This document discusses exon shuffling, which is a mechanism by which new genes can form through the rearrangement of exons from different genes. Exon shuffling was first proposed in 1978 and involves recombination within introns that allows exons to be assorted independently, generating new exon combinations. There are three main types of exon shuffling: exon duplication, insertion, and deletion. Exon shuffling generates genetic variation and mosaic proteins, and it has played a major role in evolution. The mechanisms involved are crossover during sexual recombination and transposon-mediated movements that can cut, paste, or copy and paste exons into new locations.

2. Amna Shoukat (7211)Amna Shoukat (7211)
Amina Bashir (7227)Amina Bashir (7227)
Faiqa Zafar (7259)Faiqa Zafar (7259)
4th Semester BS(Hons)4th Semester BS(Hons)
Dept. of BioinformaticsDept. of Bioinformatics
& Biotechnology& Biotechnology
Govt. College university,Govt. College university,
FSDFSD

3. scheme of presentationscheme of presentation
What is Exon Shuffling?What is Exon Shuffling?
HistoryHistory
Theories about appearance of introns eukaryotesTheories about appearance of introns eukaryotes
The structure of genesThe structure of genes
Types of Exon ShufflingTypes of Exon Shuffling
Generating Genetic VariationGenerating Genetic Variation
MosaicMosaic (or(or chimericchimeric)) proteinprotein
Mechanisms involved in Exon ShufflingMechanisms involved in Exon Shuffling
The study of exon shuffling asThe study of exon shuffling as
an evolutionary driving forcean evolutionary driving force
ReferencesReferences

4. What is Exon Shuffling?What is Exon Shuffling?
Exon shuffling is a molecular
mechanism for the formation
of new genes. It is a process
through which two or more
exons from different genes
can be brought together
ectopically, or the
same exon can be duplicated,
to create a new exon intron
structure.

5. HistoryHistory
Exon shuffling was first introduced in 1978
by Walter Gilbert
existence of introns could play a major role in the
evolution of proteins.
It was noted that recombination within introns could
help assort exons independently.
repetitive segments in the middle of introns could
create hotspots for recombination to shuffle the
exonic sequences.

6. Theories about appearance ofTheories about appearance of
introns eukaryotesintrons eukaryotes
Two theories.Two theories.
Introns Early
Introns Late
Introns EarlyIntrons Early
introns and RNA splicing were the relics of the RNA world and
therefore both prokaryotes and eukaryotes had introns in the
beginning. However, prokaryotes eliminated their introns in
order to obtain a higher efficiency, while eukaryotes retained
the introns and the genetic plasticity of the ancestors.

7. Introns LateIntrons Late
prokaryotic genes resemble the ancestral genes and
introns were inserted later in the genes of
eukaryotes.
eukaryotic exon-intron structure is not static, introns
are continually inserted and removed from genes and
the evolution of introns evolves parallel to exon
shuffling.
exon shuffling to start to play a major role in protein
evolution the appearance of spliceosomal introns had
to take place

8. This was due to the fact that the self-splicing introns of the RNA
world were unsuitable for exon-shuffling by intronic
recombination. These introns had an essential function and
therefore could not be recombined
there is strong evidence that spliceosomal introns evolved fairly
recently and are restricted in their evolutionary distribution.
Therefore exon shuffling became a major role in the
construction of younger proteins.
studies suggested that there was an inverse relationship
between the genome compactness and the proportion of
intronic and repetitive sequences. As well as the fact that exon
shuffling became significant after metazoan radiation.

9. The structure of genesThe structure of genes
Many forms of genes.Many forms of genes.
Structural gene
Regulatory gene
Housekeeping gene
Tissue specific gene
Whatever their function, all genes contain a coding
region which specifies a polypeptide or an RNA
molecule

10. Structure of a typical geneStructure of a typical gene
Exon 1Exon 1 Exon 2Exon 2 Exon 3Exon 3 Exon 4Exon 4
Intron 1Intron 1 Intron 2Intron 2 Intron 3Intron 3
5’5’ 3’3’
EukaryoteEukaryote
ProkaryoteProkaryote
5’5’ 3’3’
Stop codonStop codonInitiation codonInitiation codon
RegulatoryRegulatory
sequencessequences
RegulatoryRegulatory
sequencessequences
Initiation codonInitiation codon Stop codonStop codon

11. Types of Exon ShufflingTypes of Exon Shuffling
3 Types3 Types
Exon Duplication
Exon Insersion
Exon deletion
exon duplicationexon duplication
The duplication of one or more exons within a gene (internal duplication)
exon insertionexon insertion
Exchange of domains between genes or insertions into a gene
exon deletionexon deletion
The removal of a segment from a gene.

12. Generating Genetic VariationGenerating Genetic Variation
Gene DuplicationGene Duplication
Almost every gene in the vertebrate genome exists in
multiple copies
Gene duplication allows for new functions to arise without
having to start from scratch
Studies suggest the early in vertebrate evolution the entire
genome was duplicated at least twice
Exon DuplicationExon Duplication
Duplications are not limited to entire genes
Proteins are often collections of distinct amino acid domains
that are encoded by individual exons in a gene
The separation of exons by introns facilitates the duplication
of exons and individual gene evolution

13. Exon and Gene DuplicationExon and Gene Duplication
from Unequal Crossing Overfrom Unequal Crossing Over

14. Mosaic (or chimeric) protein
A protein encoded by a gene that contains regions
also found in other genes. The existence of such
proteins provides evidence of exon shuffling.
exon shufflingexon shuffling
↓↓
mosaic proteinsmosaic proteins

15. Mechanisms involved in ExonMechanisms involved in Exon
ShufflingShuffling
Transposon
mediated
2 Mechanisms involved2 Mechanisms involved
CCrossover duringrossover during
sexualsexual
recombinationrecombination
of parental genomeof parental genome
TranposonTranposon
mediatedmediated

16. Crossover during sexual recombination ofCrossover during sexual recombination of
parental genomesparental genomes
3 Steps involved3 Steps involved
The first stage is the insertion of introns at positions
that correspond to the boundaries of a protein domain.
The second stage is when the “protomodule”
undergoes tandem duplications by recombination
within the inserted introns.
The third stage is when one or more protomodules are
transferred to a different nonhomologous gene by
intronic recombination

17. Crossover during sexualCrossover during sexual
recombination of parental genomesrecombination of parental genomes

18. Transposon mediatedTransposon mediated
LongLong
interspersedinterspersed
element (LINE)-element (LINE)-
11
Exon Shuffling viaExon Shuffling via
TranspositionTransposition
Copy & pasteCopy & paste
Exon ShufflingExon Shuffling
viavia
TranspositionTransposition
Cut & PasteCut & Paste
Many types:Many types:

19. Long interspersed nuclear elementLong interspersed nuclear element
(LINE)-1(LINE)-1
The mechanism of LINE. LINE primary transcripts
are translated into the ORF1 and ORF2 gene
products in the cytosol. The RNA then returns to the
nucleus with the ORF1 & 2 proteins. These enzymes
catalyze reverse transcription and integration of the
LINE element at AT-rich regions of genomic DNA.
The poly(A) tail of the LINE RNA is used for selection
of integration sites. SINE element retrotransposition
is thought to be mediated by the ORF1 & 2 proteins
encoded by LINEs.

20. Long interspersed elementLong interspersed element
(LINE)-1(LINE)-1

21. Exon Shuffling via TranspositionExon Shuffling via Transposition
Cut & pasteCut & paste
Exon shuffling can also occur via cut-and-paste
transpositions mediated by DNA transposons. It
requires that two copies of the transposon flank the
target exon. Both DNA transposons and the exon will
move as one piece of DNA if the transposase
happens to cleave DNA at the left inverted repeat of
the upstream transposon and at the right inverted
repeat of the downstream transposon. Gene 1 ends
up losing the exon, and Gene 2 acquires the exon

22. Exon Shuffling via TranspositionExon Shuffling via Transposition
Cut & pasteCut & paste

23. Exon Shuffling via TranspositionExon Shuffling via Transposition
Copy & pasteCopy & paste
Exons can move along with a LINE element when it
transposes via its copy-and-paste mechanism When
a LINE element has a weak poly(A) signal, RNA
polymerase II continues to transcribe downstream,
potentially through an exon. If this exon has a strong
poly(A) signal, then transcription stops and the RNA
is polyadenylated. Then following the mechanism i,
DNA encoding the exon and the LINE element can be
incorporated into another gene.

24. The spliced mRNA produced from the acceptor gene may
contain the newly introduced exon. Exon shuffling is
supported by experimental evidence and the enormous
amount of interspersed repeat DNA in genomes. Over
billions of years, it has played a major role in evolution of
genomes.

25. The study of exon shuffling asThe study of exon shuffling as
an evolutionary driving forcean evolutionary driving force
Highly bioinformatics drivenHighly bioinformatics driven
one can look for duplications, retrotranspositions,
transposable elements,
Genetic engineering approaches to trace
evolutionary developments

26. References
https://www.google.com/search?
client=opera&q=scheme+of+presentation&sourceid=opera&ie=
UTF-8&oe=UTF-8#q=exon+shuffling
Wang, W., Zheng, H., Fan, C., Li, J., Shi, J., Cai, Z., . . . Wang,
J. (2006). High rate of chimeric gene origination by retroposition
in plant genomes. Plant Cell, 18(8), 1791-1802. doi:
tpc.106.041905 [pii] 10.1105/tpc.106.041905
Origins of New Genes: Exon
Shuffling
By Carl Hillstrom