Chapter 14Chapter 14

Chromosomal Rearrangements Chromosomal Rearrangements and Changes in Chromosome and Changes in Chromosome Number Reshape Eukaryotic Number Reshape Eukaryotic

GenomesGenomes

Outline of Chapter 14Outline of Chapter 14 Rearrangements of DNA sequences within and Rearrangements of DNA sequences within and

between chromosomesbetween chromosomes DeletionsDeletions DuplicationsDuplications InversionsInversions TranslocationsTranslocations Movements of transposable elementsMovements of transposable elements

Changes in chromosome numberChanges in chromosome number Aneuploidy: monosomy and trisomyAneuploidy: monosomy and trisomy MonoploidyMonoploidy PolyploidyPolyploidy

Deletions Deletions remove remove genetic genetic

material material from from

genomegenome

Fig. 13.2

Phenotypic consequences of Phenotypic consequences of heterozygosityheterozygosity

Homozygosity Homozygosity for deletion is for deletion is often but not often but not always lethalalways lethal

Heterozygosity Heterozygosity for deletion is for deletion is often often detrimentaldetrimental

Fig. 13.3

Deletion heterozygotes affect Deletion heterozygotes affect mapping distancesmapping distances

Recombination between homologues can only occur if both Recombination between homologues can only occur if both carry copies of the genecarry copies of the gene

Deletion loop formed if heterozygous for deletionDeletion loop formed if heterozygous for deletion Identification of deletion location on chromosomeIdentification of deletion location on chromosome

Genes within can not be separated by recombinationGenes within can not be separated by recombination

Fig. 13.4 a

Deletion loops in polytene Deletion loops in polytene chromosomeschromosomes

Fig. 13.4 b

Deletions in heterozygotes can Deletions in heterozygotes can uncover genesuncover genes

Pseudodominance shows a deletion has Pseudodominance shows a deletion has removed a particular generemoved a particular gene

Fig. 13.5

Deletions can be used to locate genesDeletions can be used to locate genes Deletions to Deletions to

assign genes to assign genes to bands on bands on Drosophila Drosophila polytene polytene chromosomeschromosomes

Complementation Complementation tests crossing tests crossing deletion mutants deletion mutants with mutant with mutant genes of genes of interestsinterests

Deletion Deletion heterozygote heterozygote reveals reveals chromosomal chromosomal location of location of mutant genemutant geneFig. 13.6

Deletions to locate genes at the Deletions to locate genes at the molecular levelmolecular level

Labeled probe hybridizes to wild-type Labeled probe hybridizes to wild-type chromosome but not to deletion chromosome but not to deletion chromosomechromosome

Fig. 13.7 a

Molecular mapping of deletion Molecular mapping of deletion breakpoints by Southern blottingbreakpoints by Southern blotting

Fig. 13.7 b, c

Duplications add material to the Duplications add material to the genomegenome

Fig. 13.8 a,b

Duplication loops form when chromosomes pair in Duplication loops form when chromosomes pair in duplication heterozygotesduplication heterozygotes

In prophase I, the duplication loop can In prophase I, the duplication loop can assume different configurations that assume different configurations that maximize the pairing of related regionsmaximize the pairing of related regions

Fig. 13.8 c

Duplications can affect phenotypeDuplications can affect phenotype

Novel phenotypesNovel phenotypes More gene copiesMore gene copies Genes next to Genes next to

duplication duplication displaced to new displaced to new environment environment altering expressionaltering expression

Fig. 13.9

Unequal crossing over between duplications Unequal crossing over between duplications increases or decreases gene copy numberincreases or decreases gene copy number

Fig. 13.10

Fig. 13.10Fig. 13.10

Summary of duplication and Summary of duplication and deletion effects on phenotpyedeletion effects on phenotpye

Alter number of genes on a chromosome and may Alter number of genes on a chromosome and may affect phenotype of heterozygoteaffect phenotype of heterozygote

Heterozygosity create one or three gene copies and Heterozygosity create one or three gene copies and create imbalance in gene product altering create imbalance in gene product altering phenotypes (some lethal)phenotypes (some lethal)

Genes may be placed in new location that modifies Genes may be placed in new location that modifies its expressionits expression

Deletions and duplications drive evolution by Deletions and duplications drive evolution by generating families of tandemly repeated genesgenerating families of tandemly repeated genes

Inversions reorganize the DNA Inversions reorganize the DNA sequence of a chromosomesequence of a chromosome

Produced by half Produced by half rotation of rotation of chromosomal regions chromosomal regions after double-stranded after double-stranded breakbreak

Also rare crossover Also rare crossover between related genes between related genes in opposite orientation in opposite orientation or transpositionor transposition

Fig. 13.11a,b

An inversion can affect phenotype if An inversion can affect phenotype if it disrupts a geneit disrupts a gene

Fig. 13.11 c

Inversion heterozygotes reduce the Inversion heterozygotes reduce the number of recombinant progenynumber of recombinant progeny

Inversion loop in Inversion loop in heterozygote forms heterozygote forms tightest possible tightest possible alignment of alignment of homologous regionshomologous regions

Fig. 13.12

Gametes produced from pericentric and Gametes produced from pericentric and paracentric inversions are imbalancedparacentric inversions are imbalanced

Fig. 13.13

Pericentric inversion Paracentric inversion (cont’d) (cont’d)

Fig. 13.13 cont’d

Inversions suppress recombinationInversions suppress recombination

Balancer chromosomes carry both a Balancer chromosomes carry both a dominant marker D and inversions dominant marker D and inversions (brackets) that prevent recombination with (brackets) that prevent recombination with experimental chromosome. experimental chromosome.

Heterozygous parent will transmit balancer Heterozygous parent will transmit balancer or experimental chromosome.or experimental chromosome.

Dominant mutation has an easily Dominant mutation has an easily distinguished phenotpye (e.g., curly wing)distinguished phenotpye (e.g., curly wing)

Translocations attach on part of a Translocations attach on part of a chromosome to anotherchromosome to another

Translocation – part of one chromosome Translocation – part of one chromosome becomes attached to nonhomologous becomes attached to nonhomologous chromosomechromosome

Reciprocal translocation – two different parts of Reciprocal translocation – two different parts of chromosomes switch placeschromosomes switch places Fig. 13.15 a

Robertsonian translocations can Robertsonian translocations can reshape genomesreshape genomes

Reciprocal exchange between acrocentric Reciprocal exchange between acrocentric chromosomes generate large metacentric chromosomes generate large metacentric chromosome and small chromosomechromosome and small chromosome Tiny chromosome may be lost from organismTiny chromosome may be lost from organism

Fig. 13.16

Leukemia patients have too many blood cells

Fig. 13.17

Heterozygosity for translocations diminishes Heterozygosity for translocations diminishes fertility and results in pseudolinkagefertility and results in pseudolinkage

Fig. 13.18 a.b

Three possible segregation patterns in a translocation Three possible segregation patterns in a translocation heterozygote from the cruciform configurationheterozygote from the cruciform configuration

Pseudolinkage – because only alternate segregation patterns produce viable progeny, genes near

breakpoints act as if linked

Fig. 13.18 c

Semisterility Semisterility results from results from translocation translocation heterozygotesheterozygotes < 50% of gametes < 50% of gametes

arise from arise from alternate alternate segregation and segregation and are viableare viable

Fig. 13.18 d

Translocation Down syndromeTranslocation Down syndrometranslocation of chromosome 21 is small and thus produces translocation of chromosome 21 is small and thus produces

viable gamete, but with phenotypic consequenceviable gamete, but with phenotypic consequence

Fig. 13.19

Transposable elements move from Transposable elements move from place to place in the genomeplace to place in the genome

1930s Marcus Rhoades and 1950s Barbara McClintock – 1930s Marcus Rhoades and 1950s Barbara McClintock – transposable elements in corntransposable elements in corn

1983 McClintock received Nobel Prize1983 McClintock received Nobel Prize Found in all organismsFound in all organisms Any segment of DNA that evolves ability to move from one Any segment of DNA that evolves ability to move from one

place to another in genomeplace to another in genome Selfish DNA carrying only information to self-perpetuateSelfish DNA carrying only information to self-perpetuate Most 50 – 10,000 bpMost 50 – 10,000 bp May be present hundreds of time in a genomeMay be present hundreds of time in a genome LINES, long interspersed element in mammalsLINES, long interspersed element in mammals

~ 20,000 copies in human genome up to 6.4kb in length~ 20,000 copies in human genome up to 6.4kb in length SINES, short interspersed elements in mammalsSINES, short interspersed elements in mammals

~ 300,000 copies in human genome~ 300,000 copies in human genome ~ 7% of genome are LINES and SINES~ 7% of genome are LINES and SINES

Retroposons generate an RNA that encodes a Retroposons generate an RNA that encodes a reverse transciptase like enzymereverse transciptase like enzyme

Two typesTwo types Poly-A tail at 3’ Poly-A tail at 3’

end of RNA-like end of RNA-like DNA strandDNA strand

Long terminal Long terminal repeat (LTRs) repeat (LTRs) oriented in same oriented in same direction on either direction on either end of elementend of element

Fig. 13.23 a

Fig. 13.23 b

The process of LTR transpositionThe process of LTR transposition

Fig. 13.23

Transposons encode transposase enzymes that Transposons encode transposase enzymes that catalyze events of transpositioncatalyze events of transposition

Fig. 13.24 a

P elements in DrosophilaP elements in Drosophila After excision of P element transposon, DNA After excision of P element transposon, DNA

exonucleases first widen gap and then repair itexonucleases first widen gap and then repair it Repair uses sister chromatid or homologous Repair uses sister chromatid or homologous

chromosome as a templatechromosome as a template P strains of Drosophila have many copies of P P strains of Drosophila have many copies of P

elementselements M strains have no copiesM strains have no copies Hybrid dysgenesis – defects including sterility, Hybrid dysgenesis – defects including sterility,

mutation, and chromosomal breakage from cross mutation, and chromosomal breakage from cross between P and M strainsbetween P and M strains Promotes movement of P elements to new positionsPromotes movement of P elements to new positions

Genomes often contain defective Genomes often contain defective copies of transposable elementscopies of transposable elements

Many TEs sustain deletions during Many TEs sustain deletions during transposition or repairtransposition or repair

If promoter needed for transcription If promoter needed for transcription deleted, TE can not transpose againdeleted, TE can not transpose again

Most SINES and LINES in human genome Most SINES and LINES in human genome are defective TEsare defective TEs

Nonautonomous elements – need activity of Nonautonomous elements – need activity of nondeleted copies of same TE for movementnondeleted copies of same TE for movement

Autonomous elements – move by themselvesAutonomous elements – move by themselves

TEs can generate mutations in adjacent genesTEs can generate mutations in adjacent genesspontaneous mutations in white gene of Drosophilaspontaneous mutations in white gene of Drosophila

Fig. 13.25

TEs can generate chromosomal rearrangements and TEs can generate chromosomal rearrangements and relocate genesrelocate genes

Fig. 13.26

The loss or gain of one or more The loss or gain of one or more chromosomes results in aneuploidychromosomes results in aneuploidy

Autosomal aneuploidy is harmful to the organismAutosomal aneuploidy is harmful to the organism

Monosomy usually lethalMonosomy usually lethal Trisomies – highly deleteriousTrisomies – highly deleterious

Trisomy 18 – Edwards syndromeTrisomy 18 – Edwards syndrome Trisomy 13 – Patau syndromeTrisomy 13 – Patau syndrome Trisomy 21 – Down syndromeTrisomy 21 – Down syndrome

Humans tolerate X chromosome aneuploidy Humans tolerate X chromosome aneuploidy because X inactivation compensates for dosagebecause X inactivation compensates for dosage

Fig. 13.27

Mitotic nondisjunctionMitotic nondisjunction Failure of two sister chromatids to separate during mitotic Failure of two sister chromatids to separate during mitotic

anaphaseanaphase Generates reciprocal trisomic and monosomic daughter cellsGenerates reciprocal trisomic and monosomic daughter cells

Chromosome lossChromosome loss Produces one monosomic and one diploid daughter cellProduces one monosomic and one diploid daughter cell

Fig. 13.28 a

Mosaics – aneuploid and normal tissues that lie Mosaics – aneuploid and normal tissues that lie side-by-sideside-by-side Aneuploids give rise to aneuploid clonesAneuploids give rise to aneuploid clones

Fig. 13.28 b

Gynandromorph in Drosophila results from female Gynandromorph in Drosophila results from female losing one X chromosome during first mitotic losing one X chromosome during first mitotic

division after fertilizationdivision after fertilization

Fig. 13.29

Euploid individuals contain only Euploid individuals contain only complete sets of chromosomescomplete sets of chromosomes

Monoploid organisms contain a single copy of Monoploid organisms contain a single copy of each chromosome and are usually infertileeach chromosome and are usually infertile

Monoploid plants have many usesMonoploid plants have many uses Visualize recessive traits directlyVisualize recessive traits directly Introduction of mutations into individual cellsIntroduction of mutations into individual cells Select for desirable phenotpyes (herbicide Select for desirable phenotpyes (herbicide

resistance)resistance) Hormone treatment to grow selected cellsHormone treatment to grow selected cells

Fig. 13.30

Treatment with colchicine converts back to diploidTreatment with colchicine converts back to diploid

plants that express desired phenotypesplants that express desired phenotypes

Fig. 13.30 c

Polyploidy has accompanied the Polyploidy has accompanied the evolution of many cultivated plantsevolution of many cultivated plants

1:3 of flowering plants are polyploid1:3 of flowering plants are polyploid Polyploid often increases size and vigorPolyploid often increases size and vigor Often selected for agricultural cultivationOften selected for agricultural cultivation

Tetraploids - alfalfa, coffee, peanutsTetraploids - alfalfa, coffee, peanuts Octaploid - strawberriesOctaploid - strawberries

Fig. 13.31

Triploids are Triploids are almost always almost always sterilesterile

Result from union Result from union of monoploid and of monoploid and diploid gametesdiploid gametes

Meiosis produces Meiosis produces unbalanced unbalanced gametesgametes

Fig. 13.32

Tetraploids are often source of new speciesTetraploids are often source of new species Failure of chromosomes to separate into two Failure of chromosomes to separate into two

daughter cells during mitosis in diploiddaughter cells during mitosis in diploid Cross between tetraploid and diploid creates Cross between tetraploid and diploid creates

triploids – new species, autopolyploidstriploids – new species, autopolyploids

13.33 a

Maintenance of Maintenance of tetraploid species tetraploid species depends on the depends on the production of gametes production of gametes with balanced sets of with balanced sets of chromosomeschromosomes

Bivalents- pairs of Bivalents- pairs of synapsed homologous synapsed homologous chromosomes that chromosomes that ensure balanced ensure balanced gametesgametes

Fig. 13.33 b

Fig. 13.33 c

Some polyploids have agriculturally desirable traits Some polyploids have agriculturally desirable traits derived from two speciesderived from two species

Amphidiploids created by Amphidiploids created by chromosome doubling in chromosome doubling in germ cellsgerm cells

e.g., wheat – cross e.g., wheat – cross between tetraploid wheat between tetraploid wheat and diploid rye produce and diploid rye produce hybrids with desirable hybrids with desirable traitstraits

Fig. 13.34