Genetics and Evolution

Molecular Basis of Inheritance

In the absence of lactose

• Introduction to molecular basis of inheritance
• Link between genetics and evolution
• Role of lactose in inheritance

Overview of Genetics and Evolution

• Genetics: The study of genes and heredity
• Evolution: The process by which species change and diversify over time
• The connection between genetics and evolution

Molecular Basis of Inheritance

• DNA (Deoxyribonucleic acid) as the genetic material
• Importance of DNA in inheritance
• Structure of DNA (double helix)

DNA Replication

• Semiconservative replication
• Role of DNA polymerase
• Enzymes involved in DNA replication
• Importance of accurate replication

Transcription

• Process of transferring genetic information from DNA to RNA
• Role of RNA polymerase
• Mechanism of transcription
• Different types of RNA (mRNA, tRNA, rRNA)

Genetic Code and Translation

• Genetic code: The language of nucleotides that determines the sequence of amino acids in proteins
• Codons and anti-codons
• Role of ribosomes in translation

Gene Expression and Regulation

• Gene expression: The process by which information from a gene is used to synthesize a functional gene product
• Transcription factors
• Role of enhancers and promoters
• Regulation of gene expression

Mutations and Genetic Variation

• Mutations: Changes in the DNA sequence
• Types of mutations (point mutations, insertions, deletions)
• Causes of mutations (chemicals, radiation, errors in DNA replication)
• Role of mutations in genetic variation and evolution

Recombinant DNA and Genetic Engineering

• Recombinant DNA technology: Combining DNA from different sources
• Cloning of genes and organisms
• Applications of genetic engineering (insulin production, genetically modified crops)

Inheritance of Genetic Disorders

• Autosomal and sex-linked disorders
• Pedigree analysis
• Genetic counseling
• Pre-implantation genetic diagnosis (PGD)

Introduction to Gene Regulation

• Gene regulation: The control of gene expression in response to internal and external factors
• Importance of gene regulation in maintaining cellular homeostasis
• Examples of gene regulation in development, metabolism, and response to environmental stimuli

Types of Gene Regulation

• Transcriptional regulation: Control of gene expression at the level of transcription
  • Induction and repression of gene expression
  • Transcription factors and enhancers
• Post-transcriptional regulation: Control of gene expression after transcription
  • RNA splicing and alternative splicing
  • RNA stability and degradation

Transcriptional Regulation

• Role of transcription factors in controlling gene expression
  • Activators and repressors
• Promoters and enhancers: DNA sequences that regulate transcription
  • Promoters: Binding sites for RNA polymerase
  • Enhancers: Enhance or suppress transcription through binding of specific transcription factors

Mechanisms of Transcriptional Regulation

• Induction: Activation of gene expression in response to specific signals or stimuli
  • Example: Induction of lac operon in the presence of lactose
• Repression: Inhibition of gene expression in response to specific signals or stimuli
  • Example: Repression of lac operon in the absence of lactose

Lac Operon: Inducible Gene Regulation

• Lac operon in E. coli: A classic example of inducible gene regulation
• Components of the lac operon:
  • Structural genes: lacZ, lacY, lacA
  • Operator: Binds to repressor protein
  • Repressor protein: Prevents transcription in the absence of lactose
  • Promoter: RNA polymerase binding site

Mechanism of Lac Operon Induction

• In the absence of lactose:
  • Repressor protein binds to the operator, blocking RNA polymerase access
  • lac operon is not transcribed
• In the presence of lactose:
  • Lactose is converted to allolactose by β-galactosidase (encoded by lacZ)
  • Allolactose binds to the repressor protein, causing conformational change
  • Repressor protein can no longer bind to the operator, allowing RNA polymerase to initiate transcription of lac operon

Role of cAMP-CRP in Lac Operon Regulation

• cAMP-CRP (cAMP receptor protein): Enhances transcription of the lac operon
• Regulation of cAMP levels:
  • High glucose levels inhibit adenylate cyclase, reducing cAMP levels
  • Low glucose levels stimulate adenylate cyclase, increasing cAMP levels
• In the presence of lactose and low glucose levels, cAMP-CRP complex binds near the lac operon promoter, enhancing transcription

Post-transcriptional Regulation

• Alternative splicing: Different ways of splicing primary RNA transcripts to produce different protein isoforms
  • Example: Alternative splicing of the Dscam gene in Drosophila
• RNA stability and degradation: Control of gene expression by regulating the stability of mRNA molecules
  • Example: microRNAs (miRNAs) that bind to mRNA and promote degradation or inhibit translation

Chromatin Remodeling and Gene Regulation

• Chromatin structure: DNA wrapped around histone proteins
• Chromatin remodeling complexes: Modify chromatin structure to regulate gene expression
  • Example: ATP-dependent chromatin remodelers that slide or evict nucleosomes
• DNA methylation: Addition of methyl groups to DNA that can affect gene expression
  • Example: Methylation of CpG islands in gene promoters can silence gene expression

Summary

• Gene regulation plays a critical role in controlling gene expression in response to internal and external factors
• Transcriptional regulation controls gene expression at the level of transcription, through induction or repression mechanisms
• Lac operon is an example of inducible gene regulation in bacteria
• Post-transcriptional regulation involves alternative splicing, RNA stability, and degradation
• Chromatin remodeling and DNA methylation also contribute to gene regulation in eukaryotes

Types of Genetic Mutations

• Point mutations: Single base changes
  • Silent mutations: No change in the amino acid sequence
  • Missense mutations: Change in the amino acid sequence
  • Nonsense mutations: Introduction of stop codons, leading to premature termination
• Frameshift mutations: Insertions or deletions that disrupt the reading frame
• Chromosomal mutations: Larger-scale changes in chromosome structure or number
  • Deletions, duplications, inversions, translocations

Genetic Disorders

• Autosomal dominant disorders:
  • Huntington’s disease
  • Marfan syndrome
  • Neurofibromatosis
• Autosomal recessive disorders:
  • Cystic fibrosis
  • Sickle cell anemia
  • Tay-Sachs disease
• X-linked disorders:
  • Hemophilia
  • Duchenne muscular dystrophy
  • Color blindness

Genetic Testing

• Methods for genetic testing:
  • Polymerase chain reaction (PCR)
  • DNA sequencing
  • Fluorescence in situ hybridization (FISH)
  • Karyotyping
• Uses of genetic testing:
  • Diagnosis of genetic disorders
  • Carrier screening
  • Prenatal testing
  • Forensic analysis

Population Genetics

• Study of genetic variation within and between populations
• Hardy-Weinberg equilibrium:
  • Describes the relationship between allele frequencies and genotype frequencies in a population
  • Assumptions: large population, no mutation, random mating, no migration, no selection
• Genetic drift: Random changes in allele frequencies due to chance events (bottleneck effect, founder effect)

Evolutionary Mechanisms

• Natural selection: Differential survival and reproduction of individuals based on their heritable traits
  • Adaptive traits increase an individual’s fitness
  • Directional, stabilizing, and disruptive selection
• Gene flow: Movement of genes between populations through migration
• Mutation: Source of new genetic variation
• Genetic drift: Random changes in allele frequencies

Molecular Clocks

• Molecular clocks: Use of genetic mutations to estimate the time of divergence between species
• Rate of mutation: Measured by comparing DNA sequences or protein sequences
• Assumptions: Clock-like accumulation of mutations, constant mutation rate over time and across lineages
• Applications: Estimating evolutionary relationships, dating evolutionary events

Speciation

• Speciation: Process by which one species splits into two or more distinct species
• Allopatric speciation: Geographical isolation leads to reproductive isolation
• Sympatric speciation: Speciation occurs without geographical isolation, often due to polyploidy or habitat differentiation
• Reproductive barriers: Prevent interbreeding between species (prezygotic and postzygotic barriers)

Evolutionary Patterns

• Convergent evolution: Similar traits evolve independently in unrelated species due to similar selective pressures
  • Example: Wings in birds and bats
• Divergent evolution: Related species evolve different traits due to different selective pressures
  • Example: Adaptive radiation in Galapagos finches
• Coevolution: Two or more species evolve in response to each other
  • Example: Predator-prey relationships, mutualistic interactions

Human Evolution

• Hominin evolution: Evolutionary history of humans and our closest relatives
• Key hominin species:
  • Australopithecus afarensis (Lucy)
  • Homo habilis
  • Homo erectus
  • Neanderthals
• Recent advances in studying human evolution using DNA analysis

Conclusion

• Molecular basis of inheritance provides the foundation for understanding genetics and evolution
• Gene regulation plays a critical role in controlling gene expression
• Mutations and genetic variation contribute to genetic diversity and the potential for evolutionary change
• Population genetics and speciation shape the patterns of evolution
• Human evolution is a fascinating field that continues to reveal our evolutionary history