Genetica umana - evoluzione della specie - Appunti

Risultati

108061 agcacagacc tgggggtcac cgtaaaggtg gagcagcatt cccctaagca cagaggttgg

108121 ggccactgcc tggctttgtg acaactcggg gcgcatcaac ggtgaataaa atctttcccg

108181 gttgcagccg tgaataatca aggttagaga ccagttagag cggttcagtg cggaaaacgg

108241 gaaagaaaaa gcccctctga atcctgggca gcgagattct cccaaagcaa ggcgaggggc

108301 tgcattgcag ggtgagggtg agggttaggg tttgggttgg gtttggggtt ggggttgggg

108361 taggggtggg gttggggttg gggttggggt taggggtagg ggtaggggta ggggtagggt

108421 cagggtcagg gtcagggtta gggttttagg gttaggattt tagggttagg gtaagggtta

108481 agggttgggg ttggggttag ggttaggggt tagggttggg gttggggttg gggttggggt

108541 tggggttggg gttagggtta gctaaaccta accctaaccc ctaaccccaa ccccaacccc

108601 aaccctaccc ctacccctac ccctaacccc aacccccacc cttaaccctt aacccttacc

108661 ctaaccctaa cccaaaccct aaccctaccc taaccctaac ccaaccctaa ccctaaccct

108721 accctaaccc taacacccta aaaccgtgac cctgaccttg accctgaccc ttaaccctta

108781 accctaacca taaccctaaa ccctaaccct aaaccctaac cctaaaccct aaccctaaca

108841 ctaccctacc ctaaccccaa cccctaaccc ctaaccctaa

ccctacccct aaccccaacc108901 ccagccccaa cccttaccct aaccctaccc taacccttaa ccctaacccc taaccctaac108961 ccctaaccct aaccctaccc caaccccaaa cccaacccta acccaaccct aacccctaac109021 cctaacccct accctaaccc ctagccctag ccctagccct aaccctaacc ctcgccctaa109081 ccctcaccct aaccctcacc ctcaccctaa cccaacgtct gtgctgagaa gaatgctgct109141 ccgcctttaa ggtgcccccc aggtctgtgc tgaacagaac gcagctccgc cgtcgcagtg109201 ccctcagccc gcccgcccgg gtctgacctg agaagaactc tgctccgcct tcgcaatagc109261 cccgaagtct gtgcagagga gaacgcagct ccgccctcgc gatgctctcc ggctgtgtgc109321 taaagagaac gcaactccgc cctcgcaaag gcggcgcgcc ggcggaggcg cggagaggcg

RISULTATI108061 agcacagacc tgggggtcac cgtaaaggtg gagcagcatt cccctaagca cagaggttgg108121 ggccactgcc tggctttgtg acaactcggg gcgcatcaac ggtgaataaa atctttcccg108181 gttgcagccg tgaataatca aggttagaga ccagttagag cggttcagtg cggaaaacgg108241 gaaagaaaaa gcccctctga atcctgggca gcgagattct cccaaagcaa ggcgaggggc108301 tgcattgcag ggtgagggtg agggttaggg tttgggttgg gtttggggtt ggggttgggg HEAD108361 taggggtggg gttggggttg

gggttggggt taggggtagg ggtaggggta ggggtagggt 13108421 cagggtcagg gtcagggtta gggttttagg gttaggattt tagggttagg gtaagggtta108481 agggttgggg ttggggttag ggttaggggt tagggttggg gttggggttg gggttggggt108541 tggggttggg gttagggtta gctaaaccta accctaaccc ctaaccccaa ccccaacccc108601 aaccctaccc ctacccctac ccctaacccc aacccccacc cttaaccctt aacccttacc108661 ctaaccctaa cccaaaccct aaccctaccc taaccctaac ccaaccctaa ccctaaccct108721 accctaaccc taacacccta aaaccgtgac cctgaccttg accctgaccc ttaaccctta

accctaacca taaccctaaa ccctaaccct aaaccctaac cctaaaccct aaccctaaca 12108841 ctaccctacc ctaaccccaa cccctaaccc ctaaccctaa ccctacccct aaccccaacc108901 ccagccccaa cccttaccct aaccctaccc taacccttaa ccctaacccc taaccctaac108961 ccctaaccct aaccctaccc caaccccaaa cccaacccta acccaaccct aacccctaac109021 cctaacccct accctaaccc ctagccctag ccctagccct aaccctaacc ctcgccctaa109081 ccctcaccct aaccctcacc ctcaccctaa cccaacgtct gtgctgagaa gaatgctgct109141 ccgcctttaa ggtgcccccc aggtctgtgc tgaacagaac gcagctccgc cgtcgcagtg109201

ccctcagccc gcccgcccgg gtctgacctg agaagaactc tgctccgcct tcgcaatagc109261 cccgaagtct gtgcagagga gaacgcagct ccgccctcgc gatgctctcc ggctgtgtgc109321 taaagagaac gcaactccgc cctcgcaaag gcggcgcgcc ggcggaggcg cggagaggcgPERCHE' IL CAMBIO?108361 taggggtggg gttggggttg gggttggggt taggggtagg ggtaggggta ggggtagggt HEAD108421 cagggtcagg gtcagggtta gggttttagg gttaggattt tagggttagg gtaagggtta 13108481 agggttgggg ttggggttag ggttaggggt tagggttggg gttggggttg gggttggggt108541 tggggttggg gttagggtta gctaaaccta accctaaccc ctaaccccaa ccccaacccc HEAD108601 aaccctaccc ctacccctac ccctaacccc aacccccacc cttaaccctt aacccttacc108661 ctaaccctaa cccaaaccct aaccctaccc taaccctaac ccaaccctaa ccctaaccct 12108721 accctaaccc taacacccta aaaccgtgac cctgaccttg accctgaccc ttaaccctta(circa 37 ttaggg repeats nel Head 13; circa 88 ccctaa repeats nel Head 12)Perché dei TANDEM REPEATS sono cambiatittaggg a ccctaada ?EvoluzioneHomo SapiensCromosomi minidi- OInversioneHuman Chromosome #2 shows the exactpoint at which this

Fusion took place: "Chromosome 2 is unique to the human lineage of evolution, having emerged as a result of head-to-head fusion of two acrocentric chromosomes that remained separate in other primates. The precise fusion site has been located in 2q13-2q14.1 (ref. Inactivated 2; hg 16:114455823-114455838), where our centromere analysis confirmed the presence of multiple subtelomeric duplications to chromosomes 1, 5, 8, 9, 10, 12, 19, 21 and 22 (Fig. 3; Supplementary Fig. 3a, region A). During the formation of human chromosome 2, one of the two centromeres became inactivated (2q21, which corresponds to the centromere from chimp chromosome 13) and the centromeric structure quickly deterioriated Chr 2 (42)." Hillier et al (2005) "Generation and Annotation of the DNA sequences of human chromosomes 2 and 4," Nature 434: 724-731.

Recent Duplication Architecture of the Human Genome

12345678 200 Mb 250 Mb

91011 •Total: 5.26% (150.8

Mb)12 •Inter: 2.36% (67.6 Mb)1314 •Intra: 3.87% (111.1 Mb)15 •Non-random distribution16 •5.3 fold bias to pericentromere1718 •389 regions > 100 kb nexi19 “Heterochromatic” regions2021 Duplications22X 10 MbY 50 Mb 150 Mb100 Mb 2p2210q26 11p152p11 (700 kb) 11q14 11q14 7q3622q1221q21 4p16.14p16.112q24Xq28 4p16.312p11 4q24 7q36Alpha Satellite ( build34, >90%, >1kb)At the genome level

1. Structural variations
2. Segmental duplication

Inversions

• Human and chimp chromosomes
• Inversion between p14.1 and q14.1
• 9 total inversions in human vs. chimp
• Chromosome 3 very similar but orangutans have a large inversion
• May have established orangutans as a new species chromosomal fusion in the human lineage ?

Comparison of chimpanzee and human Y chromosomes. JF Hughes et al. Nature 000, 1-4 (2010)

Segmental duplication (impact: 2.7 %)

Longer than 20 kilobases (-> 300 kb), greater than 94 % sequence identity

• 33% of human duplicated segments are

human specific- 17 % of chimp duplication are chimp specific.

Half of the genes in the human specific duplicated regions exhibit significant differences in gene expression relative to chimp and are most often upregulated. Cheng et al., Nature (2005)

About 300 region were identified where the human genome showed significant increase in copy number when compared to chimp. 'Only' 92 regions where the chimp genome showed an increase in copy number compared to human (but with higher rate of duplication) Cheng et al., Nature (2005)

Evoluzione

Homo Sapiens

Cromosomi minidi- O

Cladogramma dei Primati

basato sui riarrangiamenti Cromosomici

La comparazione di sequenze di DNA indica il grado di correlazione evoluzionistica.

Il cariotipo tra le grandi scimmie differisce per eventi di inversione.

Il cariotipo tra le grandi scimmie e altri primati differisce soprattutto per eventi di traslocazioni.

Tutti i cromosoma X nei mammiferi hanno le stesse bande.

At the genome level

1) Structural variations

2) Segmental

1. Interspersed/Transposable repeats
   • The human genome is composed of ~ 45 % of interspersed elements
   • Including:
     • Long interspersed elements (LINEs); these encode a reverse transcriptase
     • Short interspersed elements (SINEs); these include Alu repeats
2. The human genome contains about 1,000,000 Alu elements.
3. Found only in primates.
4. Interspersed/Transposable element insertions (impact 3 %)
   • Endogenous mutagens which can alter genes, promote genomic rearrangements…
   • May help to drive the speciation of organisms
   • Particular interest in recently mobilized transposons
   • The transposons that inserted into human or chimp genome during the passed 6mo years would be expected to be present in only one of the 2 genome.
   • ~11’000 ‘recent’ transposons copies that are differentially present in human/chimp:
     • 73 % found in human and 27 % found in chimp
5. Interspersed/Transposable element insertions
   • Endogenous retrovirus Mills et al., Am. J. Hum. Genet., 78:671-679, 2006

At the sequence

level(coding sequence level)

At the gene level: 13’454 pair of orthologous genes (507 Swiss-Prot, 1134 TrEMBL: 1641) (NCBI: 3111) - 29 % are 100 % identical - 5% with in-frame indel (mainly in repetitive region)

La comparazione di sequenze di DNA indicano il grado di correlazione evoluzionistica.

La comparazione di sequenze di DNA indicano il grado di correlazione evoluzionistica.

Percentuale di bande cromosomiche condivise tra l’uomo e altre specie

Scimpanze 99+ %

Gorilla 99+ % Le bande sono molto conservate

Orang-utan 99+ % tra l’uomo e le African green monkey 95% grandi scimmie.

Gatto 35%

Topo 7%

Percentuale di differenza nella sequenza nucleotidica

Human-chimp 1.0%

Human-gorilla 2.3%

Human-orangutan 3.7%

Human-human 0.1%

Effetto “Bottleneck” ed evoluzione umana

• Si ritiene che la specie umana abbia avuto inizio da una popolazione sottoposta ad un effetto “bottleneck” circa 100.000 anni fa. Si ritrova un numero maggiore di variazioni genetiche tra scimpanzè

che vivono nell'Africa Centrale a 50 km di distanza che nell'intera specie umana. • Il grafico rappresenta le differenze mutazionali nel DNA mitocondriale tra vari membri delle grandi scimmie e l'uomo. The Chicken And The Egg 80 million years Amniotic Egg 330 million years Il Genoma dello Scimpanzè 98.5% in comune con il genoma umano. - 35 milioni di sostituzioni di un singolo nucleotide - 5 milioni di piccole inserzioni e delezioni - riarrangiamenti locali - 1 fusione cromosomica • I cani hanno circa lo 0.15% variazione genomica ma una grande differenza fenotipica • Mus musculus e mus spretus hanno tra loro la stessa differenza che esiste tra uomo e scimpanzè, ma una piccola differenza fenotipica Quantifying the sequence divergence: Single nucleotide substitutions: 1.23% (1, 78% for chromosome Y) (0.8 % in protein coding region) Indels: ~1.5 % Transposable elements: 3 % Recent duplication of DNA segments: 2.7 % ~ 35 mo nucleotides differences ~ 5 mo indels Manychromosomal rearrangements Human: 3.4 × 10⁹ bp; Chimp: 3.6 × 10⁹ bp Animal Connection
• L'uomo condivide molti fenotipi con gli animali
• Siamo molto simili alle altre specie