Genetics and Evolution: Molecular Basis of Inheritance - Formation of Heterochromatin (700nm)

  • In eukaryotic cells, DNA is organized into chromatin, which consists of DNA and proteins.
  • Chromatin can exist in two forms: euchromatin and heterochromatin.
  • Heterochromatin is densely packed and appears dark under a light microscope.
  • Formation of heterochromatin involves the condensation of chromatin structure.
  • Heterochromatin plays a role in gene silencing and maintaining genomic stability.

Slide 11: Structure and Function of Centromeres

  • Centromeres are specialized regions of DNA that play a crucial role in cell division.
  • They are responsible for the attachment of spindle fibers during mitosis and meiosis.
  • Centromeres contain highly repetitive DNA sequences that are rich in the protein called CENP-A.
  • CENP-A helps in the formation of kinetochores, which are essential for proper chromosome segregation.
  • Centromeres play a role in maintaining the stability and integrity of chromosomes.

Slide 12: Telomeres and Aging

  • Telomeres are the protective caps located at the ends of chromosome.
  • They consist of repetitive DNA sequences and associated proteins.
  • Telomeres prevent the degradation and fusion of chromosomes.
  • Telomeres gradually shorten with each round of cell division due to the replication process.
  • Telomere shortening has been linked to cellular aging and the development of age-related diseases.

Slide 13: Epigenetics and Gene Regulation

  • Epigenetics refers to the study of heritable changes in gene expression that do not involve changes in the underlying DNA sequence.
  • Epigenetic modifications can be influenced by environmental factors, lifestyle choices, and aging.
  • These modifications can alter the structure of DNA and its associated proteins, leading to changes in gene expression.
  • Examples of epigenetic modifications include DNA methylation and histone modifications.
  • Epigenetic changes can have a significant impact on phenotype and disease development.

Slide 14: DNA Methylation and Gene Silencing

  • DNA methylation is an epigenetic modification that involves the addition of a methyl group to the DNA molecule.
  • Methylation typically occurs at cytosine residues in CpG dinucleotides.
  • DNA methylation can lead to gene silencing by blocking the binding of transcription factors and other regulatory proteins.
  • Gene silencing through DNA methylation is essential for normal cellular processes such as X-chromosome inactivation and genomic imprinting.
  • Aberrant DNA methylation patterns have been associated with various diseases, including cancer.

Slide 15: Histone Modifications and Chromatin Remodeling

  • Histone proteins play a crucial role in the packaging of DNA into chromatin.
  • Histone modifications, such as acetylation, methylation, phosphorylation, and ubiquitination, can affect chromatin structure and gene expression.
  • Acetylation of histones is generally associated with gene activation, while methylation can be either activating or repressive, depending on the specific lysine or arginine residue modified.
  • Histone modifications can also attract chromatin remodeling complexes, which alter the positioning of nucleosomes along the DNA.
  • These modifications and remodeling events contribute to the dynamic nature of chromatin and gene regulation.

Slide 16: Chromosomal Aberrations and Genetic Disorders

  • Chromosomal aberrations are structural abnormalities in chromosomes that can result in genetic disorders.
  • Examples of chromosomal aberrations include deletions, duplications, inversions, translocations, and aneuploidies.
  • These aberrations can occur spontaneously or be inherited from parents with chromosomal abnormalities.
  • Chromosomal aberrations can disrupt the function of genes and lead to developmental delays, intellectual disabilities, and other health conditions.
  • Techniques such as karyotyping and fluorescence in situ hybridization (FISH) are used to detect and analyze chromosomal aberrations.

Slide 17: Importance of Genome Sequencing

  • Genome sequencing refers to the process of determining the complete DNA sequence of an organism’s genome.
  • Genome sequencing provides valuable information about an organism’s genetic makeup and can help in understanding its biology and evolution.
  • It has enabled the identification of genes associated with diseases and the development of personalized medicine.
  • Genome sequencing also plays a vital role in agriculture, conservation biology, and biotechnology applications.
  • Advances in sequencing technologies have led to faster and more cost-effective sequencing, making it increasingly accessible for research and medical purposes.

Slide 18: Next-Generation Sequencing Techniques

  • Next-generation sequencing (NGS) refers to the modern sequencing technologies that can generate massive amounts of DNA sequence data.
  • NGS methods include Illumina sequencing, Ion Torrent sequencing, and Pacific Biosciences sequencing.
  • These techniques utilize different mechanisms to read and sequence DNA molecules.
  • NGS has revolutionized genomics research by enabling comprehensive analysis of genomes, transcriptomes, and epigenomes.
  • NGS has diverse applications, including genome assembly, variant calling, transcriptome profiling, and metagenomics.

Slide 19: CRISPR-Cas9: Revolutionary Genome Editing Tool

  • CRISPR-Cas9 is a powerful genome editing tool that utilizes a bacterial defense system to target and modify specific DNA sequences.
  • Cas9 is an endonuclease enzyme that can be guided to specific DNA sites by a guide RNA molecule.
  • Once at the target site, Cas9 induces a double-stranded break in the DNA.
  • This break can be repaired by the cell’s DNA repair machinery through non-homologous end joining (NHEJ) or homology-directed repair (HDR).
  • CRISPR-Cas9 has revolutionized genetic research, as it allows precise genome editing in various organisms, including humans.

Slide 20: Applications of CRISPR-Cas9

  • CRISPR-Cas9 has numerous applications in biomedical research and biotechnology.
  • In research, it enables the study of gene function through gene knockout or knock-in experiments.
  • CRISPR-Cas9 can be used to develop disease models, screen drug targets, and explore genetic interactions.
  • In biotechnology, CRISPR-Cas9 holds promise for genome engineering of crops and livestock for improved traits and disease resistance.
  • CRISPR-Cas9 is also being investigated for potential therapeutic applications, such as gene therapy and gene editing to treat genetic disorders.

Slide 21: Structure and Function of Ribosomes

  • Ribosomes are cellular organelles responsible for protein synthesis.
  • They exist as two subunits: a large subunit and a small subunit.
  • The large subunit contains three binding sites: A site, P site, and E site.
  • The A site binds incoming aminoacyl-tRNA, the P site holds the tRNA carrying the growing polypeptide chain, and the E site is the exit site.
  • Ribosomes play a crucial role in translating mRNA into a functional protein.

Slide 22: Transcription: DNA to RNA

  • Transcription is the process of synthesizing RNA molecules from a DNA template.
  • It involves three stages: initiation, elongation, and termination.
  • During initiation, RNA polymerase binds to the promoter region of the DNA.
  • In elongation, RNA polymerase unwinds the DNA and synthesizes the RNA molecule using complementary base pairing.
  • Termination occurs when RNA polymerase reaches a transcription termination signal.

Slide 23: RNA Processing: Modifications before Translation

  • RNA processing refers to the modifications that occur to the primary transcript before it can be translated into a protein.
  • These modifications include 5’ cap addition, polyadenylation, and splicing.
  • The 5’ cap protects the mRNA from degradation and helps in the recognition of the mRNA by the ribosome.
  • Polyadenylation involves the addition of a poly-A tail to the 3’ end of the mRNA, which also aids in mRNA stability and translation efficiency.
  • Splicing removes introns and joins together the exons to produce a mature mRNA molecule.

Slide 24: Translation: RNA to Protein

  • Translation is the process by which the mRNA sequence is decoded to synthesize a protein.
  • It occurs at the ribosomes in the cytoplasm.
  • Translation involves three major steps: initiation, elongation, and termination.
  • During initiation, the small ribosomal subunit binds to the mRNA and identifies the start codon.
  • In elongation, amino acids are added to the growing polypeptide chain based on codon-anticodon recognition.
  • Termination occurs when a stop codon is reached, and the protein is released from the ribosome.

Slide 25: Genetic Code: The Language of DNA and RNA

  • The genetic code is a set of rules that relates the sequence of nucleotides in DNA or RNA to a specific amino acid sequence in a protein.
  • The genetic code is universal, meaning that it is the same in almost all organisms.
  • It is degenerate, meaning that multiple codons can specify the same amino acid.
  • Start codon (AUG) initiates translation, and stop codons (UAA, UAG, UGA) signal the end of translation.
  • Examples of codons and the corresponding amino acids are: UUU (Phenylalanine), CAA (Glutamine), AUG (Methionine), and UAA (Stop).

Slide 26: Mutations: Changes in Genetic Information

  • Mutations are changes in the DNA sequence that produce heritable variations.
  • They can occur due to errors during DNA replication, chemical or physical damage to DNA, or exposure to mutagens.
  • Types of mutations include point mutations, insertions, deletions, and chromosomal rearrangements.
  • Point mutations can be silent, missense, or nonsense mutations, depending on whether they result in no, altered, or premature termination of protein synthesis.
  • Mutations can lead to genetic disorders, contribute to evolutionary processes, or have no significant effect on an organism.

Slide 27: DNA Repair Mechanisms

  • DNA repair mechanisms are cellular processes that correct errors and damages in the DNA sequence.
  • These mechanisms play a crucial role in maintaining genomic stability and preventing the accumulation of mutations.
  • Types of DNA repair mechanisms include base excision repair, nucleotide excision repair, mismatch repair, and homologous recombination.
  • DNA repair mechanisms can recognize and remove damaged or mismatched nucleotides and replace them with the correct ones.
  • Failure of DNA repair mechanisms can lead to the development of genetic diseases and cancer.

Slide 28: Recombinant DNA Technology: Genetic Engineering

  • Recombinant DNA technology involves the manipulation and transfer of genetic material between different organisms.
  • It enables the creation of genetically modified organisms (GMOs) that possess desirable traits.
  • Techniques used in genetic engineering include isolation of DNA, restriction enzymes, DNA ligation, and gene transfer methods.
  • Recombinant DNA technology has applications in agriculture, medicine, and industrial processes.
  • Examples of applications include the production of genetically engineered crops, therapeutic proteins, and gene therapies.

Slide 29: Polymerase Chain Reaction (PCR)

  • Polymerase Chain Reaction (PCR) is a technique used to amplify specific DNA sequences.
  • It is a three-step process: denaturation, annealing, and extension.
  • Denaturation involves heating the DNA to separate the two strands.
  • Annealing involves cooling the DNA to allow primers to bind to the target sequences.
  • Extension involves DNA synthesis by a heat-stable DNA polymerase enzyme, resulting in the amplification of the target DNA.
  • PCR has numerous applications, including DNA cloning, genetic testing, and forensic analysis.

Slide 30: Gene Expression and Regulation

  • Gene expression refers to the process by which genetic information is used to synthesize functional gene products such as proteins.
  • Regulation of gene expression allows cells to respond to environmental cues and maintain homeostasis.
  • Gene expression is regulated at multiple levels, including transcriptional, post-transcriptional, translational, and post-translational regulation.
  • Transcriptional regulation involves the control of gene expression by transcription factors and regulatory elements.
  • Post-transcriptional regulation includes mRNA processing, transport, and degradation.