1 - Bioinformatics Flashcards
What is bioinformatics?
Computer based methods for understanding and predicting
- Functions
- Structures
- Evolution
of genes, genomes and proteins
Sequencing cost is dropping faster than Moore’s law
In general, what are pairwise alignments and multiple alignments for?
Pairwise alignment: finding motifs etc. which aid in the detection of close homologs (over 35% identity) and even
Multiple alignments: Patterns of conservation and phylogeny
What is partial homology?
Homology is all or nothing.
Partial homology is when different portions of a protein
It is difficult to prove non-homology, genes are either homologous or not known to be homologous (usually). You cannot prove non-homology from a common ancestral sequence.
When do mutations matter?
- If they occur in the germline
- The cell is unicellular and/or prokaryotic (except when there is a somatic macronucleus and germline micronucleus)
What is the difference between a mutation and a substitution?
What determines substitution rate?
Mutation: All changes in DNA that persist after replication in an individual organism
Substitution: A mutation that has reached fixation in a population
Substitution rate: dependent on both mutation rate and natural selective forces acting on mutatnts
What is positive selection?
Mutations that confer fitness advantage
RARE
What is purifying selection?
Also known as negative selection. Mutations that confer fitness disadvantages
FREQUENT
What is neutral evolution?
Genetic drift
Very important, as at some frequency it will lead to fixation due to random sampling effects.
Fixation of neutral changes is common and must be taken into consideration when sequencing.
VERY FREQUENT
What is the ‘nearly-neutral’ theory of molecular evolution?
This includes slightly advantageous and slightly deleterious mutations, which happen at about equal frequencies.
Most surprisingly, slightly advantageous mutations occur fairly often.
What are the two types of point mutations? Which occur more frequently?
Transitions: Purine to purine or pyrimidine to pyrimidine (4 kinds)
Transversions: Purine to pyrimidine (8 kinds)
Transitions occur much more frequently.
List the purines and pyrimidines
Purines: A + G
Pyrimidines: C + T
What is special about 3rd codon positions?
Mutations are usually synonymous (silent) due to the degenerate genetic code
This is not true for the 1st position (only 8 synonymous mutations in the 1st position, 126 in the third, NONE in the second)
Most nonsynonymous substitutions occur in the 2nd codon position, many in the first and few in the third.
List three very basic categories of sequence alignments
- Visual inspection
- Dot matrix method
- Algorithms
You are implicitly trying to determine what has happened to the sequences since their common ancestor
