Organization of the human genome Genome structure Nuclear

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 – r. RNA, t. RNA 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 genomes NADH dehydrog Succinate Co. Q red Cytochrome b-c 1 comp Cytochrome C oxidase ATP synthase complex t. RNA components r. RNA components Ribosomal proteins Other mt proteins mt encoded nuclear 7 subunits 0 subunits 1 subunit 3 subunits 22 t. RNAs 2 components none >41 subunits 4 subunits 10 subunits 14 subunits none ~80 mt. DNA 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/40 kb – 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 NF 1 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 families Growth hormone aglobin Hox genes (multi) Olfactory receptors 5 copies (67 kb) 7 copies (50 kb) 38 four clusters 1000 in 25 large clusters

Organization of the human genome • Interspersed gene families Pax Actin Alu elements (repeats) LINE elements (L 1) 9 copies >20 copies 1. 1 million 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 – RB 1 region • Alu • LINE • Simple sequence repeats