molecular evolution Flashcards
Natural selection
The effects of a wide range of factors on the frequency of heritable changes in a species
Fitness
How well a species is able to reproduce in its environment
The link between evolution and genetics
Evolution with genetics can help explain the molecular process underlying evolution.
Frequencies of genetic variants are affected by
Selection, Mutation, migration, genetic drift
Selection
Genetic variants that confer a positive advantage will be selected for (vice versa)
Example of selection
Confer resistance to disease, an ability to metabolise a new food source, antibiotic resistance or a change in appearance that enhances mate choice
Anomalies with selection
• Some parts of the genome are resistant to change as they contain vital sequences – they are conserved
Mutation
- The name for the process by which variation in the genome arises is mutation
- 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 arisen very recently or be deleterious and being selected against or both
Migration
- The physical movement of people from a different population 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.
Genetic drift
- 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
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 a strongly deleterious effect
- There is some flexibility for variation in the third base of codons as some amino acids are encoded by multiple codons
High conservation
coding regions (not exons as these contain non-coding regions)
Intermediate conservation
Promoter, 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 can be used to 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)
- This allows us to concentrate on areas that appear to be important in novel genes
Main phylogenetic trees
- Main aim is to illustrate the relatedness of different species/strains/sequences
- Distance between two entities on a tree is usually related to how similar they are
- Distance is normally releated to both evolutionary pressures and to time
- Time estimated y measuring mutation rates
Infectious disease and phylogenetics
- 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 SIV
HIV and polio vaccine
- The tree demonstrates that the SIV genome in DRC wild chimpanzees was completely distinct from all HIV genomes
- Other SIV strains were likely to be the source as they are closely related to HIV
What is gene duplication?
- This is duplication of a DNA sequence containing a gene
* 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 function(s) through changes in the coding sequence and/or control sequences
Unequal crossing over
- Recombination between sequences that are not the correct sequence but are very similar
- Often low copy number repeat sequences
Globin genes
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.
What are the greek letters
Zeta, Epsilon, Alpha, Gamma, Delta and Beta
Globin gene expression
Hb F (fetal) - high alpha, high gamma. Early on, high epsilon and zeta
Hb A (after birth) - alpha, beta, low gamma, low delta
Globin cluster evolution
- Very clear that globin genes have evolved though duplication and accumulation of mutations (divergence)
- Some are functioning genes and some are not (pseudogenes)
- Divergence of promoters has occurred so they bind different transcription factors and allow expression of genes at different stages of development (Embryo->Foetus->Postnatal)
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/etc!
Sickle cell disease symptoms
Symptoms typically start 5-6 months of age
• Anaemia – fatigue, restlessness, jaundice
• Acute pain episodes – “crises” – due to oxygen deprivation of tissues
• Increased frequency of infections – spleen damage
• Also stroke, pulmonary hypertension, gallstones, liver and kidney problems, joint problems, delayed puberty
Codon change for Sickle cell gene
GAG - GTG
Glu > Val at position 7 of the protein
What type of genetic disease is sickle cell disease?
Autosomal recessive genetic disease
When was the original mutation for sickle cell disease
7300 years
Where is sickle cell common?
African, middle eastern, Mediterranean and Indian populations and very rare in northern Europe
Why is sickle cell common in these areas?
- Two copies 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.
