Eukaryotic Genome Organization
EUKARYOTIC GENOME ORGANIZATION......................................................................................................... 1
CHROMOSOMES........................................................................................................................................... 3
HISTONE PROTEINS:..................................................................................................................................................3
NON-HISTONE PROTEINS:..........................................................................................................................................3
NUCLEOSOMES:.......................................................................................................................................................3
LEVELS OF CHROMOSOMAL COMPACTION:....................................................................................................................4
RADIAL LOOP-SCAFFOLD COMPACTION:.......................................................................................................................4
KARYOTYPE..............................................................................................................................................................4
Use:.................................................................................................................................................................4
SPECIALISED ELEMENTS OF CHROMOSOMES...................................................................................................................4
1. Origins of replication:..................................................................................................................................5
2. Telomeres:...................................................................................................................................................5
3. Centromeres:...............................................................................................................................................5
HETEROCHROMATIN..................................................................................................................................................5
EUCHROMATIN.........................................................................................................................................................6
CHROMOSOMAL REARRANGEMENTS............................................................................................................ 6
CHROMOSOMAL DELETIONS.......................................................................................................................................6
CHROMOSOMAL DUPLICATIONS..................................................................................................................................6
SUMMARY: HOW DUPLICATIONS & DELETIONS AFFECT PHENOTYPE...................................................................................7
CHROMOSOMAL INVERSIONS......................................................................................................................................7
CHROMOSOMAL TRANSLOCATIONS..............................................................................................................................7
Reciprocal Translocation:................................................................................................................................8
Unbalanced reciprocal translocation:........................................................................................................................8
ANEUPLOIDY............................................................................................................................................................8
EXTRA-NUCLEAR DNA................................................................................................................................... 8
INTRODUCTION TO EXTRA-NUCLEAR INHERITANCE..........................................................................................................8
MITOCHONDRIAL DNA (MTDNA)..............................................................................................................................9
Structure:........................................................................................................................................................9
Yeast mtDNA genome:....................................................................................................................................9
Plant mtDNA genome:....................................................................................................................................9
Mitochondrial DNA Genetic Diseases:............................................................................................................9
Range of severity of phenotypes:............................................................................................................................10
Mitochondrial inheritance in identical twins:...............................................................................................10
Mechanism of uniparental inheritance:.......................................................................................................10
EXTRA-NUCLEAR DNA AS A EVOLUTIONARY MOLECULAR MARKER..............................................................10
ENDOSYMBIONT THEORY: ORIGIN OF ORGANELLE GENOMES..........................................................................................10
Evidence:.......................................................................................................................................................11
MTDNA/CPDNA RATE OF MUTATION.......................................................................................................................11
MITOCHONDRIAL ‘EVE’...........................................................................................................................................11
Fossil Evidence:.............................................................................................................................................11
MULTI-REGIONAL HYPOTHESIS (BEFORE MTDNA THEORIES)..........................................................................................11
OUT-OF-AFRICA HYPOTHESIS (BEFORE MTDNA THEORIES)...........................................................................................12
PHYLOGENETIC TREES..............................................................................................................................................12
........................................................................................................................................................................ 13
CANN, STONEKING & WILSON MTDNA STUDIES.........................................................................................................14
Results:..........................................................................................................................................................14
THE GENETIC ANALYSIS OF POPULATIONS AND HOW THEY EVOLVE.............................................................14
IMPORTANT POPULATION GENETIC TERMS...................................................................................................................14
CALCULATING ALLELE FREQUENCIES...........................................................................................................................15
The Hardy-Weinberg law..............................................................................................................................15
FOUNDER EFFECTS & POPULATION BOTTLENECKS.........................................................................................................16
Founder effects:............................................................................................................................................16
1
,Eukaryotic Genome Organization
Population bottlenecks:................................................................................................................................16
NATURAL SELECTION ALTERS ALLELE FREQUENCIES........................................................................................................16
VIOLATIONS OF A HWE ASSUMPTION:.......................................................................................................................16
Mating is NOT random:................................................................................................................................16
There IS Selection:.........................................................................................................................................17
EXAMPLES OF SELECTION.........................................................................................................................................17
Evolution of pesticide resistance:..................................................................................................................17
Evolution of bacterial resistance:..................................................................................................................17
Populations NOT infinitely large (RANDOM GENETIC DRIFT (RGD))............................................................17
2
, Eukaryotic Genome Organization
Chromosomes
- Each chromosome packages a single long mol of DNA
- Comprised of chromatin (DNA & protein)
- Chromatin consists of 1/3 DNA; 1/3 histone protein, 1/3 non-histone protein
- DNA is packaged into chromosomes because the human genome is to big so needs
to be compressed.
Histone Proteins:
- Small basic, positively charged amino acids (lysine & arginine) = ~ half all chromatin
protein weight
- Histones bind & neutralize negatively charged DNA
- 5 types of histone: H1, H2A, H2B, H3, H4
o H2-4 = core histones – form nucleosome
o Linker histone (H1) joins histones to form the nucleosome
- High level of sequence conservation of histones among diverse organisms.
Non-Histone Proteins:
- Large variety (200-2,000,000) of non-histone proteins
- Therefore have large variety of functions:
o Scaffolding: backbone of chromosome (aid the compaction of chromosome)
o DNA replication: e.g. DNA polymerase
o Chromosome segregation: e.g. motor proteins of kinetochores
o Transcriptional regulation: transcription factors are largest group, regulate
transcription during gene expression (5000 – 10 000 different transcription
factors)
- Occur in different amounts in different tissues
Nucleosomes:
- Fundamental unit of chromosome packaging
- Condensed DNA form chromatin fibres (string) with beads (nucleosomes)
- Have diameter of ±100 Â (Â = Angstrom = 10-10m); chromatin fibres have diameter of
20Â
- Each nucleosome = ~160bp of DNA wrapped twice around a core of 8 histones
- Nucleosome spacing is an important function and is inherited to daughter cells.
- Linker DNA links together nucleosomes & is about 40bp of DNA
- DNA sequence, spacing & structure affect genetic function
3
EUKARYOTIC GENOME ORGANIZATION......................................................................................................... 1
CHROMOSOMES........................................................................................................................................... 3
HISTONE PROTEINS:..................................................................................................................................................3
NON-HISTONE PROTEINS:..........................................................................................................................................3
NUCLEOSOMES:.......................................................................................................................................................3
LEVELS OF CHROMOSOMAL COMPACTION:....................................................................................................................4
RADIAL LOOP-SCAFFOLD COMPACTION:.......................................................................................................................4
KARYOTYPE..............................................................................................................................................................4
Use:.................................................................................................................................................................4
SPECIALISED ELEMENTS OF CHROMOSOMES...................................................................................................................4
1. Origins of replication:..................................................................................................................................5
2. Telomeres:...................................................................................................................................................5
3. Centromeres:...............................................................................................................................................5
HETEROCHROMATIN..................................................................................................................................................5
EUCHROMATIN.........................................................................................................................................................6
CHROMOSOMAL REARRANGEMENTS............................................................................................................ 6
CHROMOSOMAL DELETIONS.......................................................................................................................................6
CHROMOSOMAL DUPLICATIONS..................................................................................................................................6
SUMMARY: HOW DUPLICATIONS & DELETIONS AFFECT PHENOTYPE...................................................................................7
CHROMOSOMAL INVERSIONS......................................................................................................................................7
CHROMOSOMAL TRANSLOCATIONS..............................................................................................................................7
Reciprocal Translocation:................................................................................................................................8
Unbalanced reciprocal translocation:........................................................................................................................8
ANEUPLOIDY............................................................................................................................................................8
EXTRA-NUCLEAR DNA................................................................................................................................... 8
INTRODUCTION TO EXTRA-NUCLEAR INHERITANCE..........................................................................................................8
MITOCHONDRIAL DNA (MTDNA)..............................................................................................................................9
Structure:........................................................................................................................................................9
Yeast mtDNA genome:....................................................................................................................................9
Plant mtDNA genome:....................................................................................................................................9
Mitochondrial DNA Genetic Diseases:............................................................................................................9
Range of severity of phenotypes:............................................................................................................................10
Mitochondrial inheritance in identical twins:...............................................................................................10
Mechanism of uniparental inheritance:.......................................................................................................10
EXTRA-NUCLEAR DNA AS A EVOLUTIONARY MOLECULAR MARKER..............................................................10
ENDOSYMBIONT THEORY: ORIGIN OF ORGANELLE GENOMES..........................................................................................10
Evidence:.......................................................................................................................................................11
MTDNA/CPDNA RATE OF MUTATION.......................................................................................................................11
MITOCHONDRIAL ‘EVE’...........................................................................................................................................11
Fossil Evidence:.............................................................................................................................................11
MULTI-REGIONAL HYPOTHESIS (BEFORE MTDNA THEORIES)..........................................................................................11
OUT-OF-AFRICA HYPOTHESIS (BEFORE MTDNA THEORIES)...........................................................................................12
PHYLOGENETIC TREES..............................................................................................................................................12
........................................................................................................................................................................ 13
CANN, STONEKING & WILSON MTDNA STUDIES.........................................................................................................14
Results:..........................................................................................................................................................14
THE GENETIC ANALYSIS OF POPULATIONS AND HOW THEY EVOLVE.............................................................14
IMPORTANT POPULATION GENETIC TERMS...................................................................................................................14
CALCULATING ALLELE FREQUENCIES...........................................................................................................................15
The Hardy-Weinberg law..............................................................................................................................15
FOUNDER EFFECTS & POPULATION BOTTLENECKS.........................................................................................................16
Founder effects:............................................................................................................................................16
1
,Eukaryotic Genome Organization
Population bottlenecks:................................................................................................................................16
NATURAL SELECTION ALTERS ALLELE FREQUENCIES........................................................................................................16
VIOLATIONS OF A HWE ASSUMPTION:.......................................................................................................................16
Mating is NOT random:................................................................................................................................16
There IS Selection:.........................................................................................................................................17
EXAMPLES OF SELECTION.........................................................................................................................................17
Evolution of pesticide resistance:..................................................................................................................17
Evolution of bacterial resistance:..................................................................................................................17
Populations NOT infinitely large (RANDOM GENETIC DRIFT (RGD))............................................................17
2
, Eukaryotic Genome Organization
Chromosomes
- Each chromosome packages a single long mol of DNA
- Comprised of chromatin (DNA & protein)
- Chromatin consists of 1/3 DNA; 1/3 histone protein, 1/3 non-histone protein
- DNA is packaged into chromosomes because the human genome is to big so needs
to be compressed.
Histone Proteins:
- Small basic, positively charged amino acids (lysine & arginine) = ~ half all chromatin
protein weight
- Histones bind & neutralize negatively charged DNA
- 5 types of histone: H1, H2A, H2B, H3, H4
o H2-4 = core histones – form nucleosome
o Linker histone (H1) joins histones to form the nucleosome
- High level of sequence conservation of histones among diverse organisms.
Non-Histone Proteins:
- Large variety (200-2,000,000) of non-histone proteins
- Therefore have large variety of functions:
o Scaffolding: backbone of chromosome (aid the compaction of chromosome)
o DNA replication: e.g. DNA polymerase
o Chromosome segregation: e.g. motor proteins of kinetochores
o Transcriptional regulation: transcription factors are largest group, regulate
transcription during gene expression (5000 – 10 000 different transcription
factors)
- Occur in different amounts in different tissues
Nucleosomes:
- Fundamental unit of chromosome packaging
- Condensed DNA form chromatin fibres (string) with beads (nucleosomes)
- Have diameter of ±100 Â (Â = Angstrom = 10-10m); chromatin fibres have diameter of
20Â
- Each nucleosome = ~160bp of DNA wrapped twice around a core of 8 histones
- Nucleosome spacing is an important function and is inherited to daughter cells.
- Linker DNA links together nucleosomes & is about 40bp of DNA
- DNA sequence, spacing & structure affect genetic function
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