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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 Virus MS2 Virus l 50 Other viruses Bacteria Genome (kb) 4 5-300 700-5000 Form RNA Linear DNA Circular DNA Circular DNA Yeast Arabidopsis (plant) Fruit fly Mouse Human 13,000 100,000 165,000 3,000,000 3,000,000 Linear DNA arranged as several 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