Molecular Evolution and Phylogenies Flashcards
What are protein domains?
- Domains are distinct functional and/or structural units in a protein
- Usually, they are responsible for a particular function or interaction contributing to the overall role of a protein
- Similar domains can be found in proteins with different functions
Which domains are involved in protein-protein interactions?
Src homology 3 (SH3)
What are “sequence features”?
Sequence features are groups of amino acids that confer certain characteristics upon a protein and its function.
Give examples of sequence features
- Active sites
- Binding sites
- Post-translational modification (PTM) sites
- Repeats
What are “active sites”?
Contain amino acids involved in catalytic activity
What are “binding sites”?
Contain amino acids that are directly involved in binding molecules or ions
What are “PTM sites”?
Post-translational modification (PTM)
- Contain residues known to be chemically modified (phosphorylated, palmitoylated, acetylated etc.) after the process of protein translation
What are “repeats”
Typically short amino acid sequences that are repeated within a protein, may confer binding or structural properties upon it
For a mutation to have an effect on the phenotype, it must affect what?
For a mutation to have an effect on the phenotype, it must affect the structure, quantity or function of a protein
- Phenotypic changes can be subject to selection
How can you show that two proteins are homologous?
Make an alignment: Write the 2 sequences side-by-side so they match up as far as possible
What is the other term for an amino-acid sequence alignment?
Similarity matrix
Briefly describe the similarity matrix
- Similarity of the sequence between species indicates common ancestry of the gene
- Count of the difference indicates the MINIMUM number of nucleotide substitutions that must have occurred between two sequences
- Obtained numbers are conservative (UNDERESTIMATE of actual number of substitutions)
- Corrections for the underscoring are made using mathematical models
Briefly describe the Neutral Theory of Molecular Evolution (Motoo Kimura, 1968)
- Majority of mutations are severely neutral; neither advantageous nor disadvantageous
- If mutations are more (or less) frequent in a certain region of the genome compared to the neutral mutations, that indicates that the region is under selection (stabilising or positive)
- Many mutation are never observed because they are lethal, whereas neutral accumulate
- Natural populations of organisms harbour much more genetic variation than would be expected if genetic variation were influenced by natural selection alone
What is the “molecular clock”?
Evolution of a protein proceeds at a constant rate and therefore can be used as a clock
What is a “paralogue”?
Two or more homologous versions of a gene & protein, forming a gene (or protein) “family”
- These arose by a duplication of that part of the genome;
- Once duplicated, the 2 genes can evolve independently;
- This may lead to the evolution of new protein function
Briefly describe the homeobox gene family
Homeobox (HOX) proteins are “master switch” proteins that control development in all metazoan organisms
- The number of hox genes is between 1 & 13
- All hox genes are homologous.
- The hox system was created once, in early evolution.
Define “taxonomy”
The science of classification of organims
Define “systematics”
Encompasses nomenclature, classification and taxonomy
Define “phylogeny”
The history of descent of a group of organisms from a common ancestor
Define “phylogenetics”
Evolutionary relationships between organisms
What is the difference between a “character” and a “trait”?
A character is a feature of the organism, whereas a trait is a form of the character
What is a phylogenetic tree?
Phylogenetic trees are based on comparison of traits.
Individuals with common traits are placed together.
Traits inherited from a common ancestor are termed what?
homologous
Traits that differ from the ancestor are termed what?
derived
Define “homologies”
Traits that were present in the common ancestor
Define “homoplasies”
Similar characters in two or more taxa that are not derived from a common ancestor
What is “monophyletic taxa”?
Include ALL descendants of a common ancestor
What is “polyphyletic taxa”?
Include members with MORE THAN ONE recent common ancestor
What is “paraphyletic taxa”?
Include some, but not all, descendants of a common ancestor
What is the “outgroup”?
A lineage closely related to the focal group
What is the main problem with homoplasies?
Traits that appear similar but are not closely related through ancestry
What is “convergent evolution”?
Independent evolution of similar traits due to similar selection pressure (e.g. wings in birds and bats)
What is “parallel evolution”?
Independent evolution of common traits in organisms sharing distant relatives (e.g. patterns of butterfly wings)
What are “evolutionary reversals”?
The loss of a derived trait (e.g. limbs of snakes; teeth of frogs)
What are the advantages of molecular traits?
- They directly reflect the underlying process of evolution; changes in the hereditary material
- There are a vast number of potential traits
- They can detect differences between very closely related organisms (even those that show not phenotypic difference)
- They are not affected by the environment (unlike some morphological traits)
- Since mutations generally occur as random events with specific probabilities, the number of mutations can be used to calibrate evolutionary time (molecular clocks)
What is a synonymous substitution?
- Those that do not change the amino acid that is specified by the gene
What is a non-synonymous substitution?
- Those that change the amino acid chain specified
What is a nonsense substitution?
Those that prematurely terminate the gene.
What makes molecular clocks possible?
- The rate of fixation of neutral mutations is equal to the neutral mutation rate
- Thus, sequences diverge in evolution at a constant rate
- Thus, the divergence between two sequences can be used to say when the two organisms diverged from each other
Which phenomena demonstrate the limitations of molecular clocks?
- Not all mutations are neutral
- Not all loci change at the same rate
- Transitions are more common than transversions
- Rates are strictly based on generations (not years) and reproductive rates vary between species
What is the C-value?
The weight of the genome (in g)
What is “polypoidy”?
More than 2 copies of the haploid chromosomes.
- Many bony fish are polyploids. Polyploidy is common in plants.
What is “euploidy”?
Containing a chromosome number that is a multiple of the haploid number
What is “aneuploidy”?
Extra or fewer copies of one chromosome or part of chromosome.
- Common cause of miscarriage in humans e.g. trisomy occurs in about 35% of embryos of women over 40
What is a transposon?
One type of repeating DNA.
- A transposon can move at random throughout a genome. It is cut out of its site and reinserted into another site by the action of a transposase, which the transposon codes for.
What is a retrotransposon?
Mobile DNA elements that can increase in copy number via the production of an RNA intermediate followed by insertion of a DNA copy into the genome.
Gene duplication occurs by two different processes. What are they?
- One is duplication of large parts, or whole chromosomes, or even the whole genome (the latter leads to polyploidy)
- The other is the duplication of short sections of sequence due to e.g. replication slippage
What is a pseudogene?
A section of a chromosome that is an imperfect copy of a functional gene.
Briefly describe “Housekeeping”, “Accessory/Supplementary” functions of genes
“Housekeeping” functions:
- Cell structure
- Replication, transcription, translation
- Metabolism
“Accessory/Supplementary” functions:
- Virulence
- Antibiotic resistance
- Metabolism - rare substrates
With regards to gene acquisition, name the three ways in which DNA can move between cells in bacteria.
- Transformation
- Bacteriophage
- Plasmids
With regards to gene acquisition, name the three ways in which DNA can move within cells in bacteria.
- Transposable elements
What is “transformation” in bacteria?
- Uptake of free DNA from the environment
- DNA recombined into genome; cell acquires new gene(s)
What is the bacteriophage?
- Phage can move genes between strains/species
- Harbour “accessory” functions
- Transduction; phage aberrantly transports non-phage DNA Bacterial DNA transferred to new cell
Which observable characters are used in phenotypic methods to identify bacterial species?
- Morphological
- Physiological
- Biochemical
Briefly describe genomic DNA homology as a genotypic method to identify bacterial species
- Isolates are evolutionarily close to each other when their DNA is highly homologous; e.g. same species
- Isolates are evolutionarily distant to each other when their DNA is less homologous; e.g. different species
What genotypic methods do we use to “type” strains of bacteria?
- DNA based; characters are heritable and stable; unaffected by culture conditions
- Restriction enzyme site polymorphisms;
RFLP: Restriction Fragment Length Polymorphisms - DNA sequence methods
What does RFLP stand for?
Restriction Fragment Length Polymorphisms
Briefly describe RFLP methods
- Extract DNA
- Digest with restriction enzyme (RE)
- Agarose gel electrophoresis to separate DNA fragments by length; whole genome RE fragment analysis (PFGE); Probe for a multicopy DNA sequence
What does MLST stand for?
MultiLocus Sequence Typing
Briefly describe MLST
Compare isolates using DNA sequences:
- Use housekeeping genes (usually 7); Ubiquitous, unlike accessory genes; sequences more stable than accessory gene sequences
Each new sequence of a gene (allele) given a code number
Strains identified (typed) by their different 7-digit codes
What are “panmitic species”?
Species that have achieved genetic diversity by mutation AND horizontal gene transfer
What are the three sources of bacterial genomic diversity?
- Mutation, rearrangement, deletions
- Horizontal gene transfer within species
- Horizontal gene transfer between species
Fitter strains of bacteria become more abundant. How?
- Clonal expansion of fitter strains
- The genes/alleles in these strains become more frequent in the population
Describe the “species-strain” boundary
Much overlap in characters between strains
Describe the “species-species” boundary
Little overlap in characters between species
