Cytogenetic and molecular characterization of the macro- and micro-inversions, which distinguish the human and the chimpanzee karyotypes [Elektronische Ressource] : from speciation to polymorphism / presented by Justyna Monika Szamalek

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• Publié par: universitat_ulm
• Publié le: 01 janvier 2006
• Nombre de lectures: 23
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

University of Ulm
Department of Human Genetics
Prof. Dr. med. Walther Vogel





Cytogenetic and Molecular Characterization of the Macro- and
Micro-inversions, which Distinguish the Human and the
Chimpanzee Karyotypes - from Speciation to Polymorphism




Thesis
Applying for the Degree of Doctor of Human Biology (Dr. hum. biol.)
Faculty of Medicine
University of Ulm





Presented by
Justyna Monika Szamalek
from Września in Poland




2006
Amtierender Dekan: Prof. Dr. Klaus-Michael Debatin
1. Berichterstatter: Prof. Dr. med. Horst Hameister
2. Berichterstatter: Prof. Dr. med. Konstanze Döhner
Tag der Promotion: 28.07.2006

Content
Content

1. Introduction ...................................................................................................................7
1.1. Primate phylogeny........................................................................................................7
1.2. Africa as the place of human origin and the living area
of the present-day chimpanzee populations .................................................................9
1.3. Cytogenetic and molecular differences between human
and chimpanzee genomes.............................................................................................10
1.4. Cytogenetic and molecular differences between common
chimpanzee and bonobo genomes ................................................................................17
1.5. Theory of speciation .....................................................................................................18
1.6. Theory of selection .......................................................................................................20
1.7. Aims of the work presented in this thesis.....................................................................21

2. Materials and Methods .................................................................................................22
2.1. Materials .......................................................................................................................22
2.2. Methods ........................................................................................................................36

3. Results.............................................................................................................................47
3.1. Characterization of the chimpanzee lineage-specific
pericentric inversion of chromosome 5 .........................................................................47
3.2. Characterization of the human lineage-specific
pericentric inversion of chromosome 1 .........................................................................54
3.3. Verification of identity of the chimpanzee-specific
pericentric inversions between Pan troglodytes and Pan paniscus..............................66
3.4. Determination of the human-chimpanzee DNA
divergence rate within inverted and collinear regions..................................................71
3.5. Genome-wide search for micro-inversions
by gene order comparison between human and chimpanzee .......................................75

4. Discussion .......................................................................................................................84
4.1. Comparison of the pericentric inversions of chromosomes 1 and 5.............................84
4.2. Determination of the time interval within which the chimpanzee
lineage-specific inversions became introduced ..........................................................89
4.3. Testing of the chromosomal speciation theory.............................................................90
3 Content
4.4. Micro-inversions as a newly discovered class of
human-chimpanzee divergence ....................................................................................94
4.5. Inversions and their influence on neighbouring genes .................................................97
4.6. Conclusions ..................................................................................................................99

5. Summary ..................................................................................................................... 101

6. References.................................................................................................................... 103

7. Appendix ..................................................................................................................... 118

8. Acknowledgements ..................................................................................................... 131

9. Curriculum vitae ........................................................................................................ 132


4 Abbreviations
Abbreviations

aCGH Array based comparative genomic hybridization
AIDS Acquired immune deficiency syndrome
Alu Short stretch of DNA characterized by the action of the Alu restriction
endonuclease isolated from Arthrobacter luteus
BAC F-factor-based bacterial artificial chromosome
bp Base pair
BSA Bovine serum albumin
CCD Charge-coupled device
CND Copy number difference
CNV Copy number variation
CNP Copy number polymorphism
DAPI 4,6 Diamidino-2-phenylindole
DC Duplication cluster
DNA Deoxyribonucleic acid
dNTP Deoxyribonucleotide triphosphate
dUTP Deoxyuridine triphosphate
EBV Epstein-Barr virus
EDTA Ethylene diaminetetraacetic acid
ERV Endogenous retroviral sequences
F1 First filial generation, in Mendelian genetics means the hybrid offspring
of purebred parental generation
FCS Fetal calf serum
FISH Florescence in situ hybridization
FITC Fluorescein isothiocyanate
GGO Gorilla gorilla (Gorilla)
HSA Homo sapiens (Human)
HERV-K Human endogenous retrovirus K
ISCN International System for Human Cytogenetic Nomenclature
kb Kilobase
L1 Family of long transposable sequences belonging to LINEs
LCR Low copy repeat
LINE Long interspersed nuclear elements
5 Abbreviations
LTR Long terminal repeat
Mb Megabase
MFA Macaca fascicularis (Macaque)
Mya Million years ago
NAHR Non-allelic homologous recombination
NHEJ Non-homologous end joining
PAC P1-derived artificial chromosome
PBS Phosphate buffered saline solution
PCR Polymerase chain reaction
PHA Phytohemagglutinin, an initiator of mitosis
PPA Pan paniscus (Bonobo)
PPY Pongo pygmaeus (Orangutan)
PtERV Pan troglodytes endogenous retrovirus
PTR Pan troglodytes (Common chimpanzee)
RT Room temperature
SD Segmental duplication
SDS Sodium dodecyl sulfate
SINE Short interspersed nuclear elements
SSC Saline sodium citrate solution
TE Tris-EDTA
Tris Tris (hydroxymethyl) aminomethane
6 Introduction
1. Introduction

It was postulated by Goodman in 1999 that, if the taxonomic classification were
based exclusively upon genomic DNA sequence similarity, the nearly 99% identity of
human, chimpanzee and bonobo genomes would require a reclassification of the latter two
into the genus Homo. However, whereas there are many similarities in the biology, life
history, and the behaviour of humans and great apes there are also many striking variations
that need to be explained. The mostly recognized and often mentioned differences are the
bipedalism and the developed speech, which are exclusive to humans, but also differences
in susceptibility to diseases such as AIDS or malaria, and above all the large brain size and
extended cognitive capacities that unique human characteristics (reviewed in Olson and
Varki 2003; Carroll 2003; Varki and Altheide 2006).

1.1. Primate phylogeny

More than 300 species of over 60 genera were classified as extant members of the
order Primates. The data obtained from comparative sequencing approaches suggest that
Primates divide into the Strepsirrhini (e.g. lemurs, lorises), the Tarsiiformes (tarsiers) and
the Anthropoidea. The letter ones split into the Platyrrhini, which are represented by New
World monkeys, and the Catarrhini that consist of Old World monkeys and apes
(Hominoidea) (Goodman et al. 2005; Figures 1 and 2). The story of the hominoid
taxonomy is one of gradual demotion of humans from a special position in the taxonomy to
being one branch among many. Although according to the modern taxonomy, based on the
genetic similarities, humans are included in the group of apes, in this work I will refer to
humans and great apes or African great apes separately, in the now colloquial sense
(Figure 1). The close evolutionary relationship of humans with the African great apes i.e.
chimpanzees and gorillas was posited already more than 100 years ago (Darwin 1871;
Huxley 1863). In the traditional theory based on anatomical and mental differences
between these species, the chimpanzees and the gorillas were grouped closer to the
orangutans rather then to humans. In fact, there is already convincing DNA sequence
evidence, that not only are chimpanzees and gorillas more closely related to humans than