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