18. Genes and chromosomes

From greek.doctor

Learning objectives

  • What is the central dogma of molecular biology?
  • Describe the organisation of DNA
  • Describe the composition of the human genome

DNA

The central dogma of molecular biology states that DNA contains instructions for making a protein. These instructions are copied by RNA, which is used to make protein. In short, DNA -> RNA -> protein.

Forming a peptide bond between 2 amino acids requires only 21 kJ/mol and a few enzymes. However, formation of peptide bond between 2 specific amino acids at a particular point in a polypeptide, which occurs during protein synthesis, requires 125 kJ/mol, 200 enzymes and RNA molecules. This shows how much more energetically expensive and complex the conservation of information is.

DNA repair is also extremely energetically inefficient, but it is the price the organism must pay to stay alive.

The structure of DNA

Cytosine (C) and thymine (T) are pyrimidine bases, while adenine (A) and guanine (G) are purine bases. C binds with G with three strong bonds, while A and T are bound with just two. These bonds are hydrogen bonds.

The DNA is organized in a double helix, which contain two intertwined strands of DNA. It is “right handed”, twisting upwards as if driven by a right-handed screw. The two strands are complementary, and they run anti-parallel.

The bases are on the inside of the helix, while the phosphate and deoxyribose units are on the outside. The outside phosphate groups make the DNA negative.

The double helix is binds to proteins called histones, together forming nucleosomes. These nucleosomes have a “beads on a string” appearance under electron microscopy. Many nucleosomes form chromatin, which, during replication, condenses into the X-shaped chromosomes. A chromosome pair consists of two identical chromatids connected at the centre by a centromere.

If a part of DNA contains many alternating T and C residues, one of the strands can coil back on the two other strands, creating a short triple helix.

Genes

Genes are segments of DNA which code for polypeptide chains and RNAs. The DNA of the bacterium E. coli contains 4,6 million base pairs, which code for 4300 proteins and 157 RNAs. Human DNA contains 3,1 billion base pairs, which contain approximately 29 000 genes.

Only 30% of the human genome contains genes, and a very small fraction of this are exons. In fact, only 1,5% of the genome codes for exons, genetic elements which will go on to produce proteins. The remaining 98,5% of the genome does not code for proteins.

45% of the genome is comprised of transposons, genetic elements which can actually jump around in the DNA molecule.

Histones

Histones are proteins the DNA binds to, to support the structure of chromatin. These proteins contain many basic amino acids, making the proteins positively charged, creating a strong binding between them and DNA. There are five types of histone cores: H1, H2A, H2B, H3, and H4.

Reversible covalent modification of histones regulate gene expression, as we’ll see in topic 29.

Summary

  • What is the central dogma of molecular biology?
    • DNA contains instructions for making a protein. These instructions are copied by RNA, which is used to make protein.
  • Describe the organisation of DNA
    • DNA is organized in a right-handed double helix
    • The double helix is bound to histones, forming nucleosomes
    • Many nucleosomes form chromatin
    • Chromatin forms a chromosome, which is comprised of two identical chromatids connected at the centre by a centromere.
  • Describe the composition of the human genome
    • 30% of the genome codes for genes
      • 1,5% of the genome codes for exons
    • 45% of the genome codes for transposons