LECTURE-3

PART- I CYTOGENETICS
 DUPLICATIONS

Occurs when a segment of a chromosome is duplicated.

 Chromosomal aberrations
Duplications -origin

Definition: Duplications occur, when a segment of the chromosome is

replicated.

Duplications arise:
1. In conjunction with deletions as we saw before.

2. Duplications arise due to DNA polymerase

replicating a loop twice or thrice, in error (before meiosis).

3. Higher order duplications occur due to unequal

crossing over (asymmetric crossing over) during meiosis.
Chromosomal aberrations
Duplications- origin

1. Duplications arise in conjunction with deletions.

Chromosomal aberrations
Duplications- origin
2. The DNA polymerase enzyme replicating a looped DNA
segment thrice.

DNA polymerase
e
f

d
g h
a b c

a b c d e f d e f d e f g h
Chromosomal aberrations
Duplications - origin
3. Higher order duplications are generated by asymmetric crossing
over (unequal crossing over).
Chromosomal aberrations
Duplications - origin
Unequal crossing over
Chromosomal aberrations
Duplications - types

 Adjacent duplication Tandem (abcdede - fghi)

Reverse tandem (abcdeed - fghi)

 Non-Adjacent Displaced homobrachial( adebcde - fghi)

Displaced heterobrachial (abcde – fdeghi)

Extra chromosome ( - de)

Adjacent types are more common and can lead to higher order
duplications through asymmetric crossing over.
Chromosomal aberrations
Duplications - Diagnosis
Diagnosis
Cytological detection:
Karyotype (mitotic metaphase)
 Duplicate banding pattern
 If duplication is large, increase in chromosome length

Meiotic chromosomes
 The bivalents show buckling, looping or coiling
Chromosomal aberrations
Duplications
Bivalents showing looping

BC
Chromosomal aberrations
Duplications – Evolutionary significance
Duplications serve as an evolutionary pump
1. Divergence of duplicated segments result in multigene families
When a duplication occurs, one of the segments is free to
undergo divergence to assume new functions, while the other
maintains the original function.
A multigene family is a family of genes derived from a single
ancestral gene by duplication followed by divergence.

Multigene families provide developmental flexibility,

environmental flexibility and opportunity for differentiation.
These capabilities confer to organism greater evolutionary
flexibility.
 Chromosomal aberrations
Duplications - Diagnosis
Normal female Bar mutation Bar mutation

Diagnosis
Genetic detection:
B+/B+ B/B+ B/B

Duplications are hard to detect genetically, since no function

is lost or gained (all genes are still there).

Occasionally novel phenotypes are produced

e.g. double bar mutation
Bar mutation produces small eyes, double bar results in slit like eyes.
Chromosomal aberrations
Duplications
Inheritance of duplications are normal

 There are no pairing problems during meiosis, as duplicated

segments are looped out in ‘duplication-heterozygotes’
Hence gametes are fully fertile and inheritance is normal.

 Non-tandem duplications can rarely undergo crossing over

within the looped segment to give some sterility.
Chromosomal aberrations
Duplications
Chromosomal aberrations
Duplications - Inheritance

Why do duplications accumulate in genomes?

 There are no genes lost (hence no loss in function). Natural

section does not eliminate duplicated sequences.

 Inheritance of duplications are normal

 Once duplications occur they lead to higher order

duplications (results in gene redundancy).
 Chromosomal aberrations
Duplications – hemoglobin molecule

2 α and 2
β chains
 Chromosomal aberrations e.g. hemoglobin gene family

Psi (Ψ) = pseudogene

 Chromosomal aberrations
e.g. Hemoglobin gene family
The hemoglobin gene family is an example of a dispersed gene family
It consists of:
β-cluster consisting of 5 functional genes ε (episilon), ɣA, ɣG, (gamma A &
G), δ (delta), β (beta); and a pseudogene (ψ).

Pseudogenes are non-functional copies of a gene and are considered

remnants of evolution.

α- cluster consists of three functional genes α1, α2 (alpha), ζ (zeta), and
four pseudogenes.

Hemoglobin is a tetramer formed by two alpha-like and two beta-like

polypeptides.
 Chromosomal aberrations
e.g. Hemoglobin gene family

Hemoglobin gene family provides developmental flexibility

Embryo Fetus Adult

α-like ζ α2 α2
β-like ε Aγ, Gγ β, δ (rare)

The various hemoglobin molecules used cater for the various oxygen
needs of embryo, fetus and adult. e.g. The fetus (small SA:V) derives
oxygen from the mother’s blood and a greater affinity to oxygen is required.

This is an example of developmental flexibility

β (beta- 99% of adult beta-type globin); δ (delta-1% of adult beta-type globin)

 Chromosomal aberrations
Duplications – Evolutionary significance
2. Hybrid genes
 Unequal crossing over between members of a multigene family
result in hybrid genes.
 This is a mechanism of gene evolution
e.g. A deleterious example is thalassemia (an inherited blood
disorder with anemic symptoms.
People with thalassemia have a hemoglobin subunit that is part δ and
part β (Lepore hemoglobin).

Some people have one that is part γ and part β (Kenya hemoglobin- no
thalassemia). The origin of these rare hemoglobin subunits can be
explained by unequal crossover
 thalassemia

Phenotypically normal-No thalassemia Little hemoglobin produced

Persistence of fetal hemoglobin

No phenotypic problems; no thalassemia

 Chromosomal aberrations
Duplications – Evolutionary significance
2. Gene clusters
 Cells need large amounts of certain gene products. Gene clusters
are a tandem array of duplicated genes that serve to increase gene
products. e.g. The nucleolar organiser in the human genome
consists of a tandem array of 250 rRNA genes.

 Another example: In humans, about 50 chromosomal sites

correspond to the different tRNA types, and each site contains
between 10 and 100 copies.

 Another example is the histone gene cluster. Histones are the most
abundant proteins in cells.
 Chromosomal aberrations
Duplications – Evolutionary significance
3. Permanent heterozygosity
 Heterozygosity of certain gene loci are associated with heterosis or
hybrid vigour. Heterozygosity cannot be fixed to an individual, since
heterozygous states would lead to segregation in future generations.

 Duplication provides a means of fixing heterozygosity.

A a
A

a A a
Single or double
a crossovers
A
1AA : 2 Aa : 1 aa
A a
 Chromosomal aberrations
Duplications – Evolutionary significance
4. Complementary genes and polygenes

 It is believed that complementary genes and polygenes, where a few

or many genes control character, originated through duplications.

5. Backup genes

 Duplication or redundancy is a way of backing up genes to provide

greater genome stability.
Chromosomal aberrations
Duplications – Evolutionary significance
6. Non-coding duplicated sequences (satellites)

 Non-coding duplicated sequences found in the centromeric and

telomeric regions provide stability to chromosomes. e.g. The
telomeric repeats are there to solve a functional problem that is
inherent in the replication of the ends of linear DNA molecules.

 Non-coding duplicated sequences along the chromosomes also

aid in chromosome pairing and recombination.

Satellites are important in DNA fingerprinting.