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DNA Basics: Genetic Information Stored in DNA Molecules
1.
2.
3. Basic Biology: DNA
Genetic information is stored in
deoxyribonucleic acid (DNA)
molecules.
A single DNA molecule is a sequence
of nucleotides
adenine (A)
cytosine (C)
guanine (G)
thymine (T)
nitrogenous
base
pentose
sugar
phosphate
Nucleotide DNA molecule
4. Basic Biology: DNA
Paired DNA strands are in
reverse complementary
orientation.
One in forward, 5’ to 3’ direction
The other in reverse, 3’ to 5’
direction
Both strands are
complementary.
A pairs with a T
G pairs with a C
forward
strand
reverse
strand
5’
3’
3’
5’
Image modified with the permission of the
National Human Genome Research Institute
(NHGRI), artist Darryl Leja.
5. Basic Biology: Genome
• The genome is the
entire hereditary
information of an
organism.
• Genomes are
partitioned into
chromosomes.
• A chromosome can
be linear
(eukaryotes), or
circular
(prokaryotes). Image modified with the permission of the
National Human Genome Research Institute
(NHGRI), artist Darryl Leja.
7. Changes in Genomic Sequences
Genomes of different species (even of
closely related individuals) differ from
one another.
These differences are caused by
point mutations, in which only one
nucleotide is changed, and
genome rearrangements, where multiple
nucleotides are modified.
8. Point Mutations
Insertion …ATGGCG… → …
ATGTGCG…
Deletion …ATGTGCG…→ …
ATGGCG…
Substitution …ATGTGCG… → …
ATGCGCG…
…ATG-GCATGTGCGATGTGCG…
…ATGTGCATG-GCGATGCGCG…
DNA sequence alignment showing matches, mismatches,
and insertions/deletions
10. Reversal:
A reversal is an operation that transforms one
signed permutation into another, reversing the
order or a contiguous protein and flipping the
sign.
Translocation:
It is process of exchange of genetic material
between chromosomes. A balanced translocation
results in no gain or loss of material.
Furthermore, while an unbalanced translocation
may result in trisomy or monosomy of a
particular chromosome segments.
11. Fission:
It is the division of a single entity into two or
more parts and then regeneration of those parts
into separate entities resembling the original.
Fusion:
It is the process in which several unicellular cells
combine to form a multinuclear cell.
13. Signed Reversals
5’ ATGCCTGTACTA 3’
3’ TACGGACATGAT 5’
5’ ATGTACAGGCTA 3’
3’ TACATGTCCGAT 5’
Break
and
Invert
Taken and modified from An Introduction to Bioinformatics Algorithms by Neil Jones and Pavel Pevzner
14. Levenshtein’s Edit Distance
Let A and B be two sequences
(genomes). The minimum number of
edit operations that transforms A into B
defines the edit distance, dedit, between
A and B.
Possible edit operations:
point mutations
genome rearrangements
15. A Word Puzzle
To transform a start word into a target
word, change, add, or delete characters
until the target is reached.
Example: start “spices” target “lice”:
○ spices → slices → slice → lice
○ spices → spice→ slice→ lice
16. Edit Distance Using Point
Mutations
S1=AGCTT, S2=AGCCTG, S3=ACAG
AGCTT AGCTG AGCCTG
⇒ dedit(S1,S2) = 2
AGCTT AGCTG AGCAG ACAG
⇒ dedit(S1,S3) = 2
AGCCTG AGCTG AGCAG ACAG
⇒ dedit(S2,S3) = 2
T→G insert C
T→G T→A delete G
delete C T→A delete G
17. Edit Distance and Evolution
The edit distance is often used to infer evolutionary
relationships.
Parsimony assumption: the minimum number of changes
reflects the true evolutionary distance
Parsimonious phylogeny inferred from edit distances
18. Levenshtein’s Edit Distance
Let A and B be two sequences
(genomes). The minimum number of
edit operations that transforms A into B
defines the edit distance, dedit, between
A and B.
Possible edit operations:
point mutations
genome rearrangements
19. Rearrangements and Anagrams
An anagram is a rearrangement of a
word or phrase into another word or
phrase.
○ eleven plus two → twelve plus one
○ forty five → over fifty
Please visit the Internet Anagram web
server at
http://wordsmith.org/anagram/.
21. Genome Comparison: Human -
Mouse
Humans and mice
have similar genomes,
but their genes are in a
different order.
How many edits
(rearrangements) are
needed to transform
human into mouse?
245 rearrangements
Taken and modified from An Introduction to Bioinformatics Algorithms by Neil Jones and Pavel Pevzner
22. Transforming Mice into Humans
a) Mouse and
human share a
common ancestor
b) They share the
same genes, but in a
different order
c) A series of
rearrangements transforms
one genome into the other
23. Web Tools
GRIMM Web Server
computes signed and unsigned reversal
distances between permutations.
Cinteny
a web server for synteny identification and
the analysis of genome rearrangement
24. DCJ Genome Rearrangements
The DCJ model uses Double-Cut-and-
Join genome rearrangement operations.
DCJ operations break and rejoin one or
two intergenic regions (possibly on
different chromosomes).
25. Genome Representation
In the DCJ model, a genome is
grouped into chromosomes
(linear/circular).
A gene g on the forward strand
is represented by [-g,+g]
A gene g on the reverse strand
is represented by [+g,-g]
Telomeres are represented by
the special symbol ‘o’.
An adjacency (intergenic
region) is encoded by the
unordered pair of neighboring
gene/telomere ends.
Example.
linear c1=(o 1 -2 3 4 o)
circular c2=(5 6 7)
26. Research paper on DCJ rearrangements
http://www.lirmm.fr/~rivals/CoCoGEN/articles/B
erard_RECOMBCG08.pdf
Editor's Notes
Redo this slide. Have a look at http://lib.bioinfo.pl/courses/view/693