Genetics and Evolution

Molecular Basis of Inheritance

Formation of Chromatin Fibre

  • Introduction to Chromatin Fibre
  • Structure and Components of Chromatin Fibre
  • Nucleosomes and Histones
  • Histone Modifications
  • Heterochromatin and Euchromatin ''

Introduction to Chromatin Fibre

  • Chromatin fibre is a complex of DNA, proteins, and RNA found in the nucleus of eukaryotic cells.
  • It plays a critical role in packaging DNA to fit inside the nucleus.
  • Chromatin fibre undergoes structural changes during various cellular processes.
  • The organization of chromatin fibre is tightly regulated to control gene expression. ''

Structure and Components of Chromatin Fibre

  • Chromatin fibre is made up of repeating subunits called nucleosomes.
  • Nucleosomes consist of DNA wrapped around a protein core called histones.
  • Histones are positively charged proteins that help in DNA packaging.
  • Linker DNA connects adjacent nucleosomes.
  • Other proteins, such as histone variants and non-histone proteins, also contribute to chromatin fibre structure. ''

Nucleosomes and Histones

  • Nucleosomes are composed of eight histone proteins: two copies each of H2A, H2B, H3, and H4.
  • The histone proteins form an octamer core around which DNA is wrapped.
  • The DNA wraps around the histone octamer in 1.65 turns, forming a left-handed superhelix.
  • This wrapping of DNA results in condensed chromatin structure and helps in DNA compaction. ''

Histone Modifications

  • Histone proteins undergo various chemical modifications, including acetylation, methylation, phosphorylation, etc.
  • These modifications can affect chromatin structure and gene expression.
  • For example, acetylation of histones is associated with gene activation, while methylation can be associated with gene repression.
  • Histone modifications can be added or removed by specific enzymes, called histone modifying enzymes. ''

Heterochromatin and Euchromatin

  • Chromatin fibre can exist in two main forms: heterochromatin and euchromatin.
  • Heterochromatin is a highly condensed form of chromatin, usually transcriptionally inactive.
  • Euchromatin is a less condensed form of chromatin, usually transcriptionally active.
  • The balance between heterochromatin and euchromatin is crucial for proper gene regulation and cellular function. ''

Conclusion

  • Chromatin fibre is a dynamic structure that undergoes changes to control gene expression.
  • Nucleosomes and histones play a crucial role in the packaging and organization of DNA.
  • Histone modifications can affect chromatin accessibility and gene expression.
  • The balance between heterochromatin and euchromatin is essential for proper gene regulation. (Note: Please continue creating slides 11 to 20)

X-Inactivation and Barr Body Formation

  • X-inactivation is a process that occurs in female mammals to compensate for the presence of two X chromosomes.
  • One of the X chromosomes in each cell is randomly inactivated and forms a heterochromatic structure called a Barr body.
  • The Barr body ensures that both males and females have the same dosage of X-linked genes.
  • The inactivation of an X chromosome is permanent and is passed on to all daughter cells. ''

Chromatin Remodeling

  • Chromatin remodeling refers to the changes in chromatin structure that allow regulatory factors to access DNA.
  • Remodeling complexes use ATP to alter nucleosome positions or to evict nucleosomes, making DNA more accessible.
  • Chromatin remodeling is essential for gene activation, DNA repair, and other cellular processes.
  • Examples of chromatin remodeling complexes include SWI/SNF and ISWI complexes. ''

Epigenetics and Chromatin Modifications

  • Epigenetics refers to heritable changes in gene expression that do not involve changes to the DNA sequence.
  • Chromatin modifications, such as histone modifications and DNA methylation, play a crucial role in epigenetic regulation.
  • These modifications can be maintained through cell divisions and can affect gene expression patterns.
  • Epigenetic changes can be influenced by environmental factors and can be reversible. ''

Chromatin Immunoprecipitation (ChIP)

  • ChIP is a technique used to study protein-DNA interactions and chromatin modifications.
  • In ChIP, specific proteins or chromatin modifications are “pulled down” using antibodies.
  • The DNA that is associated with the protein or modification of interest can then be analyzed.
  • ChIP allows us to determine which regions of the genome are bound by specific proteins and study their functional role. ''

Chromosome Conformation Capture (3C)

  • 3C is a molecular biology technique used to study the three-dimensional organization of the genome.
  • In 3C, cross-linking is performed to freeze interactions between DNA segments that are spatially close in the nucleus.
  • The cross-linked DNA is then digested, ligated, and analyzed using PCR or sequencing.
  • 3C allows us to determine the physical proximity of specific genomic regions and study their interactions. ''

Long Non-Coding RNAs (lncRNAs)

  • lncRNAs are a class of non-coding RNAs that are longer than 200 nucleotides.
  • They play diverse regulatory roles in gene expression, chromatin organization, and cellular processes.
  • lncRNAs can interact with chromatin, DNA, and proteins to modulate gene expression and chromatin structure.
  • Examples of lncRNAs include Xist, HOTAIR, and MALAT1. ''

Small Interfering RNAs (siRNAs)

  • siRNAs are small RNA molecules that regulate gene expression through RNA interference (RNAi).
  • They can bind to target messenger RNAs (mRNAs), leading to their degradation or translational inhibition.
  • siRNAs are involved in many biological processes, including defense against viral infections and regulation of gene expression.
  • Researchers have used siRNAs as tools for gene silencing and studying gene function. ''

RNA Interference (RNAi)

  • RNAi is a biological process in which RNA molecules silence gene expression.
  • It can be triggered by endogenous small RNAs or introduced siRNAs.
  • RNAi regulates gene expression at the post-transcriptional level, impacting mRNA stability or translation.
  • RNAi has applications in gene therapy, crop improvement, and functional genomics research. ''

Chromatin Disorders and Diseases

  • Abnormalities in chromatin structure and function can lead to various genetic disorders and diseases.
  • Examples include Rett syndrome, Kabuki syndrome, and immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome.
  • Dysregulation of chromatin remodeling, histone modifications, and DNA methylation are often observed in cancer.
  • Understanding chromatin dynamics and its role in disease can lead to new therapeutic strategies. ''

Summary

  • Chromatin fibre is a complex structure formed by DNA and associated proteins.
  • Nucleosomes and histones play a critical role in DNA packaging and compaction.
  • Chromatin undergoes various modifications and remodeling to regulate gene expression.
  • Epigenetic modifications can influence gene expression patterns.
  • Techniques like ChIP and 3C help in studying chromatin and genomic interactions.
  • Long non-coding RNAs and small interfering RNAs are involved in gene regulation.
  • Chromatin disorders and abnormalities contribute to human diseases.
  • Understanding chromatin dynamics is crucial for unraveling the molecular basis of inheritance. (Note: Please continue creating slides 21 to 30)

DNA Replication

  • DNA replication is the process by which DNA is synthesized. It occurs before cell division.
  • The original DNA molecule serves as a template for the synthesis of a new complementary strand.
  • The replication process is highly accurate due to the base-pairing rules (A-T, G-C) and proofreading mechanisms.
  • DNA replication is carried out by a group of enzymes known as DNA polymerases.
  • Each DNA strand is replicated in a semi-conservative manner, resulting in two identical daughter DNA molecules. ''

Transcription

  • Transcription is the process by which an RNA molecule is synthesized using a DNA template.
  • It is the first step in gene expression and occurs in the nucleus of eukaryotic cells.
  • RNA polymerase enzyme catalyzes the formation of a complementary RNA strand using DNA as a template.
  • The newly synthesized RNA molecule undergoes post-transcriptional modifications, such as capping, splicing, and polyadenylation.
  • Transcription plays a crucial role in regulating gene expression and producing different types of RNA molecules. ''

Translation

  • Translation is the process by which proteins are synthesized using the information encoded in RNA molecules.
  • It occurs on ribosomes in the cytoplasm.
  • During translation, the sequence of nucleotides in mRNA is decoded into a sequence of amino acids.
  • Transfer RNA (tRNA) molecules bring the appropriate amino acids to the ribosome.
  • The process of translation involves initiation, elongation, and termination. ''

Genetic Code

  • The genetic code is a set of rules that determines how nucleotide sequences are translated into amino acid sequences.
  • It is a triplet code, meaning that three nucleotides (codon) encode one amino acid.
  • There are a total of 64 possible codons, including start and stop codons.
  • The genetic code is almost universal across organisms, with a few exceptions.
  • Examples: AUG codes for methionine, UUU codes for phenylalanine, UGA is a stop codon. ''

Gene Regulation

  • Gene regulation refers to the mechanisms that control the expression of genes.
  • It allows cells to respond to various signals and environmental changes.
  • Gene regulation can occur at multiple levels, including transcriptional, post-transcriptional, translational, and post-translational.
  • Transcriptional regulation is the most common and important mechanism.
  • It involves the binding of regulatory proteins (transcription factors) to specific DNA sequences. ''

Operons

  • Operons are functional units in prokaryotes that consist of a cluster of genes and their regulatory elements.
  • They allow for the coordinate regulation of gene expression.
  • The operon consists of a promoter, operator, and genes coding for proteins involved in the same metabolic pathway.
  • The lac operon is a well-known example of an inducible operon.
  • The trp operon is an example of a repressible operon. ''

Transcription Factors

  • Transcription factors are proteins that bind to specific DNA sequences and regulate gene expression.
  • They can activate or repress the transcription of target genes.
  • Transcription factors can interact with other proteins and modify chromatin structure to control gene expression.
  • Different combinations of transcription factors determine cell-specific gene expression patterns.
  • Mutations in transcription factor-encoding genes can lead to developmental disorders and diseases. ''

Mutation

  • Mutations are changes in the DNA sequence that can affect gene expression and protein structure.
  • Mutations can occur spontaneously or as a result of environmental factors, replication errors, or exposure to mutagens.
  • Types of mutations include point mutations, insertions, deletions, and chromosomal rearrangements.
  • Some mutations can be beneficial, neutral, or deleterious, depending on their effects.
  • Mutations are a driving force in evolution and can lead to the development of new traits and species. ''

Genetic Disorders

  • Genetic disorders are diseases that result from abnormalities in DNA sequence or chromosomal structure.
  • They can be inherited or occur de novo (new mutations).
  • Examples of genetic disorders include cystic fibrosis, Down syndrome, sickle cell anemia, and Duchenne muscular dystrophy.
  • Genetic disorders can be diagnosed through various techniques, including karyotyping, DNA sequencing, and genetic testing.
  • Some genetic disorders can be treated or managed through early diagnosis and medical interventions. ''

Gene Therapy

  • Gene therapy is a promising approach for treating genetic disorders by introducing functional genes into cells.
  • It involves delivering therapeutic genes using viral vectors, liposomes, or other delivery systems.
  • Gene therapy can be used to replace defective genes, introduce new genes, or modify gene expression.
  • Challenges in gene therapy include the efficiency of gene delivery, immune responses, and long-term safety concerns.
  • Despite the challenges, gene therapy offers great potential for the treatment of genetic disorders.