DNA, genes and chromosomes Revise your BI1505/7 notes Textbook - Purves chapters on “Chromosomes…” and “DNA…”, Lehninger chapter 24 These 3 lectures will cover the organisation of chromosomes and genomes in different organisms Details of DNA replication and gene expression will be covered by other lecturers

The Central Dogma Information flow in cells Language DNA The cat sat on the mat Transcription THE CAT SAT ON THE MAT RNA Translation Protein Le chat s’est assis sur le petit tapis

Why DNA is the genetic material Can be replicated accurately Has capacity to carry information to direct organisation and metabolism in cells Can undergo mutation to enable change and evolution Studies in the 1920s-1940s proved DNA = genes ……..

Genome size increases (roughly) with evolutionary complexity of organism Organism Genome (kb) Form Virus MS2 4 RNA Virus l 50 Linear DNA Other viruses 5-300 Circular DNA Bacteria 700-5000 Circular DNA Yeast 13,000 Linear DNA Arabidopsis (plant) 100,000 arranged Fruit fly 165,000 as Mouse 3,000,000 several Human 3,000,000 chromosomes

Human Chromosomes

Chromatin and histones In eukaryotes, the first level of DNA packing is the chromatin fibre Chromatin is formed by wrapping the DNA around complexes of the 4 histone proteins (2 molecules each of histones H2A, H2B, H3, H4) to form “beads on string” arrangement - the beads are nucleosomes See figures 24-23, 24-24, table 24-3 in Lehninger Chromatin is of 2 different types - euchromatin (where most of the active genes are) and heterochromatin (no active genes). Some regions of genome can switch between these 2 states (facultative heterochromatin)

Nucleosomes

Chromosome structure - packing ratio Packing ratio is the length of the DNA divided by the length into which it’s packaged Smallest human chromosome (21) has 4x107 bp of DNA, 10 times size of E. coli genome Equivalent to 14mm of extended DNA In most condensed state the chromosome is about 2mm long Packing ratio = 14000/2 = 7000 So, there must be an efficient packaging mechanism

Higher level DNA packing To achieve packing ratio of 7000, chromatin is organised into several levels of complex folded and coiled structures See relevant figures in Purves or in Lehninger

Chromatin packaging

Position-effect variegation (PEV) State of chromatin (euchromatin, heterochromatin) can affect gene expression A gene could be moved to a heterochromatic region by an inversion Heterochromatin’s structure tends to switch off gene expression

An example of PEV A mutant allele of the w gene in Drosophila causes eyes to be white (wild-type is red) An inversion of part of the X chromosome causes eyes to have red and white patches This is because of PEV switching off w gene in some cell lines in the eye The boundary between heterochromatin and euchromatin is not exactly the same in all cell lines, hence eyes are mosaic