Chromosome Structure and Function Quiz

DNA: The Genetic Material

• DNA is the genetic material of eukaryotes
• A single set of human chromosomes, when stretched end-to-end, would be over 1 meter long
• The cell's nucleus is only 2 to 4 mm in diameter
• DNA must be tightly compacted to fit within the nucleus

Structure of Eukaryotic Chromosomes in Nondividing Cells

• Chromatin is a DNA-protein complex
• Chromatin is composed of nucleosomes, the 30-nm fiber, and radial loop domains
• Nucleosomes support the beads-on-a-string model
• Noll's results support the beads-on-a-string model
• A chromosome territory is a distinct region for each chromosome in the nucleus
• Euchromatin and heterochromatin differ in their degree of condensation
• Constitutive heterochromatin and facultative heterochromatin also differ in their degree of condensation

Eukaryotic Chromatin Compaction

• DNA must be tightly packaged within the nucleus
• Interactions between DNA and proteins facilitate compaction
• In eukaryotes, this DNA-protein complex is known as chromatin
• Changes in proteins affect chromatin compaction during the cell cycle

Nucleosomes

• The nucleosome is the repeating structural unit of eukaryotic chromatin
• A nucleosome is double-stranded DNA wrapped around an octamer of histone proteins.
• The octamer is composed of two copies each of four different histones (H2A, H2B, H3, and H4)
• 146 or 147 base pairs of DNA make 1.65 negative superhelical turns around the octamer
• The linker region between nucleosomes is 20 to 100 base pairs

Histone Proteins

• Histone proteins contain positively-charged amino acids (lysine and arginine)
• These amino acids bind to the negatively charged phosphates in the DNA
• Histone proteins have a globular domain and a flexible charged amino terminus (tail)
• There are five types of histones: H2A, H2B, H3, H4 (core histones), and H1 (linker histone)

The Structure of the Nucleosome

• Roger Kornberg proposed a model of nucleosome structure in 1974.
• DNA double helix wraps around an octamer of core histone proteins
• Kornberg based this proposal on biochemical experiments, X-ray diffraction studies, and electron microsocopy images

The Structure of the Nucleosome2

• Markus Noll tested Kornberg's model
• If Kornberg's model is correct, Digesting the linker region of chromatin should result in DNA fragments that are only 200 base pairs long
• Linker DNA is more accessible than core DNA to the enzyme DNase I
• DNase I cuts should occur in the linker DNA but not the DNA wrapped around the core histones

Nucleosomes Join to Form a 30-nm Fiber

• Nucleosomes associate with each other to form a more compact 30-nm fiber
• This structure shortens the total length of DNA 7-fold
• The zigzag model for the structure of the 30-nm fiber is currently a model
• The structure is complex and has been difficult to determine

Further Compaction of the Chromosome

• Nucleosomes and the 30-nm fiber shorten the DNA about 50-fold.
• A third level of compaction involves formation of loops (called loop domains)
• CCCTC binding factor (CTCF) binds to three regularly spaced repeats of the sequence CCCTC
• Two different CTCFs bind to the DNA to form a loop
• SMC proteins can also form a loop
• SMC proteins are often found in the region of CTCFs

Chromosome Territories

• Each chromosome in the nucleus is located in a distinct chromosome territory
• These are visible when chromosomes are fluorescently labeled in interphase cells

Heterochromatin versus Euchromatin

• Euchromatin is less condensed and transcriptionally active
• Heterochromatin is tightly compacted and transcriptionally inactive

Constitutive versus Facultative Heterochromatin

• Constitutive heterochromatin is present in all cell types and contains highly repetitive sequences
• Examples include centromeres and telomeres
• Facultative heterochromatin differs among different cells of the body
• It occurs where genes are located
• It can convert to euchromatin as a way to regulate gene expression

Structure of Eukaryotic Chromosomes During Cell Division

• The levels of compaction lead to a metaphase chromosome
• As cells enter M phase, the level of compaction dramatically changes.

Metaphase Chromosomes

• Nucleosomes form a zigzag structure to form a 30-nm fiber
• 30-nm fibers form loop domains.
• Closer association of loop domains with each other and between adjacent nucleosomes.
• The diameter of a metaphase chromosome is 700 nm; two chromatids have a diameter of 1400 nm.
• Metaphase chromosomes are very compact, which may result in little gene transcription.

Metaphase Chromosomes2

• Controversy over whether or not nonhistone proteins form a scaffold for organizing the shape of metaphase chromosomes
• When a metaphase chromosome is treated with high salt to remove the histones the highly compact configuration is lost
• Bottoms of loops remain attached to a scaffold made of nonhistone proteins.

Deletions

• The phenotypic consequences of deletions depend on the size of the deletion and the chromosomal material that is deleted, and whether or not the lost genes are vital to the survival of the organism
• A chromosomal deletion occurs when a chromosome breaks and a fragment is lost.
• A deletion may be terminal or interstitial.
• Deletions can result in harmful effects, such as Cri-du-chat syndrome in humans

Duplications

• Duplications result in extra genetic material
• Duplications may be caused by abnormal crossing over
• Nonallelic homologous recombination may occur where the sites of duplication are similar but not exactly the same.
• Duplications tend to have milder effects compared to deletions

Inversions

• A chromosomal inversion is a segment that has been flipped to the opposite orientation
• Pericentric inversions contain the centromere within the inverted region
• Paracentric inversions contain the centromere outside the inverted region
• In rare cases, inversions can alter the phenotype of an individual
• The breaks leading to the inversion may occur in a vital gene

Inversion Heterozygotes

• Individuals with one normal chromosome and one inverted chromosome may be phenotypically normal
• However, they have a high probability of producing abnormal gametes due to crossing over in the inverted segment
• Nondisjunction may result in unequal segregation of homologous chromosomes in meiosis, which can cause a dicentric chromosome or an acentric fragment.

Translocations

• A chromosomal translocation occurs when a segment of one chromosome becomes attached to another
• Broken chromosome ends lack telomeres and become reactive
• In reciprocal translocations, two non-homologous chromosomes exchange genetic material

Reciprocal Translocations

• Reciprocal translocations lead to a rearrangement of the genetic material
• They are usually without phenotypic consequences, but in a few cases may result in position effects due to changes in gene expression

Unbalanced Translocations

• Carriers of balanced translocations are at risk of having offspring with unbalanced translocations
• In unbalanced translocations, significant portions of genetic material are duplicated and or deleted.

Robertsonian Translocation

• Most common type of chromosome rearrangement in humans
• The majority of chromosome 21 is attached to chromosome 14
• This translocation occurs such that the breaks occur at the extreme ends of two non-homologous chromosomes
• The small acentric fragments are lost; larger fragments fuse at centromeric regions to form a single chromosome

Changes in Chromosome Number: An Overview

• Polyploidy and Aneuploidy are two main variations of chromosome number
• Euploidy is the variation in the number of complete sets of chromosomes
• Aneuploidy is the variation in particular chromosomes within a set
• Examples of euploidy include triploid (3n), tetraploid (4n) and polyploid
• Examples of aneuploidy include trisomy (2n +1), monosomy (2n-1)

Aneuploidy in humans

• Autosomal aneuploidies most compatible with survival are trisomies 13, 18, and 21
• Sex chromosome aneuploidies generally have less severe effects due to X inactivation
• All but one X chromosome is transcriptionally suppressed
• Phenotypes of X chromosome aneuploidies may be due to expression of X-linked genes prior to X-inactivation

Influence of Age on Aneuploidies

• Some human aneuploidies are influenced by parental age
• Older parents are more likely to produce abnormal offspring, particularly in Down syndrome (Trisomy 21)
• Nondisjunction, usually in meiosis I in the oocyte, may contribute to aneuploidy
• Primary oocytes are produced in the ovary of a fetus before birth, are arrested in prophase I, and remain arrested until ovulation

Euploidy

• Most species of animals are diploid organisms
• Polyploidy in mammals is generally a lethal condition

Euploidy 2

• Some euploidy variations are naturally occurring, like with bees, which are haplodiploid
• Female bees are diploid, and male bees are monoploid (contain a single set of chromosomes)
• Many examples of vertebrate polyploid animals have been discovered, such as the frog Hyla

Endopolyploidy

• Diploid animals sometimes produce tissues that are polyploid, which is termed endopolyploidy
• Liver cells of diploid animals can be triploid, tetraploid, or even octoploid
• The polytene chromosomes of insects provide an unusual example of natural variation in ploidy

Polytene Chromosomes

• Polytene chromosomes occur mainly in the salivary glands of Drosophila and a few other insects
• Polytene chromosomes have facilitated the study of the organization and functioning of interphase chromosomes
• Polytene chromosomes are easily seen under a microscope even in interphase
• Each polytene chromosome has a characteristic banding pattern
• During interphase the chromosomes undergo repeated rounds of chromosome replication without cellular division in the salivary glands in Drosophila and some other insects to eventually become a bundle termed a polytene chromosome

Polyploidy

• Polyploidy is a condition where cells of an organism have more than two paired sets of chromosomes
• Polyploidy is common in plants, particularly among 30 to 35% of ferns and flowering plants
• Polyploid strains are often larger in size and more robust, and many fruits and grains are polyploids

Polyploids

• Polyploids with an odd number of chromosome sets are usually sterile, as they cannot normally produce functional gametes
• This may be due to unequal separation of homologous chromosomes during anaphase I in this triploid organism

Sterility in Agriculture

• Sterility is generally a detrimental trait, but in some agricultural applications can be desirable
• Triploid varieties of certain fruits (watermelon, bananas) and flowers (marigolds) are sterile and thus seedless - often desirable characteristics in agriculture
• Seedless plants are commonly propagated by cuttings

Mechanisms That Produce Variation in Chromosome Number

• Meiosis and mitosis nondisjunction
• Autoploidy
• Alloploidy
• Allopolyploidy
• Colchicine promotes polyploidy

Chromosome Number Variation

• Meiotic nondisjunction
• Mitotic nondisjunction
• Alloploidy (interspecies crosses)

Meiotic Nondisjunction

• Nondisjunction is the failure of chromosomes to segregate properly during anaphase (either meiosis I or II)
• Meiotic nondisjunction can produce cells with too many or too few chromosomes
• If a gamete with an abnormal chromosome number is involved in fertilization, the zygote will have an abnormal number of chromosomes

Complete Nondisjunction

• In rare cases, all chromosomes can undergo nondisjunction, resulting in one diploid daughter cell and one without chromosomes
• The chromosome-less cell is nonviable, but the diploid cell can participate in fertilization with a normal gamete, producing a triploid individual

Mitotic Nondisjunction

• Mitotic nondisjunction occurs after fertilization when sister chromatids separate improperly in daughter cells
• It results in one cell having complete sets of chromosomes (normal) and one daughter cell with incomplete sets (monosomic)
• Chromosome loss can happen where one sister chromatid does not migrate to a pole in the daughter cell

Autopolyploidy

• Autopolyploidy results from changes in the number of complete chromosome sets within an organism
• Can be produced through complete nondisjunction, resulting in an individual having 1 or more extra chromosome sets.

Allopolyploidy

• Allopolyploidy is a type of polyploidy that occurs when a polyploid offspring is generated from two distinct parental species.
• These offspring usually contain complete chromosome sets from both parent species.

Experimental Treatments Can Promote Polyploidy

• Polyploid and allopolyploid plants often exhibit desirable traits, so inducing these conditions in plants can be advantageous in agriculture
• Abrupt changes in temperature or the drug colchicine may induce polyploidy.
• Colchicine binds to tubulin, and interferes with proper chromosome segregation, potentially promoting nondisjunction

Chromosome Classification

• Chromosomes can be classified based on size, position of the centromere, and banding patterns
• Metacentric, submetacentric, acrocentric, and telocentric chromosomes differ by centromere location