Chromosome Structure, Nucleosome Model Chromosome Structure, Nucleosome Model & Variation in chromosome number, Chromosome Alterations Dr. Madhumita Bhattacharjee Assiatant Professor Botany Deptt. P.G.G.C.G. -11,Chandigarh

Chromosomes and Genetics Basic review: Chromosomes are long pieces of DNA, with supporting proteins. Genes are short regions of this DNA that hold the information needed to build and maintain the body Genes have fixed locations: each gene is in a particular place on a particular chromosome Diploids have 2 copies of each chromosome, one from each parent. This means 2 copies of each gene. The interactions between the 2 copies of each gene give rise to the various forms of dominance.

Chromosomes The essential part of a chromosome is a single very long strand of DNA. This DNA contains all the genetic information for creating and running the organism. Each chromosome has a central constricted region called a centromere that serves as an attachment point for the machinery of mitosis.

Chromosomes Chromosomes exist in 2 different states, before and after they replicate their DNA. Before replication, chromosomes have one chromatid. After replication, chromosomes have 2 sister chromatids, held together at the centromere. Each chromatid is one piece of DNA with its supporting proteins. In mitosis, the two chromatids of each chromosome separate, with each chromatid going into a daughter cell.

Chromosomes = DNA

Eukaryotic chromosomal organization 2 main groups of proteins involved in folding/packaging eukaryotic chromosomes Histones = positively charged proteins filled with amino acids lysine and arginine that bond Nonhistones = less positive

Model for Chromatin Structure Chromatin is linked together every 200 bps (nuclease digestion) Chromatin arranged like “String onBeads” (electron microscope) 8 histones in each nucleosome 147 bps per nucleosome core particle with 53 bps for linker DNA (H1) Left-handed superhelix

Eukaryotic chromosomal organization Histone proteins Abundant Histone protein sequence is highly conserved among eukaryotes Provide the first level of packaging for the chromosome DNA is wound around histone proteins to produce nucleosomes; stretch of unwound DNA between each nucleosome

Eukaryotic chromosomal organization Nonhistone proteins Other proteins that are associated with the chromosomes Many different types in a cell; highly variable in cell types, organisms, and at different times in the same cell type Amount of nonhistone protein varies May have role in compaction or be involved in other functions requiring interaction with the DNA Many are acidic and negatively charged; bind to the histones; binding may be transient

Eukaryotic chromosomal organization Histone proteins 5 main types H1—attached to the nucleosome and involved in further compaction of the DNA (conversion of 10 nm chromatin to 30 nm chromatin) H2A H2B H3 H4 This structure produces 10nm chromatin Two copies in each nucleosome ‘histone octomer’; DNA wraps around this structure1.75 times

Nucleosome structure

10 nm chromatin is produced in the first level of packaging. Nucleosomes connected together by linker DNA and H1 histone to produce the “beads-on-a-string” extended form of chromatin 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 variation Allelic variations mutations in particular genes (loci) Chromosomal aberrations Changes in chromosome Number ( Numerical) Changes in chromosome Structure (Structural)

VARIATIONS IN CHROMOSOME Number

Variation In Chromosome Number Euploidy Normal variations of the number of complete sets of chromosomes Haploid, Diploid, Triploid, Tetraploid, etc… Aneuploidy Variation in the number of particular chromosomes within a set Monosomy, trisomy, polysomy

VARIATIONS IN CHROMOSOME STRUCTURE (CHROMOSOMAL REARRANGEMENTS) Deletions Loss of a region of a chromosome Duplications Inversions Pericentric – inversion about the centromere Paracentric – inversion not involving the centromere Translocations Exchange or joining of regions of two non-homologous chromosomes

Polyploidy v Aneuploidy

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Euploidy Variations Plants commonly exhibit polyploidy 30-35% of ferns and flowering plants are polyploid Many of the fruits & grain are polyploid plants Polyploid strains often display desirable agricultural characteristics wheat cotton strawberries bananas large blossom flowers

and two copies of other chromosomes one copy of some chromosomes Polyploidy Polyploids with odd chromosome sets are usually sterile produce mostly aneuploid gametes rare a diploid & haploid gamete are produced and two copies of other chromosomes Each cell receives one copy of some chromosomes

Benefit of Odd Ploidy-Induced Sterility Seedless fruit watermelons and bananas asexually propagated by human via cuttings Seedless flowers Marigold flowering plants Prevention of cross pollination of transgenic plants

Generation of Polyploids Autopolyploidy Complete nondisjunction of both gametes can produce an individual with one or more sets of chromosomes

Interspecies Crosses can Generate Alloploids Alloploidy Offspring generally sterile

Interspecies Crosses Result in Alloploids Allodiploid one set of chromosomes from two different species Allopolyploid combination of both autopolyploidy and alloploidy An allotetraploid: Contains two complete sets of chromosomes from two different species

Experimental Treatments Can Promote Polyploidy Polyploid and allopolyploid plants often exhibit desirable traits Colchicine is used to promote polyploidy Colchicine binds to tubulin, disrupting microtubule formation and blocks chromosome segregation

Variation In Chromosome Structure Amount of genetic information in the chromosome can change Deficiencies/Deletions Duplications The genetic material remains the same, but is rearranged Inversions Translocations

Deficiencies (Deletions) A chromosomal deficiency occurs when a chromosome breaks and a fragment is lost

Deficiencies Phenotypic consequences of deficiency depends on Size of the deletion Functions of the genes deleted Phenotypic effect of deletions usually detrimental

Cri-du-chat Syndrome

Duplications A chromosomal duplication is usually caused by abnormal events during recombination

Duplications Phenotypic consequences of duplications correlated to size & genes involved Duplications tend to be less detrimental

Bar-Eye Phenotype in Drosophila Ultra-bar (or double-bar) is a trait in which flies have even fewer facets than the bar homozygote Trait is X-linked and show intermediate dominance

Bar-eye Phenotype due to Duplication Figure: 07-12a Caption: (a) Genotypes & phenotypes.

Inversions A segment of chromosome that is flipped relative to that in the homologue Centromere lies within inverted region Centromere lies outside inverted region

Inversions No loss of genetic information Break point effect Many inversions have no phenotypic consequences Break point effect Inversion break point is within regulatory or structural portion of a gene Position effect Gene is repositioned in a way that alters its gene expression separated from regulatory sequences, placed next to constitutive heterochromatin ~ 2% of the human population carries karyotypically detectable inversions

Inversion Heterozygotes Individuals with one copy of a normal chromosome and one copy of an inverted chromosome Usually phenotypically normal Have a high probability of producing gametes that are abnormal in genetic content Abnormality due to crossing-over within the inversion interval During meiosis I, homologous chromosomes synapse with each other For the normal and inversion chromosome to synapse properly, an inversion loop must form If a cross-over occurs within the inversion loop, highly abnormal chromosomes are produced

Crossing Over Within Inversion Interval Generates Unequal Sets of Chromatids

Crossing Over Within Inversion Interval Generates Unequal Sets of Chromatids

Inversions Prevent Generation of Recombinant Offspring Genotypes Only parental chromosomes (non-recombinants) will produce normal progeny after fertilization

Translocations When a segment of one chromosome becomes attached to another In reciprocal translocations two non-homologous chromosomes exchange genetic material Usually generate so-called balanced translocations Usually without phenotypic consequences Although can result in position effect

Fig. 8.13b(TE Art) Nonhomologous chromosomes 1 1 7 7 Crossover between Reciprocal translocation Nonhomologous crossover

Fig. 8.13a(TE Art) 22 22 Environmental agent 2 2 causes 2 chromosomes to break. 2 2 Reactive ends DNA repair enzymes recognize broken ends and connect them. Chromosomal breakage and DNA repair

Example: Familial Down Syndrome In simple translocations the transfer of genetic material occurs in only one direction These are also called unbalanced translocations Unbalanced translocations are associated with phenotypic abnormalities or even lethality Example: Familial Down Syndrome In this condition, the majority of chromosome 21 is attached to chromosome 14

Balanced Translocations and Gamete Production Individuals carrying balanced translocations have a greater risk of producing gametes with unbalanced combinations of chromosomes This depends on the segregation pattern during meiosis I During meiosis I, homologous chromosomes synapse with each other For the translocated chromosome to synapse properly, a translocation cross must form

Meiotic segregation can occur in one of three ways 1. Alternate segregation Chromosomes on opposite sides of the translocation cross segregate into the same cell Leads to balanced gametes Both contain a complete set of genes and are thus viable 2. Adjacent-1 segregation Adjacent non-homologous chromosomes segregate into the same cell Leads to unbalanced gametes Both have duplications and deletions and are thus inviable 3. Adjacent-2 segregation Adjacent homologous chromosomes segregate into the same cell