Evoluzione del genoma Lezione 22 By NA By NA Evoluzione questa sconosciuta Evoluzione cosa significa? in italiano: processo graduale attraverso il quale qualcosa si trasforma in altra piu’ complessa e/o migliore . E’ spesso considerato sinonimo di sviluppo. in biologia: cambiamenti nel pool genomico di una popolazione che nel corso delle generazioni, attraverso l’azione del caso e della selezione naturale portano alla nascita di nuove specie quindi non c’e’ un tendere verso qualcosa di migliore. Questo e’ quello che ha disturbato e continua a disturbare molti. By NA Il genoma umano Quanti geni nell’uomo? Nature Genetics 7:345 -346, 1994 Geni: 60.000 -70.000 By NA 2001 Completamento della sequenza del genoma umano cosa ci dice? Il numero di geni stimato nel genoma umano ~30.000 intesi come sequenze codificanti per proteine SNP’s:Eterozigosi media per il DNA genomico umano: ~0,0037 (0,37%). Cio’ significa che in due alleli circa 1:250-1:1000 basi sono diverse microsatelliti: variazioni di lunghezza del DNA identificabili PCR.... tutto finito? By NA via Duplicazioni di interi genomi Nat. Genet. 31(1):100 -105 (2002) Nat. Genet. 31(2):200 -204 (2002) Nat. Genet. 31(2):205 -209 (2002) By NA amphioxus Nature, June 19, 2008 By NA ] VERTEBRATES Evolution by gene duplication Springer -Verlag. Berlin. 1970 “natural selection merely modifies, while redundancy creates” By NA I geni Hox (chr. 2, 7, 12, 17) Gene Duplications (four clusters) Amphioxus Hypothetical Common Ancestor Drosophila lab By NA pb Dfd Scr Antp Ubx AbdA AbdB Geni per i recettori olfattivi circa 1000 By NA Destino dei geni duplicati 2 3 Duplication 1 sub functionalization 1 loss 2 neo function non functional 3 more enzyme activity (amylase) By NA Duplication2 1 I geni delle globine By NA PNAS 105:1590 -5, 2008 Evolution by gene duplication Springer -Verlag. Berlin. 1970 “natural selection merely modifies, while redundancy creates” By NA Nat Genet 39:1256-1260 (2007) Present in the saliva Starch digestion in the mouth 10 Hadza women (Tanzania) gathering tuberous Starch consumption is a prominent characteristic of agricultural societies Yakut horseman (Siberia) after hunting Rainforest and circum -arctic hunter-gatherers and some pastoralists consume much less starch. low ~5 high ~7 plasticity = variability = evolution By NA perfezione = nessuna prospettiva evolutiva ~ il 98% delle specie che sono esistite sulla terra si sono estinte By NA Lactase-phlorizin hydrolase (LPH) enzyme hydrolyzes lactose into glucose and galactose LPH declines rapidly after weaning. However, some individuals maintain the ability to digest milk and other dairy products into adulthood. Lactase persistency Early Neolithic cattle pastoralist Beja -Pereira et al. 2003 Lactase gene 3,9 kb iinsertion ( del) in the first intron 1 st intron in complete linkage disequilibrium with the single-nucleotide polymorphism that has been associated with lactase persistence In Europeans: 0.11% (0.86%) In Africans: 0.86% (0.11%) 1920 Nat Genet 2007, 39:31 -40 1271 By NA By NA SD (in om ozigosi) CNV Assenza di dati per questioni tecniche By NA DNA da testare By NA DNA da testare By NA By NA By NA By NA Duplicazioni segmentali comparazione uomo-scimpanze' - comuni: 66% (79.8Mb) - scimpanze'-specifiche (11.4Mb) - umano-specifiche: 33% (26.5Mb) By NA Nature 444:444-454 (2006). Nature 453:56-64 (2008). Differenza media fra 2 individui: circa 20.000.000 bp By NA By NA Il significato? By NA plasticity = variability = evolution perfezione = nessuna prospettiva evolutiva By NA fixed CNV (SD) CNV By NA fixed CNV (SD) CNV after meiosis before checkpoint By NA PNAS 104:10950 -5 (2007). … Finally, the high level of instability at the alpha-globin locus contrasts with the rarity in most populations of chromosomes carrying duplications or deletions, pointing to strong selective constraints that maintain alpha-globin gene copy number in human populations. By NA PNAS in press Li-Fraumeni syndrome is an autosomal dominantly inherited disorder characterized by a strikingly increased risk of early-onset breast cancer, sarcomas, brain tumors and other neoplasms in individuals harboring germline TP53 mutations. By NA By NA Science 320: 539 -543, 2008 By NA Am J Hum Genet 81: 1057-1069, 2007 Nature Genet 40:1076-1083, 2008. By NA Genome Research 2000 Yonggang J, Evan E. Eichler, Stuart Schwartz, and Robert D. Nicholls Structure of Chromosomal Duplicons and their Role in Mediating Human Genomic Disorders Genome Research Vol. 10, Issue 5, 597 -610, May 2000 Analysis of long stretches of available sequence from human chromosomes 22 and X suggest that 5% -10% of the genome may be duplicated (Mazzarella and Schlessinger 1998; Dunham et al. 1999). Sequence homology between duplicated DNA segments provides a chance for misalignment during meiosis, leading to unequal exchange and chromosome rearrangement, by either inter - or intrachromosomal or sister chromatid homologous recombination. This process with divergence between duplicated segments is essential to the generation of diversity and new genes over evolutionary time, although the more typical, shortterm effect is genetic disease. Variabilita’ ricchezza per la specie Variabilita’ problemi per i singoli By NA E’ la logica :le esigenze dei m olti contano di piu’ di quelle dei pochi o di uno Mr.Spock: Star Trek : L’ira di Khan By NA By NA