Genome Anatomy

DNA structure

• 2’ deoxyribose sugar (no OH on C2)

• 1’ base

• 3’, 5’ phosphate group

what direction is DNA written

• 5’ → 3’

• direction in which DNA and RNA are synthesised

DNA replication

1. DNA gyrase unwinds the helix

2. Hydrogen bonds between bases are broken by DNA helicase

3. Free nucleotides are present in the nucleus→ can link to complementary bases.

4. DNA polymerase joins adjacent nucleotides to reform sugar-phosphate backbone, linking the new strands together.

DNA replication in leading vs lagging strand

• leading strand allows continuous extension

• lagging strand causes discontinuous replication:

  • creates okazaki fragments

  • joined by DNA ligase

telomeres

• found at the end of chromosome

• TTAGGG telomeric repeat sequence

• telomeres shorten with somatic cell division→ finite number of divisions

nucleosome

• basic structural unit of DNA packaging in eukaryotic cells

• segment of DNA wound around histone proteins

chromosome landmarks

diploidy

• n=23

• 2n=46

• 2 copies of every gene→ paternal, maternal

dosage of genes

• haploinsufficiency→ one is not enough

• exception is the X chromosome

human genome

• 3000 Mbp dsDNA per haploid genome

• >90% is non-coding

• approx. 20 000 protein coding genes

mitochondrial genome

• circular not linear

• 37 genes

• cytoplasmic not nuclear

• maternal inheritance

sequence classes

1. single-copy sequences (non-repetitive)

   1. genes

2. repetitive sequences

   1. satellite DNA→ large blocks of repetitive sequence

   2. interspersed repeats

genes

• functional units of DNA

  • genes are expressed

components of genes

• exons

• introns

• regulatory sequences→ promoters, enhancers, locus control regions

satellite DNA

• large blocks at centromeres and heterochromatic chromosomal regions

• tandemly repeated sequences

alphoid DNA

• type of satellite DNA found at centromeres

• 171-bp repeat unit

• shows chromosome specific sequence variation

• alphoid DNA is required for assembly of centromere

interspersed repeats

• scattered around the genome

• individual copies are present at many locations

• e.g. Alu repeat

gene structure

gene families

• evolution of genes progresses by duplication and divergence

• most genes belong to a family of structurally related genes

• members of gene family may be clustered or widely dispersed

processed genes

• intronless copies of other genes

  • usually remote from parent gene

• reverse transcription and reintegration

  • retroviruses

• occasionally remain functional

• most are non-functional