Chromosome Structure, Nucleosome Model & Variation in chromosome number, Chromosome Alterations Dr....
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Transcript of Chromosome Structure, Nucleosome Model & Variation in chromosome number, Chromosome Alterations Dr....
Chromosome Chromosome Structure, Structure, Nucleosome ModelNucleosome Model
& & Variation in Variation in chromosome number, chromosome number, Chromosome Chromosome AlterationsAlterations
Dr. Madhumita BhattacharjeeAssiatant ProfessorBotany Deptt.P.G.G.C.G. -11,Chandigarh
Chromosomes and Chromosomes and GeneticsGenetics
Basic review:Basic review: Chromosomes are long pieces of DNA, with Chromosomes are long pieces of DNA, with
supporting proteins.supporting proteins. Genes are short regions of this DNA that Genes are short regions of this DNA that
hold the information needed to build and hold the information needed to build and maintain the bodymaintain the body
Genes have fixed locations: each gene is in Genes have fixed locations: each gene is in a particular place on a particular chromosomea particular place on a particular chromosome
Diploids have 2 copies of each Diploids have 2 copies of each chromosome, one from each parent. This chromosome, one from each parent. This means 2 copies of each gene.means 2 copies of each gene.
The interactions between the 2 copies of The interactions between the 2 copies of each gene give rise to the various forms of each gene give rise to the various forms of dominance. dominance.
ChromosomesChromosomes
The essential part of a The essential part of a chromosome is a single very chromosome is a single very long strand of DNA. This DNA long strand of DNA. This DNA contains all the genetic contains all the genetic information for creating and information for creating and running the organism. running the organism.
Each chromosome has a Each chromosome has a central constricted region central constricted region called a called a centromerecentromere that serves that serves as an attachment point for the as an attachment point for the machinery of mitosis.machinery of mitosis.
ChromosomesChromosomes
Chromosomes exist in 2 different Chromosomes exist in 2 different states, before and after they states, before and after they replicate their DNA. Before replicate their DNA. Before replication, chromosomes have replication, chromosomes have one chromatid. After replication, one chromatid. After replication, chromosomes have 2 sister chromosomes have 2 sister chromatids, held together at the chromatids, held together at the centromere. Each centromere. Each chromatidchromatid is is one piece of DNA with its one piece of DNA with its supporting proteins. supporting proteins.
In mitosis, the two chromatids of In mitosis, the two chromatids of each chromosome separate, with each chromosome separate, with each chromatid going into a each chromatid going into a daughter cell.daughter cell.
Chromosomes = DNAChromosomes = DNA
Eukaryotic chromosomal Eukaryotic chromosomal organizationorganization
2 main groups of proteins involved in 2 main groups of proteins involved in folding/packaging eukaryotic folding/packaging eukaryotic chromosomeschromosomes HistonesHistones = positively charged proteins filled = positively charged proteins filled
with amino acids lysine and arginine that with amino acids lysine and arginine that bondbond
Nonhistones Nonhistones = less positive= less positive
Model for Chromatin Model for Chromatin StructureStructure
Chromatin is linked together every 200 bps Chromatin is linked together every 200 bps (nuclease digestion)(nuclease digestion)
Chromatin arranged like Chromatin arranged like ““String onBeads”String onBeads” (electron microscope) (electron microscope) 8 histones in each nucleosome8 histones in each nucleosome 147 bps per nucleosome core particle with 147 bps per nucleosome core particle with
53 bps for linker DNA (H1)53 bps for linker DNA (H1) Left-handed superhelixLeft-handed superhelix
Eukaryotic chromosomal Eukaryotic chromosomal organizationorganization
Histone proteinsHistone proteins AbundantAbundant Histone protein sequence is highly Histone protein sequence is highly
conserved among eukaryotesconserved among eukaryotes Provide the first level of packaging for the Provide the first level of packaging for the
chromosomechromosome DNA is wound around histone proteins to DNA is wound around histone proteins to
produce nucleosomes; stretch of unwound produce nucleosomes; stretch of unwound DNA between each nucleosomeDNA between each nucleosome
Eukaryotic chromosomal Eukaryotic chromosomal organizationorganization
Nonhistone proteinsNonhistone proteins Other proteins that are associated with the Other proteins that are associated with the
chromosomeschromosomes Many different types in a cell; highly variable in cell Many different types in a cell; highly variable in cell
types, organisms, and at different times in the same types, organisms, and at different times in the same cell typecell type
Amount of nonhistone protein variesAmount of nonhistone protein varies May have role in compaction or be involved in other May have role in compaction or be involved in other
functions requiring interaction with the DNAfunctions requiring interaction with the DNA Many are acidic and negatively charged; bind to the Many are acidic and negatively charged; bind to the
histones; binding may be transienthistones; binding may be transient
Eukaryotic chromosomal Eukaryotic chromosomal organizationorganization
Histone proteinsHistone proteins 5 main types5 main types
H1—attached to the nucleosome and involved in H1—attached to the nucleosome and involved in further compaction of the DNA (conversion of 10 further compaction of the DNA (conversion of 10 nm chromatin to 30 nm chromatin)nm chromatin to 30 nm chromatin)
H2AH2A H2BH2B H3H3 H4H4
This structure produces 10nm chromatinThis structure produces 10nm chromatin
Two copies in each nucleosome ‘histone octomer’; DNA wraps around this structure1.75 times
Nucleosome structureNucleosome structure
.
Nucleosomes connected together by linker DNA and Nucleosomes connected together by linker DNA and H1 histone to produce H1 histone to produce
the “beads-on-a-string” extended form of the “beads-on-a-string” extended form of chromatinchromatin
10 nm chromatin is produced in the first level of packaging.
Linker DNA
H1 Histone octomer
- Core DNA = 146 bp
- Linker DNA = 8-114 bp (usually 55bp)
- DNA turns 1 and ¾ times around histone octamer.
Types of Genetic variationTypes of Genetic variation
Allelic variationsAllelic variations mutations in particular genes (loci)mutations in particular genes (loci)
Chromosomal aberrationsChromosomal aberrations Changes in chromosome Number Changes in chromosome Number ( Numerical)( Numerical) Changes in chromosome Structure Changes in chromosome Structure (Structural)(Structural)
VARIATIONS IN VARIATIONS IN CHROMOSOME NumberCHROMOSOME Number
Variation In Chromosome Variation In Chromosome NumberNumber
EuploidyEuploidy Normal variations of the number of complete sets Normal variations of the number of complete sets
of chromosomesof chromosomes Haploid, Diploid, Triploid, Tetraploid, etc…Haploid, Diploid, Triploid, Tetraploid, etc…
AneuploidyAneuploidy Variation in the number of particular Variation in the number of particular
chromosomes within a setchromosomes within a set Monosomy, trisomy, polysomyMonosomy, trisomy, polysomy
VARIATIONS IN CHROMOSOME STRUCTURE VARIATIONS IN CHROMOSOME STRUCTURE (CHROMOSOMAL REARRANGEMENTS)(CHROMOSOMAL REARRANGEMENTS)
DeletionsDeletions Loss of a region of a chromosomeLoss of a region of a chromosome
DuplicationsDuplications InversionsInversions
Pericentric – inversion about the Pericentric – inversion about the centromerecentromere
Paracentric – inversion not involving the Paracentric – inversion not involving the centromerecentromere
TranslocationsTranslocations
Exchange or joining of regions of two non-Exchange or joining of regions of two non-homologous chromosomeshomologous chromosomes
Polyploidy v AneuploidyPolyploidy v Aneuploidy
8-51
Plants commonly exhibit polyploidyPlants commonly exhibit polyploidy 30-35% of ferns and flowering plants are polyploid30-35% of ferns and flowering plants are polyploid Many of the fruits & grain are polyploid plantsMany of the fruits & grain are polyploid plants
Polyploid strains often Polyploid strains often display desirabledisplay desirableagricultural agricultural characteristicscharacteristics wheatwheat cottoncotton strawberriesstrawberries bananasbananas large blossom flowerslarge blossom flowers
Euploidy VariationsEuploidy Variations
Each cell receives one copy of some
chromosomes
and two copies of other chromosomes
PolyploidyPolyploidy Polyploids with odd chromosome sets are usually sterilePolyploids with odd chromosome sets are usually sterile
produce mostly aneuploid gametesproduce mostly aneuploid gametes rare a diploid & haploid gamete are producedrare a diploid & haploid gamete are produced
Benefit of Odd Ploidy-Benefit of Odd Ploidy-Induced SterilityInduced Sterility
Seedless fruitSeedless fruit watermelons and bananaswatermelons and bananas asexually propagated by human via cuttingsasexually propagated by human via cuttings
Seedless flowersSeedless flowers Marigold flowering plantsMarigold flowering plants
Prevention of cross pollination of transgenic Prevention of cross pollination of transgenic plants plants
Generation of PolyploidsGeneration of Polyploids
AutopolyploidyAutopolyploidy Complete nondisjunction of both gametes can produce an Complete nondisjunction of both gametes can produce an
individual with one or more sets of chromosomesindividual with one or more sets of chromosomes
Interspecies Crosses can Generate AlloploidsInterspecies Crosses can Generate Alloploids
AlloploidyAlloploidy Offspring generally sterileOffspring generally sterile
An allotetraploid: Contains two
complete sets of chromosomes
from two different species
Interspecies Crosses Result in Interspecies Crosses Result in AlloploidsAlloploids
AllodiploidAllodiploid one set of chromosomes from two different speciesone set of chromosomes from two different species
AllopolyploidAllopolyploid combination of both autopolyploidy and alloploidy combination of both autopolyploidy and alloploidy
Experimental Treatments Can Promote Experimental Treatments Can Promote PolyploidyPolyploidy
Polyploid and allopolyploid plants often exhibit Polyploid and allopolyploid plants often exhibit desirable traitsdesirable traits
Colchicine is used to promote polyploidyColchicine is used to promote polyploidy
Colchicine binds to tubulin, disrupting microtubule Colchicine binds to tubulin, disrupting microtubule formation and blocks chromosome segregationformation and blocks chromosome segregation
Amount of genetic information in the chromosome Amount of genetic information in the chromosome can changecan change Deficiencies/DeletionsDeficiencies/Deletions DuplicationsDuplications
The genetic material remains the same, but is The genetic material remains the same, but is rearrangedrearranged InversionsInversions TranslocationsTranslocations
Variation In Chromosome StructureVariation In Chromosome Structure
A chromosomal deficiency occurs when a A chromosomal deficiency occurs when a chromosome breaks and a fragment is lostchromosome breaks and a fragment is lost
Deficiencies (Deletions)Deficiencies (Deletions)
Phenotypic consequences of deficiency depends onPhenotypic consequences of deficiency depends on Size of the deletionSize of the deletion Functions of the genes deletedFunctions of the genes deleted
Phenotypic effect of deletions usually detrimentalPhenotypic effect of deletions usually detrimental
DeficienciesDeficiencies
Cri-du-chat Cri-du-chat SyndromeSyndrome
A chromosomal duplication is usually caused by A chromosomal duplication is usually caused by abnormal events during recombinationabnormal events during recombination
DuplicationsDuplications
Phenotypic consequences of duplications Phenotypic consequences of duplications correlated to size & genes involvedcorrelated to size & genes involved
Duplications tend to be less detrimentalDuplications tend to be less detrimental
DuplicationsDuplications
Bar-Eye Phenotype in Bar-Eye Phenotype in DrosophilaDrosophila
Ultra-bar (or double-bar) is a trait in which flies have even Ultra-bar (or double-bar) is a trait in which flies have even fewer facets than the fewer facets than the barbar homozygote homozygote
Trait is X-linked and show intermediate dominanceTrait is X-linked and show intermediate dominance
Bar-eye Phenotype due to DuplicationBar-eye Phenotype due to Duplication
A segment of chromosome that is flipped relative to A segment of chromosome that is flipped relative to that in the homologuethat in the homologue
InversionsInversions
Centromere lies within inverted
region
Centromere lies outside inverted
region
InversionsInversions
No loss of genetic informationNo loss of genetic information Many inversions have no phenotypic consequencesMany inversions have no phenotypic consequences
Break point effectBreak point effect Inversion break point is within regulatory or structural portion of a Inversion break point is within regulatory or structural portion of a
genegene
Position effectPosition effect Gene is repositioned in a way that alters its gene expressionGene is repositioned in a way that alters its gene expression separated from regulatory sequences, placed next to constitutive separated from regulatory sequences, placed next to constitutive
heterochromatinheterochromatin
~ 2% of the human population carries karyotypically ~ 2% of the human population carries karyotypically detectable inversionsdetectable inversions
Individuals with one copy of a normal chromosome and one Individuals with one copy of a normal chromosome and one
copy of an inverted chromosomecopy of an inverted chromosome Usually phenotypically normalUsually phenotypically normal
Have a high probability of producing gametes that are abnormal in Have a high probability of producing gametes that are abnormal in genetic contentgenetic content
Abnormality due to crossing-over within the inversion intervalAbnormality due to crossing-over within the inversion interval
During meiosis I, homologous chromosomes synapse with During meiosis I, homologous chromosomes synapse with each othereach other For the normal and inversion chromosome to synapse properly, an For the normal and inversion chromosome to synapse properly, an
inversion loopinversion loop must form must form If a cross-over occurs within the inversion loop, highly abnormal If a cross-over occurs within the inversion loop, highly abnormal
chromosomes are producedchromosomes are produced
Inversion HeterozygotesInversion Heterozygotes
Crossing Over Within Inversion Interval Crossing Over Within Inversion Interval Generates Unequal Sets of ChromatidsGenerates Unequal Sets of Chromatids
Crossing Over Within Inversion Interval Crossing Over Within Inversion Interval Generates Unequal Sets of ChromatidsGenerates Unequal Sets of Chromatids
Inversions Prevent Generation of Inversions Prevent Generation of Recombinant Offspring GenotypesRecombinant Offspring Genotypes Only parental chromosomes (non-Only parental chromosomes (non-
recombinants) will produce normal recombinants) will produce normal progeny after fertilizationprogeny after fertilization
When a segment of one chromosome becomes When a segment of one chromosome becomes attached to another attached to another
InIn reciprocal translocationsreciprocal translocations two non-homologous two non-homologous chromosomes exchange genetic material chromosomes exchange genetic material Usually generate so-called Usually generate so-called balanced translocationsbalanced translocations
Usually without phenotypic consequencesUsually without phenotypic consequences Although can result in position effectAlthough can result in position effect
TranslocationsTranslocations
Fig. 8.13b(TE Art)Fig. 8.13b(TE Art)Nonhomologous chromosomes
Reciprocaltranslocation
1 1 7 7
Nonhomologous crossover
1 7
Crossover betweennonhomologouschromosomes
Fig. 8.13a(TE Art)Fig. 8.13a(TE Art)22
Environmental agent causes 2 chromosomes to break.
Reactive ends
22
2 2
DNA repair enzymesrecognize broken ends and connect them.
Chromosomal breakage and DNA repair
InIn simple translocationssimple translocations the transfer of genetic the transfer of genetic material occurs in only one directionmaterial occurs in only one direction These are also called These are also called unbalanced translocationsunbalanced translocations
Unbalanced translocations are associated with Unbalanced translocations are associated with phenotypic abnormalities or even lethalityphenotypic abnormalities or even lethality
Example: Familial Down SyndromeExample: Familial Down Syndrome In this condition, the majority of chromosome 21 is In this condition, the majority of chromosome 21 is
attached to chromosome 14attached to chromosome 14
Individuals carrying balanced translocations have a Individuals carrying balanced translocations have a greater risk of producing gametes with unbalanced greater risk of producing gametes with unbalanced combinations of chromosomescombinations of chromosomes This depends on the segregation pattern during meiosis IThis depends on the segregation pattern during meiosis I
During meiosis I, homologous chromosomes During meiosis I, homologous chromosomes synapse with each othersynapse with each other For the translocated chromosome to synapse properly, a For the translocated chromosome to synapse properly, a
translocation crosstranslocation cross must form must form
Balanced Translocations and Balanced Translocations and Gamete ProductionGamete Production
Meiotic segregation can occur in one of three waysMeiotic segregation can occur in one of three ways 1. Alternate segregation1. Alternate segregation
Chromosomes on opposite sides of the translocation cross Chromosomes on opposite sides of the translocation cross segregate into the same cellsegregate into the same cell
Leads to balanced gametesLeads to balanced gametes Both contain a complete set of genes and are thus viableBoth contain a complete set of genes and are thus viable
2. Adjacent-1 segregation2. Adjacent-1 segregation Adjacent non-homologous chromosomes segregate into the Adjacent non-homologous chromosomes segregate into the
same cellsame cell Leads to unbalanced gametesLeads to unbalanced gametes
Both have duplications and deletions and are thus inviableBoth have duplications and deletions and are thus inviable
3. Adjacent-2 segregation3. Adjacent-2 segregation Adjacent homologous chromosomes segregate into the same Adjacent homologous chromosomes segregate into the same
cellcell Leads to unbalanced gametesLeads to unbalanced gametes
Both have duplications and deletions and are thus inviableBoth have duplications and deletions and are thus inviable