CHROMOSOMES

OUTLINE
• Structural and functional organization of chromosomes
• Overview of Telomere structure and functions
• Ploidy
• Change in the Structure of Chromosomes
 Chromosomes
• Chromosomes– The 3 billion bases of the human genome are not all
in one continuous strand of DNA.
• The human genome is divided into 23 separate pairs of DNA, called
chromosomes.
• thread-like structures found INSIDE the nucleus of plants and animal cells.
Functionally regarded as linear collections of discrete transcriptional units,
each designed for the synthesis of a specific RNA molecule.
• Contains a continuous molecule of DNA which is wrapped around histones
• Human has 22 pairs of autosomes and 1 pair of sex chromosome
Chromosomes
 Genome
• Autosomes are non-sex determining chromosomes, while sex
chromosomes are X and Y chromosome.
• Male will have XY sex chromosomes, whereas female will carry XX sex
chromosomes
• The collection of chromosomes in an individual is called karyotype.
• The typical male karyotype has 22 pairs of autosomes, one X and one
Y chromosome.
The sex chromosomes

“the most compelling little scrap of stuff in existence.”

 The sex chromosomes

Humans and fruit flies have the XY genetic system

Y chromosome
“single-issue” chromosome designed to determine sex

X chromosome – ‘controlling’
 The sex chromosomes
In any given species, cytogenetic pattern between
homologous chromosomes is similar
In most species however, sex chromosomes tend to
be heteromorphic (variations in shape, size and gene
content)
Gene clustering patterns are also different
 Y chromosome
‘hall of mirrors’ – full of
palindromes

50Mb size - ~50 genes

2 domains
Pseudoautosomal region
(PAR) – 5%
Non-recombining
regions (NRY) – 95%

HMG3 pages 367-372

Genetic system
 Active genes on the human Y chromosome
Yellow bar, euchromatic NRY (non-
recombining region);
black bar, heterochromatic portion of
NRY;
red bars, pseudoautosomal regions
Genes to right: active X-chromosome
homologues.
Genes to left: lack known X homologues.
Genes in red: widely expressed
housekeeping genes;
genes in black: expressed only in testis
genes in green are expressed neither
widely, nor testis specifically
AMELY (amelogenin Y) is expressed in
developing tooth buds,
PCDHY (protocadherin Y) is expressed in
the brain)
Y chromosome shows the accumulation of spermatogenesis genes
and an overall functional decay typical of male-specific
chromosomes.
active genes on NRY region classed into 3 types on the basis of
tissue expression and homology to the X
Class 1: housekeeping genes with ancient homology to X
Class 2: testis-specific genes.
Class 3: genes variously similar to both classes 1 and 2, as well as
other genes that might be decaying towards pseudogene status, or the
persistence of which might reflect additional evolutionary factors at
work on the Y chromosome.

Genes that belong to classes 1 and 2 seem to underlie the medical

disorders Turner syndrome and male infertility, respectively.
Human sex-chromosome evolution

• Shrinkage of the Y chromosome

• Blockwise expansion of NRY (red regions)
• PCDX/Y translocated from x to the NRY (green regions)
 Chromosomes

• A term coined in the 1880s;

• Chromosome = “coloured bodies”
• It’s the carrier of genetic information.
• The cell nucleus contains the majority of the cell's genetic material, in
the form of multiple linear DNA molecules organized into structures
called chromosomes.
• During the S phase of the cell cycle, chromosomes duplicate to form
dyads
• The attached duplicate chromosomes are called sister chromatids.
Chromosomes
The problem
• Spacing between base pairs ≈3.4Å
• For human genome, approximately 3.2 billion
base pairs
• Total length ≈ 3.4×10-10×3.2×109×2 ≈ 2.2m
• Diameter of a nucleus: 5~10×10-6m
• Access to genetic information must be regulated.
Chromosome Organization in the Cell Cycle

• DNA are packaged with associated

proteins into chromosomes.

• Chromosomes undergo dramatic coiling

when cells divide. reorganization
Chromosome Related Nomenclature
• Chromatin: the complex of DNA, histones, and non-histone
proteins within the nucleus of a eukaryotic cell (DNA
persistence length ~50nm). The material of which
chromosomes are made.
• Chromatid: one of the two copies of a replicated
chromosome that is joined at the centromere to the other
copy. The two identical chromatids are called sister
chromatids.
• Centromere: the chromosomal region that holds sister
chromatids together and where the kinetochore forms.
• It is a constricted central portion of each chromosome
Centromere positions
Chromosome Related Nomenclature
• Kinetochore: the centromeric substructure
that binds microtubules and directs
chromosome movement in mitosis.

• Gene: a segment of DNA encoding

a functional RNA or protein product.
Chromosome Related Nomenclature
• Telomeres
• non-coding region at the ends of chromosomes.
• Short repeated sequence: about 500– 5000x

….TTAGGGTTAGGGTTAGGG….

• Includes specialized proteins

• forms a “capped” structure
• Sequence is conserved in all vertebrates, and similar in
most organisms
• Hence function must be important
• Importance of telomeres
• Protects the ends of chromosomes from nucleases
• Allows cells to distinguish chromosome ends from broken DNA
• Prevents chromosomes from fusing with each other
• Attachment to nuclear scaffold
PROBLEM
1. when chromosomes replicates in cells, the telomeres gets
progressively shorter.
2. End replication problem:
the shortening of DNA molecules with each cell division. Every
time a linear chromosome replicates, the lagging strand at each
end gets shorter by about 150 nucleotides.
DNA polymerase; an enzyme that replicates DNA strands.
Telomerase: is the solution
Telomerase is an RNA enzyme that
adds more nucleotides to the 3’
end of the telomere DNA strands.
• The steady loss of telomeres results in a limited life-span for most
cells
• In culture, most cells cycle for a number of times and die
• Same seem to happen in eukaryotic organisms due to lack of telomerase
enzyme in our cells
• Telomerase is not present in all cells
• Absent in cultured cells from normal tissue – divides 50x
• Present in tumor cells – unlimited divisions
• Present in one cell organisms – unlimited divisions
• Present in primordial gem cells – unlimited divisions
• Experimentally added to normal cells with telomerase genes – more cycles
observed
Could loss of telomeres cause the aging
process?
• Perhaps, but there are other factors too
Telomere shortening
Accumulated errors
Chronic risk exposures such as oxidants, UV
Glycation – sugar binding DNA, proteins, lipids

• loss of telomeres gives a maximal limit to the number of cell

divisions
• Could we provide telomerase therapy to restore telomere
length?
• Each round of replication leaves 50 – 200 bp unreplicated at the 3’ end
• Cells that have telomeres that are 10 – 12 kb in length (average) divides
50 – 60x

• Cellular Senescence; irreversible cell cycle arrest driven by a variety of

mechanisms, including telomere shortening, other forms of genotoxic

stress, or mitogens or inflammatory cytokines, that culminate in the

activation of the p53 tumor suppressor and/or the cyclin-dependent

kinase inhibitor.

• It is triggered when telomeres are about 4 – 6 kb long.

• Many cancer cells have reactivated their telomerase
• Some anticancer therapies are directed towards inhibiting
telomerase
• So if u think of extending life through telomerase therapy,
perhaps you may be at risk of cancer
 PLOIDY
• Ploidy indicates the number of sets of chromosomes
• Most animals are diploid – have two copies each of chromosome, one from the
mother and one from the father
• Gametes are haploid – have only one set – arise through meiosis
• Diploid number (2n) – number of chromosomes per somatic cell
• Haploid number (n) – number of chromosomes in gametes
• Human: 2n = 46
• Mouse: 2n = 40
• Drosophilia: 2n = 8
• The complete set of chromosome in the cells of an organism is its Karyotype.
• Human: 22 autosomes and 2 sex chromosomes
The number of chromosomes found in a single complete set of
chromosomes is called the monoploid number (x).
In most animals, the haploid number (n) is unique to gametes
(sperm or egg cells), and refers to the total number of
Chromosomes found in a gamete, which under normal conditions
is half the total number of chromosomes in a somatic cell.
 Ploidy
• Euploid: organism containing multiples of the basic chromosome set
• Monoploid: organisms with one chromosome set (in essentially
diploid taxa)
• Basic chromosome number, x (also called monoploid number): the
number of different chromosomes that make up a single complete
set. (In a diploid organism with 10 pairs of chromosomes, x = 10)
• Haploid number, n: number of chromosomes in the gametes (In
diploid organisms n=x, but this is not true for polyploid species.
Wheat is a hexaploid with 42 chromosomes; in this case x=7 and
n=21.)
• Allopolyploids: polyploids created by hybridization between different
species (homeologous chromosomes)
• Autopolyploids: polyploids created by chromosome duplication
within a species
 Ploidy
• Polyploid: organism containing more than two chromosome sets
• Polyploidy is much more common in plants.
• Roughly one of three known species of flowering plants are
polyploids.
• One-half of all known plant genera contain polyploid species and 2/3
of all grasses are polyploid.
• Examples are wheat (6x), alfalfa (4x), coffee (4x), peanuts (4x),
strawberries (8x), and cotton (4x).
• Ornamentals such as roses, chrysanthemums, and tulips are also
polyploid.
• Polyploidy is often associated with larger cells (because the nucleus is
larger), and polyploids tend to be larger and more robust.
 Ploidy
• There are a few examples of polyploidy in animals.
• It is rare probably because it interferes with sex-
determination.
• Usually, polyploid animals have unusual reproductive cycles.
E.g. Flatworms, leeches, brine shrimps, some salamander
and lizards, and goldfish are parthenogenetic.
• Triploid oysters have no sexual cycle (hence, no mating
season when oysters are usually unpalatable)
• Some polyploid amphibians (some frogs and toads) do use
sexual reproduction.
Aneuploidy: Abnormal number of chromosomes
• Aneuploid Individuals have a numerical change in part of the genome.
The chromosome number of aneuploids is not an exact multiple of
the haploid number, n.
• Hypoploid: an organism in which a chromosome (or part thereof)
is underrepresented.
• Hyperploid: an organism in which a chromosome (or part thereof)
is overrepresented
• Usually created by non-disjunction at meiosis I or II.
• If non-disjunction occurs at Meiosis I, none of the gametes
produced have the haploid number of chromosomes.
• If non-disjunction occurs at Meiosis II, then 2 normal gametes and
2 aneuploid gametes are produced.
Example of aneuploids in Humans
• Trisomies (2n + 1) do occur in humans and plants.
• The best known is Downs syndrome (trisomy of chromosome 21),
which occurs in approximately 1/700 live births.
• Other much rarer trisomies are Patau Syndrome (trisomy 13) and
Edwards Syndrome (trisomy 18).
• Individuals with trisomy 13 or 18 often die within the first few weeks
of birth.
Example of aneuploids in Humans
• All human monosomies (2n-1), are embryonic lethals.
• A few 21 monosomics have survived beyond birth with severe
multiple abnormalities.
• Turner Syndrome: (XO) female with retarded sexual development who
is usually sterile.
• the severity of the syndrome will depend upon when during
development the mitotic non-disjunction event occurred.
 Structural Change in the Structure of Chromosomes

• Chromosomes are the vehicle of hereditary material or

genes. Any alteration, addition or deletion of chromosomal
part leads to alteration of number, position or sequence of
genes in the chromosome.
• Such change of structure is referred to as chromosomal
aberrations or chromosomal mutations.
• Chromosomal aberrations involve two types of changes:
• Changes in number of genes in a chromosome
• Changes involving arrangement of genes.
• Changes in the number of genes in a chromosome:
I. Deletion or Deficiency: It is due to loss of a part of a
chromosome. The chromosome becomes shorter due to
loss of one or more genes
II. Duplication: may take place due to attachment of some
deleted part of another chromosome with it. This brings
addition of some new genes not belonging to it.
• Changes in the arrangement of genes in a chromosome:
I. Inversion: An inversion is produced when there are two
breaks in a chromosome and the intercalary segment re-
unites in reverse order i.e., the segment rotate by 180°. For
example, if the gene sequence in the original chromosome
is ABCDEFGH, it may change to ADCBEFGH
• If the inverted segment includes the centromere, the
inversion is called pericentric inversion; if it does not
include centromere the inversion is called as paracentric
inversion.

II. Translocation: Translocation involves transfer of a

segment of a chromosome to a different part of the same
chromosome or to a different chromosome.
• The chromosomal aberrations described above are the
outcome of defective meiotic division and result in changed
sequence of genes. The genes in new or changed location
may alter the phenotypic expression or may even cause
death of the individual.