molecular evolution Flashcards
What is molecular evolution?
- Charles Darwin (1859)
- based on natural selection and fitness
- explains the current variety of life on earth
What is natural selection?
-the effects of a wide range of factors on the frequency of heritable changes in a species.
What is fitness?
- how well species are able to reproduce in its environment.
- anything that increases fitness is selected.
what is modern synthesis theory?
- theory that explains evolution could be unified with genetics to explain the molecular process underlying evolution.
- genetic variation is the main source of heritable changes in a species.
what factors affect frequencies of genetic variants?
- selection
- mutation
- migration
- genetic drift
What is selection?
-genetic variants that confer a positive advantage will be selected for, and vice versa.
give examples of variants that confer a positive advantage in selection.
-resistance to disease
-ability to metabolise a new food source
antibiotic resistance
-change in appearance that enhances mate chance.
Why are some parts of the genome resistant to change, give an example?
- Some parts of genome are resistant to change because they contain vital sequences which need to be conserved.
- Example : DNA that encodes active site of enzyme
- conserved = dont change through time
Define mutation
- process by which variation in the genome arises
- genomic variants and their frequency depends on selection and when they first arose.
- a rare variant may arise due to base deletion(because it is disadvantageous) and being selected against.
Define migration.
- physical movement of people from different population results in new pools of variant being introduced to an existing population (admixture).
- change in population can be due to admixture, not always due to disease.
Define genetic drift.
- how frequency of a variant changes in a population due to chance.
- not all organisms in population will pass on their genetic variant (one gene from each parent not both)
- recombination will also result in not all variants being passed on
- all variants are subject to genetic drift
What is sequence conservation?
- DNA sequence that is vital to the survival of an organism does not normally show much evidence of variation
- most variants in these regions will be selected against as they are likely to have strongly deleterious effect.(disadvantage)
- flexibility for sequence conservation due to the variation in the third base of a codon codes for same amino acid, so same protein will be coded.
What are 3 levels of conservation?
- high conservation : coding regions (not exons as these contain non-coding regions)
- intermediate conservation - prometer, 5’ untranslated region (UTR), 3’ UTR, terminator.
- low conservation : introns, 3rd base of codons , terminator.
What can we use sequence conservation for?
- cross species comparison : generate an evolutionary profile for a gene or gene family
- cross -species conservation allows us to identify the important regions of a gene (and its protein)
Define phylogenetics
‘tree of life’
-incorporates all living things on earth and tries to show their relatedness in terms of evolution.
what are 4 steps of studying phylogenetics?
- observe sequence
- reconstruct evolutionary history
- learn more about evolutionary processes
- develop better evolutionary models.
What does the distance between two entities on the tree show?
- how similar they are
- distance is related to evolutionary pressures and time.
- time is estimated by mutation rate
what are uses of phylogenetic in disease?
- it had been theorised that HIV had been introduced to human population via a contaminated polio vaccine in Africa.
- Worobey et al (2004) investigated this using phylogenetic
- sampled HIV and SIV of humans and chimpanzees
- found : polio vaccine does not give HIV bc evolutionary distance
What is unequal crossing over?
recombination between sequences are not the correct sequence but are very similar
-often low copy number repeat sequence
Give an example of globin gene.
- two clusters
- alpha like and beta like
What chromosome are alpha like and beta like genes found?
- alpha like are on chromosome 16- 3 genes and 3 pseudogenes
- beta like are on chromosome 11 - 5 genes and 1 pseudogene
What order are globin genes arranged?
- genes are arranged in the order of expression during development.
What are pseudo genes?
- non functioning genes that look similar to functioning genes but are non functioning.
- complicate PCR/sequencing
What are symptoms of sickle cell disease?
anaemia - fatigue, restlessness, jaundice
- acute pain episode
increased frequency of infection - spleen damage
What is the genetics of sickle cells?
- a single base change in the beta -globin gene haemoglobin
- codon change is a GAG to GTG
- this is Glu to Val in position 6
- on chromosome 11
- autosomal recessive gene
What is the chance of a child having SCD if parents have one copy of the the gene (Ss)?
1/4 chance of child having 2 copies = sickle cell
Why is sickle cell more common in African, middle eastern and Indian population?
natural selection and sickle cell:
- two copies has extremely negative effects on reproductivity (bc it causes sickle cell disease)
- one copy of HbS variant helps resistance of severe malaria
- this heterozygous advantage means that HbS variant is maintained in the population when it would have otherwise been selected against.
What does hemoglobin consist of?
- 2 alpha proteins
- 2 beta proteins
Define gene duplication.
- duplication of a DNA sequence consisting a gene.
What causes gene duplication?
- the typical mechanism is unequal crossing over during meiosis
What happens after duplication?
- one copy can continue the original function
- the other copy can evolve new functions through changes in the coding sequence and control sequences.
What does globin cluster evolution show?
- globin genes have evolved through duplication and accumulation of mutations (divergence)
- some are functioning genes and some are pseudogenes
- divergence of promoters has occured so they bind different transcription factors and allow expression of genes at different stages of development (embryo > feotus > postnatal) .
