Molecular Evolution Flashcards
What is creationism?
Idea that species are made by a supernatural creator
What does science assume for everything?
That there are natural explanations for everything.
What is the basis of scientific theory?
Predicts must be tested and confirmed/ refuted with data
What is Darwin’s Theory of evolution by natural selection?
Spontaneous natural variation occurs and they are stably inherited
What evidence is there for Darwin’s TOEBNS?
Man and apes descend from a common ancestor, so there must be intermediate fossils present (which there are + early homo-sapiens have been found too)
What is the modern synthesis?
Darwin’s theory and mendelian genetics are linked
Is Darwin’s theory a hypothesis?
No it is a knowledgeable deduction based on evidence
What is variation?
Mutation - change in DNA sequence
What is the common cause of mutations occurring? How common are mutations?
Mistakes during DNA synthesis although this is rare since DNA synthesis is accurate (DNA polymerase’s proof reading means it goes back and corrects mistakes)
What type of mutations are most of them?
Neutral or harmful; only some are beneficial
What are individuals in competition with?
Predators, prey and individuals of their own species
What is the effect of new alleles on reproductive success?
They can increase/ decrease it
What is relative fitness (w)? What is it compared with?
The average number of surviving offspring of a particular genotype after one generation
It is compared with competing genotypes
What does w<1 indicate?
That the frequency of the allele will decrease with each generation until the allele disappears (strong negative selection)
What does w>1 indicate?
That the frequency of the allele will increase with each generation until the allele reaches fixation (only allele left since the other alleles have been misplaced) (strong positive selection for an allele = fixation)
Does fixation realistically occur?
No - instead you get a mixture of multiple alleles
What are 3 types of small mutation?
Base substitutions and small insertions/ deletions
What are 4 types of large mutation?
- Insertion of transposable elements (parts of genome that cut out of one place and insert into another) / viral insertions (retroviruses that are then stably inherited)
- Large DNA duplications
- Large deletions
- Chromosome rearrangements
What would be a difference between species with a more recent common ancestor vs. species with a more distant common ancestor?
Species with a more recent common ancestor have fewer differences in their DNA sequences (since there has been less time to allow for DNA mutations to occur in their sequences)
What are antibiotics?
Substances that are toxic to bacteria but not fungi (they are produced from fungi)
Why our fungi humans cousins?
They are closely related to humans than plants
What can DNA sequence data of animals be used for?
To generate family trees
How was HIV theorised to be introduced into the human population?
A contaminated batch of polio vaccine (which was grown on culture monkey cells)
When comparing sequences of 2 species why are there more differences found in introns than exons?
Introns are not protein coding sequences of DNA, but exons are. If a mutation occurs in an exon it is more likely to mess up a protein so is removed by negative selection where as introns are less important to remove
When comparing sequences of 2 species why are there more differences in the 3rd nucleotide of every amino acid as opposed to the other 2?
The first 2 nucleotides are important in defining the amino acid where as the 3rd nucleotide is redundant so a change in it will not change the amino acid sequence
What does a base insertion cause? What do this often result in?
It causes a change in the amino acid from that point on and so a frame shift - often results in a premature stop codon. Frame shifts almost always stop a protein from forming and are negatively selected and removed
What is the severity of a 3 base insertion versus a normal insertion?
A 3 base insertion adds an extra amino acid rather than changing them all; this could lead to a problem but is far less drastic to a normal insertions complete frame shift
What is the difference between a synonymous and non-synonymous substitution?
A synonymous insertion does not change the amino acid but a non-synonymous insertion does
What kind of sequences are highly, moderately and weakly conserved
Active sites of enzymes and structural regions of proteins are highly conserved
Signal regions in 5’ and 3’ UTRs and promoters are moderately conserved
Enhancers (in introns/ intergenic DNA) and other intronic/ intergenic DNA is weakly conserved (since a lot of the mutations that occur in these regions do not have an effect)
An intergenic region is a region of DNA between genes
What kind of alteration to genes is a major driving force of evolution?
Gene duplication, since the original gene can maintain the original function and the copied gene can evolve new functions (by altering the coding and control sequences)
What gave rise to myoglobin, Hb and then the Hb subtypes?
Duplication originally arising from an ancestral gene
What sets the start of the reading frame?
The first codon - AUG
What are the differences between myoglobin and haemoglobin? Mention where there is expression of them, how many subunits the protein has, the shape of the oxygen dissociation curve and it’s function
Myoglobin - expressed in skeletal muscle; monomeric protein; hyperbolic oxygen dissociation curve (only gives up oxygen at very low oxygen concentrations); stores oxygen
Hb - expressed in RBCs; tetrameric protein; sigmoidal oxygen dissociation curve (gives up and takes up oxygen readily in order to suit it’s function); oxygen transport
Where are the alpha globin gene complex and beta globin gene complex found?
Alpha - chromosome 16
Beta - chromosome 11
How did all the different types of Hb form?
The ancestral gene duplicated to form myoglobin and Hb genes
The Hb gene duplicated to form alpha and beta globin genes
The alpha globin genes duplicated to form embryonic and adult genes whereas the beta globin genes duplicated to form embryonic, foetal and adult genes
Why do we have foetal Hb?
Helps the foetus grab oxygen across the placenta from the mother
What are the subunit compositions of all the 5 forms of Hb?
Adult Hb - HbA - alpha 2 beta 2
Adult Hb - HbA2 - alpha 2 delta 2 (also known as minor adult Hb since we have less than 1% of it)
Foetal Hb - HbF - alpha 2 gamma 2
Embryonic Hb - Hb Gower 1 - zeta 2 epsilon 2
Embryonic Hb - Hb Gower 2 - alpha 2 epsilon 2
Not tested on the embryonic Hbs
How did the gamma globin gene change in order to function in HbF?
The gamma globin gene had changes to it’s amino acid sequence in order to increase it’s affinity for oxygen
How many gamma globin genes are there and do they produce different proteins?
There are 2 gamma globin genes and the proteins they produce are not functionally different. It is expressed in foetal life.
What also occurs when duplication of the gamma gene for foetal Hb is happening?
An alteration of regulatory sequences so that the gamma Hb genes are expressed by the foetus and beta Hb expressed post natally
How are the beta and gamma globin genes differentially expressed?
During the duplication phase, the promoter for the globin genes duplicates along with the coding sequence.
The promoter, LCR, interacts with TFs which cause it to interact with the gamma gene promoter to cause gamma globin expression.
Upon birth, different TFs interact with the LCR, causing it to interact with the beta globin gene promoter instead
What are pseudogenes? Where are they found?
Sequences of DNA that have lost their function i.e. cannot make a functional protein as it has stop codons/ mutations in key regulatory sequences
There are many of them found across the genome, but they are lost over time since there is no need to conserve them
Give an example of a pseudogene
Pseudo beta, sharing sequence homology with a beta globin gene but has lost function
What are some examples of genetic diseases?
Fanconi’s Anaemia, SCA, beta thalassaemia, cystic fibrosis
What is Fanconi’s anaemia?
A recessive genetic disorder The gene arises by random mutation It has a low allele frequency And is eliminated by natural selection Causes most children to die young (bone marrow failure during childhood) + cannot reproduce if they grow up
What is SCA?
A genetic disorder
Point mutation in the beta globin gene
Where there is a single a.a. substitution of glutami acid by valine at position 6
Causes Hb molecules to aggregrate and form crystals when deoxygenated, forcing the RBCs to form a sickle shape
What do the crystals in SCA do?
Damage the red cell membrane resulting in cell lysis, causing anaemia, and cell adhesion, causing blockage of small blood vessels leading to tissue infarction
What is a benefit of being a heterozygote of SCA?
You are much less likely to die of malaria
