Introduction to bioinformatics
Hoorcollege 3 – 15 januari 2024
Alignments
Introduction: DNA, proteins and mutations
DNA is a macromolecule. Big molecule with small units
Bases: Adenine, Guanine, Thymine, Cytosine
FASTA format
Each sequence begins with the symbol “>”
First line is the sequence description and following lines until next header are the protein (or
nucleotide) sequence
Central dogma of molecular biology
From DNA to RNA to proteins
Transcription and translation
RNA divides in codons
The codon table
Which combination of nucleotides are which amino acid
Stopcodon: translation stops
Mutation: change in DNA sequence
Reference genome (GRCh38)
- 3x109 base pairs
- 20 000 proteins coding genes
- 1,5% coding
- 3.7x1013 cells
Point mutation: one base is changed
SNV = single nucleotide variant
- A position in the DNA where a person/cell has a different nucleotide than the
reference genome
SNP = single nucleotide polymorphism
- A position in the DNA where a change is present in at least 1% of the population
, Types of mutations
Nt change :
- Transition A G or T C
o Niet dezelfde groep
- Transversion A/G T/C oftwel A T or G C
o Dezelfde groep
Aa change:
- Synonymous TTC TTT
o does not result in a change to the amino acid sequence of the
protein
- Nonsynonymous
o result in a change to the amino acid sequence of the protein
o Nonsense TTC ATC
Ontstaat een stopcodon
o Missense
A substitution that results in a change in the amino acid
sequence of a protein
Conservative TTC TCC
amino acid is replaced by a different amino acid with
similar chemical properties
Non conservative TTC TGC
Substitution has different properties
Al of this is a point mutation, only one base changes
Insertion and deletion cause frameshifts
Alle opvolgende condons zijn hierdoor veranderd
Quiz: which change a frameshift?
Deletion of 2 nucleotides: yes rest changes
Insertion of 3 nucleotides: no only when it’s a stopcodon, but that is not a frameshift
Insertion of 4 nucleotides: yes rest changes
Evolution, phylogeny and alignments
Mutations are random
Most mutations are nearly neutral genetic drift as driver of molecular evolution
Genetic diversity together with selection are the driving forces of adaptative evolution
Phylogenetic tree: branching diagram that describes evolutionary relationships
Hoorcollege 3 – 15 januari 2024
Alignments
Introduction: DNA, proteins and mutations
DNA is a macromolecule. Big molecule with small units
Bases: Adenine, Guanine, Thymine, Cytosine
FASTA format
Each sequence begins with the symbol “>”
First line is the sequence description and following lines until next header are the protein (or
nucleotide) sequence
Central dogma of molecular biology
From DNA to RNA to proteins
Transcription and translation
RNA divides in codons
The codon table
Which combination of nucleotides are which amino acid
Stopcodon: translation stops
Mutation: change in DNA sequence
Reference genome (GRCh38)
- 3x109 base pairs
- 20 000 proteins coding genes
- 1,5% coding
- 3.7x1013 cells
Point mutation: one base is changed
SNV = single nucleotide variant
- A position in the DNA where a person/cell has a different nucleotide than the
reference genome
SNP = single nucleotide polymorphism
- A position in the DNA where a change is present in at least 1% of the population
, Types of mutations
Nt change :
- Transition A G or T C
o Niet dezelfde groep
- Transversion A/G T/C oftwel A T or G C
o Dezelfde groep
Aa change:
- Synonymous TTC TTT
o does not result in a change to the amino acid sequence of the
protein
- Nonsynonymous
o result in a change to the amino acid sequence of the protein
o Nonsense TTC ATC
Ontstaat een stopcodon
o Missense
A substitution that results in a change in the amino acid
sequence of a protein
Conservative TTC TCC
amino acid is replaced by a different amino acid with
similar chemical properties
Non conservative TTC TGC
Substitution has different properties
Al of this is a point mutation, only one base changes
Insertion and deletion cause frameshifts
Alle opvolgende condons zijn hierdoor veranderd
Quiz: which change a frameshift?
Deletion of 2 nucleotides: yes rest changes
Insertion of 3 nucleotides: no only when it’s a stopcodon, but that is not a frameshift
Insertion of 4 nucleotides: yes rest changes
Evolution, phylogeny and alignments
Mutations are random
Most mutations are nearly neutral genetic drift as driver of molecular evolution
Genetic diversity together with selection are the driving forces of adaptative evolution
Phylogenetic tree: branching diagram that describes evolutionary relationships
