetics through theoretical concepts, practical applications, and real-world examples. This structured approach facilitates understanding and retention of genetic principles, making it an essential resource for genetics studies.