Molecular Evolution Flashcards
What is Evolution?
On the origin of species
- A theory put forward to explain the current variety of life on earth
- Natural selection and Fitness
- Underpins our understanding of biology
Define “Natural Selection”
The effects of a wide range of factors on the frequency of heritable changes in a species
Define “Fitness”
How well a species is able to reproduce in its environment.
Anything that increases fitness is selected for, anything that deceases fitness is selected against and other neutral changes will vary randomly.
Describe the modern synthesis
- It was realised that evolution could be linked to genetics to explain modular processes underlying evolution
- Genetic variation is the main source of heritable changes in a species
- Frequencies of genetic variants are affected by:
Selection, Mutation, Migration, Genetic Drift
Describe how Selection affects genetic variants
- Genetic variants that confer a POSITIVE advantage will be selected for (and vice versa)
- Examples of + advantages include resistant to disease, ability to metabolise new food source, antibiotic resistance.
- Some parts of the genome are resistant to change as they contain vital sequences - they are conserved
Describe how Mutation affects genetic variants
- Mutation is the process by which Variation in the genome arises
- We all carry large numbers of genomic variants and their frequency will depend on selection and when they first arose
- A rare variant may have risen recently or be deleterious and being selected against or both
Describe how Migration affects genetic variants
- Migration is the physical movement of people from a different population which results in new pools of variants being introduced to an existing population.
- This is called Admixture
- Population frequencies of specific variants can change purely due to admixture and not be disease related
Describe how Genetic Drift affects genetic variants
- This is how the frequency of a variant changes in a population due to chance
- Not all organisms in a population will pass on their genetic variants
- Mechanisms such as recombination will also result in not all variants being passed on
- All variants are subject to genetic drift
Describe Sequence Conservation
- DNA sequence conservation is vital to the survival of an organism. Doesn’t show much evidence of variation.
- Most variants in these regions will be selected against as they’re likely to have a strong deleterious effect.
- There is some flexibility for variation in the third base of codons as some amino acids are encoded by multiple codons.
What are the different types of Sequence conservation in genes?
- High conservation - Coding regions (not exons as these contain non coding regions)
- Intermediate conservation - promoter, 5’ UTR, 3’ UTR, terminator
- Low conservation - Introns, 3rd base of codons, terminator
What can Conservation be used for?
CROSS SPECIES COMPARISON
- Can be used to generate evolutionary profile for a gene or family
- Allows us to identify the important regions of a gene
- This allows us to concentrate on areas that appear to be important in novel genes
What is Phylogenetics?
Phylogenetics is the study of evolutionary relationships among biological entities
What is a phylogenetic tree? How can it be used?
- Has multiple diagram types
- Main aim is to illustrate the relatedness of different species or sequences
- Distance between two entities on a tree is usually related to how similar they are
- Distance is usually related to both evolutionary pressures and to time
- Time estimated by measuring mutation rates
How has Phylogenetics been used in the past?
- It had been theorised that HIV had been introduced to some of the human population via a contaminated polio vaccine in Africa
- Some polio vaccines used to be produced using cultured chimpanzee cells, which could have been infected with HIV
- Worobey eat al (2004) investigated this using phylogenetic
What is gene duplication?
The Duplication of the DNA sequence containing a gene
What is the typical mechanism for gene duplication?
The unequal crossing over during meiosis
What happens after gene duplication?
- One copy can continue the original function
- The other copy can evolve new functions through changes in the coding sequence and/or control sequences.
What is Unequal Crossing Over?
- Recombination between sequences that are not the correct sequence but are very similar
- Often low copy number repeat sequences
Describe the Globin genes
- Has 2 clusters
- Alpha-like are on chromosome 16 - 3 genes and 3 pseudogenes
- Beta-like are on chromosome 11 - 5 genes and 1 pseudogene
- The genes are arranged in order of expression during development
Describe the Alpha and Beta chromosome positioning???
Check over
Alpha: Haemoglobins in order of production during development
Beta: Symbols are Greek letters – Zeta, Epsilon, Alpha, Gamma, Delta and Beta
Green indicates DNA control elements
Describe the Globin Cluster Evolution
- Very clear that Globin genes have evolved through duplication and accumulation of mutations
- Some are functioning and some are not (Pseudogenes)
- Promoters have diverged so they bind to different transcription factors and allow expression of genes at different stages of development.
- Embryo -> Foetus -> Postnatal
What are Pseudogenes?
- After gene duplication, One gene can maintain the original function and the other can diverge
- Pseudogenes typically have many mutations and are non functional
- There are many of them in the genome
- They complicate PCR/sequencing
Sickle Cell Disease. When do the symptoms typically start?
Typically start at 5-6 months of age
What are the main symptoms of Sickle Cell Disease?
- Anaemia: Fatigue, Restlessness, Juandice
- Acute Pain Episodes: “Crises” x due to oxygen deprivation of tissues
- Increased frequency of infections: Spleen damage
What are the other symptoms of sickle cell disease?
Stroke, Pulmonary Hypertension, Gallstones, Liver and Kidney problems, Joint problems, Delayed Puberty
Explain the genetics of Sickle Cell Disease
- A single base change occurs in the beta Globin gene of Haemoglobin A = Haemoglobin S (HbS)
- Codon Changes from GAG to GTG
- This changes the amino acid from Glu -> Val at position 6 of the protein
- An autosomal recessive genetic disease
- The original mutation occurred 7300 years ago
Describe how Sickle Cell Disease is passed on through genetics
- If both parents have a copy of the HbS then each child has a 1 in 4 chance of having Sickle Cell Anaemia (2 copies of HbS)
- Sickle trait is common in African, Middle Eastern, Mediterranean and Indian populations and very rare in Northern Europe
Give an example of a heterozygote advantage
- 2ncopies of the HbS variant has significant negative effects on reproductive ability - SCD
- However one copy of the HbS variant confers resistance to severe Malaria
- This “heterozygote advantage” means that the HbS variant is maintained in the population when otherwise it would have been selected against and lost.
SUMMARY
- Mutational processes can lead to genes being duplicated
- They can also lead to new functions
- Evolutionary pressure can be very strong and lead to maintenance of apparently damaging variants
- Malaria and HbS are good examples of this
