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Evoluzione del genoma
Lezione 22
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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.
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Il genoma umano
Quanti geni nell’uomo?
Nature Genetics 7:345 -346, 1994
Geni: 60.000 -70.000
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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?
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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)
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amphioxus
Nature, June 19, 2008
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]
VERTEBRATES
Evolution by gene duplication
Springer -Verlag. Berlin. 1970
“natural selection merely modifies,
while redundancy creates”
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I geni Hox
(chr. 2, 7, 12, 17)
Gene
Duplications
(four clusters)
Amphioxus
Hypothetical
Common
Ancestor
Drosophila
lab
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pb
Dfd
Scr
Antp
Ubx
AbdA
AbdB
Geni per i recettori olfattivi
circa 1000
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Destino dei geni duplicati
2
3
Duplication 1
sub
functionalization
1
loss
2
neo
function
non
functional
3
more enzyme activity
(amylase)
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Duplication2
1
I geni delle globine
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PNAS 105:1590 -5, 2008
Evolution by gene duplication
Springer -Verlag. Berlin. 1970
“natural selection merely modifies,
while redundancy creates”
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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
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perfezione
=
nessuna prospettiva
evolutiva
~ il 98% delle
specie che sono
esistite sulla terra
si sono estinte
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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
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SD (in om ozigosi)
CNV
Assenza di dati
per questioni tecniche
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DNA da testare
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DNA da testare
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Duplicazioni segmentali
comparazione uomo-scimpanze'
- comuni: 66% (79.8Mb)
- scimpanze'-specifiche (11.4Mb)
- umano-specifiche: 33% (26.5Mb)
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Nature 444:444-454 (2006).
Nature 453:56-64 (2008).
Differenza media fra 2 individui: circa 20.000.000 bp
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Il significato?
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plasticity
=
variability
=
evolution
perfezione
=
nessuna prospettiva
evolutiva
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fixed CNV (SD)
CNV
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fixed CNV (SD)
CNV
after meiosis
before checkpoint
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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.
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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.
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Science 320: 539 -543, 2008
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Am J Hum Genet 81: 1057-1069, 2007
Nature Genet 40:1076-1083, 2008.
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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
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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
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