Organization of the human genome

• Genome structure

• Nuclear vs. mitochondrial genomes

• Gene families

• Transposable elements

• Other repeated sequences

Organization of the human genome

• Mitochondrial genome–Small (16.5 kb) circular DNA–rRNA, tRNA and protein encoding genes (37)–1 gene/0.45 kb–Very few repeats–No introns–93% coding–No recombination–Maternal inheritance

Organization of the human genome

Limited autonomy of mt genomesmt encoded nuclear

NADH dehydrog 7 subunits >41 subunitsSuccinate CoQ red 0 subunits 4 subunitsCytochrome b-c1 comp 1 subunit 10 subunitsCytochrome C oxidase 3 subunits 10 subunitsATP synthase complex 2 subunits 14 subunitstRNA components 22 tRNAs nonerRNA components 2 components noneRibosomal proteins none ~80 Other mt proteins none mtDNA pol, RNA pol

etc.

Organization of the human genome

• Nuclear genome– 3300 Mb– 23 (XX) or 24 (XY) linear chromosomes– 65-80,000 genes– 1 gene/40kb– Introns– 3% coding– Repetitive DNA sequences (45%)– Recombination – Mendelian inheritance (X + auto, paternal Y)

Organization of the human genome

• Contrasting gene densities–HLA high density–Dystrophin low density

Organization of the human genome

• Gene families–Functionally similar genes are occasionally

clustered, but usually dispersed throughout the genome

Organization of the human genome

• Genes vary in size and exon content

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Organization of the human genome

• Genes within genes–Intron 26 of the NF1 gene contains three

internal genes.

Organization of the human genome

• Gene families defined by conserved amino acid motifs–DEAD box.–WD repeat families

Organization of the human genome

• Ig superfamily–Cell surface receptors–Similar domain structure

Organization of the human genome

• Clustered gene familiesGrowth hormone 5 copies (67kb)

globin 7 copies (50kb)

Hox genes (multi) 38 four clusters

Olfactory receptors 1000 in 25 large clusters

Organization of the human genome

• Interspersed gene familiesPax 9 copies

Actin >20 copies

Alu elements (repeats) 1.1 million

LINE elements (L1) 200-500,000

Organization of the human genome

• HLA heavy chain gene cluster–Gene fragments–Pseudogenes–Truncated genes

Organization of the human genome

• Processed pseudogenes–Originate by reverse transcription–TPRT

Organization of the human genome

• Chromosomal location of repeats–telomere–Centromere–LINE elements (Alu Elements)–Minisatellites

Organization of the human genome

• Formation of higher order repeat units

Organization of the human genome

• Human transposable elements

Organization of the human genome

• Transposable elements with RNA intermediates–Endogenous retroviruses–Retrotransposons–Retropseudogenes

Organization of the human genome

• Human transposable elements–Alu elements–LINE elements

Organization of the human genome

• Mobile elements and gene structure–RB1 region

• Alu• LINE• Simple sequence repeats