Nature of the Gene and Genome

• Nucleus


  The information store of the cell, storing genetic information, and is enclosed within two concentric membranes that form the nuclear envelope
• What does the nucleus contain and what are its functions?

  • Contains molecules of DNA, which are extremely long polymers that encode the genetic information of the organism
  • Each individual strand/molecule of DNA is called a chromosome
  • Site of DNA packaging
  • Contains nucleolus and produces ribosomes
  • Site of DNA replication and transcription
  • Communicates with cytosol via nuclear pores

  
• What is the genome

  Each cell nucleus contains an identical complement of chromosomes in two copies, each copy is a genome
• Each chromosome is one long DNA molecule and genes are functional regions of this DNA

  
• DNA is a double helix
• Chromosomes in the human genome

  • 23 pairs, 22 autosomes (non-sex chromosomes), 1 sex chromosome

  
• The human genome also includes the circular chromosome found inside the cellular organelles called mitochondria — they have their own separate genomes

  
• Chromosomes in the nucleus are linear in shape whereas those found in mitochondria are circular

  
• Chromosomes


  • Usually found in pairs, with one being inherited from the mother (maternal homolog) and the other from the father (paternal homolog)
  • Structures at the ends are telomeres and those at the centre are centromeres
  • The most important function is to carry genes
• Different organisms have different numbers of chromosomes, the number doesn't equal the complexity of an organism
• Chromatin


  A double-stranded helical structure of DNA and chromosomal DNA is packaged inside microscopic nuclei with the aid of histones, which are positively charged proteins that strongly adhere/attach to negatively charged DNA and form complexes called nucleosomes

  
• Nucleosomes


  • Each nucleosome is composed of DNA wound 1.65 times around 8 histone proteins
  • Nucleosomes then fold up to form 30nm chromatin fibres, which forms loops averaging 300nm in length
  • The 300nm coiled fibres are compressed and folded to produce up two 15nm wide fibre, which is tightly coiled into the chromatid of the chromosome

  
• What is a nucleosome?

  The basic repeating structural and functional unit of chromatin, containing 8 histone proteins and about 146 base pairs of DNA

  
• Nucleosome


  • Two H2A, H2B, H3 and H4 histones come together to form a histone octamer that binds and wraps approx. 1.7 tons of DNA/about 146 base pairs
  • The addition of one H1 protein wraps another 20 base pairs, resulting in two full forms around the octamer and forming a structure called a chromatosome

  
• The 166 BP isn't very long, considering each chromosome contains over 100 million BP of DNA on average. Therefore, every chromosome contains hundreds of thousands of nucleosomes and these nucleosomes are joined by the DNA that run between them, referred to as linker DNA

  
• Each chromosome is a long chain of nucleosomes, which gives the appearance of a string of beads

  
• What is a gene

  A DNA segment containing instructions for making a particular product, including the regulatory elements

  
• Regulatory elements

  • Promotor is a very important regulatory element, as you can't make a particular product from a gene without it
  • Additional regulatory elements include introns, exons and untranslated regions
  • Genes differ in size and number of exons/introns

  
• Central Dog

  Genetic information flows from DNA to RNA to protein

  
• Central Dogma


  1. Transcription - synthesis of mRNA transcript from DNA

  2. Translation - protein production from mRNA transcript
• DNA can't be directly converted to protein; it must be converted to RNA first via transcription, which is then converted to protein via translation
• DNA replication isn't a part of the central dogma. DNA can be made from other DNA molecules

  
• DNA


  Deoxyribonucleic acid, a type of nucleic acid found in cells
• RNA


  Ribonucleic acid, a type of nucleic acid found in cells

  
• DNA vs RNA

  • DNA exists as a double-stranded structure, RNA exists as a single-stranded structure
  • RNA can base pair with DNA but not capable of forming the B-form of the double helix (forms A structure)
  • Because RNA is single stranded, it forms complicated 3D structures

  
• Major types of RNA

  • Messenger RNA (mRNA)
  • Transfer RNA (tRNA)
  • Ribosomal RNA (rRNA)
• Coding and non-coding RNA

  Not all RNA code for proteins; 4% of total RNA is made of coding RNA, the remaining are non-coding RNA
• Non-coding RNA


  • Ribosomal RNA (rRNA) and transfer RNA(tRNA) are used in the various protein translational apparatus
  • Small nuclear RNA (snRNA) is found in eukaryotes and is part of the splicing apparatus
  • Small nucleolar RNA (snoRNA) is involved in methylation of rRNA
  • Small cytoplasmic RNA (scRNA) plays a role in the expression of specific genes

  
• Structure of RNA


  • Unlike DNA, tertiary structure depends on length and sequence of RNA
  • tRNA secondary structure shows characteristic stems (base paired — like A form region) and loops
  • Tertiary structures adopt complex configurations