Molecular Basis of Inheritance - Eukaryotic Chromosomes
- Eukaryotic chromosomes
- Found in the nucleus of eukaryotic cells
- Composed of DNA and proteins
- Carry genetic information
- Structure of eukaryotic chromosomes
- Consists of chromatin fibers
- Chromatin fibers are made up of DNA and proteins
- Can be condensed or decondensed
- Different levels of organization
- Levels of organization
- DNA double helix
- Nucleosomes
- Chromatin fibers
- Loops
- Coils
- Supercoils
- DNA double helix
- Double-stranded structure
- Composed of nucleotides
- Base pairing: A-T, G-C
- Antiparallel strands
- Backbone made up of sugar and phosphate molecules
- Nucleosomes
- Basic unit of DNA packaging
- Consists of a core particle and linker DNA
- Core particle composed of histone proteins
- DNA wraps around the core particle
- Chromatin fibers
- Nucleosomes packed together
- Further coiled and condensed
- Forms chromatin thread
- Loops
- Chromatin fibers form loops
- Looping promotes gene regulation
- Interaction of different regulatory regions
- Coils
- Further coiling of looped chromatin fibers
- Compact structure of chromosomes
- Essential for proper chromosome segregation
- Supercoils
- Additional twisting of coiled chromatin fibers
- Helps maintain chromosome stability
- Ensures proper DNA packaging
- Chromosome territories
- Each chromosome occupies a specific region in the nucleus
- Topological organization of chromosomes
- Chromosome territories help regulate gene expression
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- Chromosome abnormalities
- Structural abnormalities
- Deletion: Loss of a portion of a chromosome
- Duplication: Presence of extra copies of a chromosome segment
- Inversion: Reversal of a chromosome segment orientation
- Translocation: Exchange of chromosome segments between non-homologous chromosomes
- Numerical abnormalities
- Aneuploidy: Extra or missing chromosomes
- Trisomy: Presence of an extra chromosome (e.g., Down syndrome)
- Monosomy: Absence of a chromosome (e.g., Turner syndrome)
- Polyploidy: Extra sets of chromosomes (e.g., tetraploidy, triploidy)
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- Chromosome disorders
- Down syndrome (Trisomy 21)
- Extra copy of chromosome 21
- Intellectual disability, characteristic facial features, and developmental delays
- Occurs in approximately 1 in 800 births
- Risk increases with maternal age
- Turner syndrome (Monosomy X)
- Missing or partially missing X chromosome in females
- Short stature, infertility, and webbed neck
- Occurs in approximately 1 in 2,500 female births
- Klinefelter syndrome (XXY)
- Extra X chromosome in males
- Infertility, reduced testosterone levels, and developmental delays
- Occurs in approximately 1 in 500 male births
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- Regulation of gene expression
- Gene expression can be regulated at multiple steps:
- Transcriptional regulation: Control of mRNA synthesis
- Post-transcriptional regulation: Processing, transport, and stability of mRNA
- Translational regulation: Control of protein synthesis from mRNA
- Post-translational regulation: Modifications and degradation of proteins
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- Transcriptional regulation
- Regulatory regions: Promoters and enhancers
- Transcription factors:
- Proteins that bind to specific DNA sequences
- Activators enhance gene expression
- Repressors inhibit gene expression
- Chromatin remodeling:
- Covalent modifications of histones and DNA
- Affects accessibility of DNA to transcription factors
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- Post-transcriptional regulation
- RNA processing:
- Splicing: Removal of introns and joining of exons
- Alternative splicing: Variable exon usage
- RNA editing: Changes in nucleotide sequence
- RNA transport: Movement of mRNA from nucleus to cytoplasm
- mRNA stability: Degradation or stabilization of mRNA molecules
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- Translational regulation
- Initiation factors: Proteins required for translation initiation
- Can be regulated by various factors (e.g., signaling pathways, RNA-binding proteins)
- microRNAs (miRNAs):
- Small RNA molecules that bind to mRNA
- Inhibit translation or promote mRNA degradation
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- Post-translational regulation
- Protein modifications:
- Phosphorylation: Addition of a phosphate group
- Acetylation: Addition of acetyl groups
- Methylation: Addition of methyl groups
- Ubiquitination: Tagging for degradation
- Protein degradation:
- Proteasomes: Complexes that degrade proteins
- Ubiquitin-proteasome system
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- Epigenetics
- Heritable changes in gene expression without alterations in DNA sequence
- Influenced by environmental factors and development
- Mechanisms:
- DNA methylation: Addition of a methyl group to DNA
- Histone modifications: Covalent modifications of histone proteins
- Non-coding RNAs: Influence gene expression at multiple levels
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- Genetic and environmental factors
- Interplay between genes and environment
- Genetic predisposition: Increased susceptibility to certain conditions
- Environmental factors can modify gene expression and influence phenotype
- Examples:
- Gene-environment interactions in cancer development
- Nutritional influences on gene expression and health outcomes
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- Evolutionary significance of genetic variation
- Genetic variation is the raw material for evolution
- Populations with greater genetic variation have higher adaptive potential
- Sources of genetic variation:
- Mutations: Changes in DNA sequence
- Sexual reproduction: Genetic recombination
- Natural selection acts on genetic variation to drive evolution
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- Hardy-Weinberg Principle
- Describes genetic equilibrium in idealized populations
- The equation: p^2 + 2pq + q^2 = 1
- p and q represent the frequencies of alleles in a population
- p^2 represents the frequency of the homozygous dominant genotype
- q^2 represents the frequency of the homozygous recessive genotype
- 2pq represents the frequency of the heterozygous genotype
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- Genetic drift
- Random changes in allele frequencies in a population
- More pronounced in small populations
- Founder effect: When a small group of individuals establish a new population
- Example: The Amish population in the United States
- Bottleneck effect: Sharp reduction in population size
- Example: The cheetah population
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- Gene flow
- Movement of alleles between populations
- Increases genetic variation within a population
- Can counteract genetic drift and maintain genetic diversity
- Example: Migration of individuals between different regions
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- Natural selection
- Process by which individuals with certain traits have higher reproductive success
- Acts on genetic variation already present in a population
- Types of natural selection:
- Stabilizing selection: Selects against extreme phenotypes
- Directional selection: Shifts the average phenotype toward one extreme
- Disruptive selection: Selects for extreme phenotypes and against intermediate phenotypes
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- Sexual selection
- Differential reproductive success based on traits related to mating
- Intra-sexual selection: Competition between members of the same sex for access to mates
- Example: Male-male competition in deer species
- Inter-sexual selection: Mate choice based on traits preferred by the opposite sex
- Example: Peacock’s tail in peafowls
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- Speciation
- Process by which new species arise
- Two major modes of speciation:
- Allopatric speciation: Geographic barriers separate populations
- Sympatric speciation: New species form within the same geographic area
- Example: Darwin’s finches in the Galapagos Islands
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- Molecular clock
- Uses the rate of genetic mutations to estimate the time of divergence between species
- Assumes a constant rate of mutation accumulation over time
- Can provide insights into evolutionary relationships and the timing of evolutionary events
- Example: Estimating the divergence between humans and other primates
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- Phylogenetics
- Study of evolutionary relationships among species
- Uses phylogenetic trees or cladograms to represent relationships
- Based on shared characteristics or genetic information
- Example: Constructing a phylogenetic tree for different bird species
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- Human evolution
- Evolutionary history of the Homo genus
- Key milestones and species:
- Ardipithecus: Early hominins, adapted to both arboreal and bipedal locomotion
- Australopithecus: Bipedal hominins, predecessors to the Homo genus
- Homo habilis: The “handy man,” earliest known tool-user
- Homo erectus: First hominins to have a wide geographic distribution
- Homo neanderthalensis: Close relatives to modern humans, went extinct
- Homo sapiens: Modern humans
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- Applications of genetics and evolution
- Forensic genetics: DNA profiling for identification
- Medical genetics: Diagnosis and treatment of genetic disorders
- Agricultural genetics: Improving crop yields and livestock breeding
- Conservation genetics: Protecting endangered species and preserving genetic diversity
- Evolutionary medicine: Studying how evolution influences human health