GEN 4: Comparing Genomes Flashcards
Observe the learning outcomes of this session
Observe the genomic variation across different species
What does a higher degree of conservation mean for different species?
- the higher the degree of conservation, the more distant the species
What does a conserved sequence mean?
- if there is a region in genomes of other species with the same or very similar sequence
What is a sequence alignment?
- it is a match between two sequences
Describe the types of sequence alignment
What are three forms of sequence alignment?
- exact match
- some mismatches
- some gaps
What makes for a well-aligned DNA sequence?
- more base matching
- fewer gaps
- smaller gaps
- fewer mismatches
How do you use genomes browsers such as Ensembl?
What are orthologs?
- these are the similar sequences on genomes of different species
Do we actually share 50% of our DNA with bananas?
How do we use the CLUSTAL omega tool to inspect the alignment of different genomes?
What are examples of highly conserved genomic sequences?
- protein-coding sequences
- important regulatory regions (e.g. enhancers)
How do you form a phylogenetic tree and how is it helpful?
- in Clustal, there is a ‘Phylogenetic Tree’ tab
- this produces a diagram that represents how related sequences are and gives us an idea of when species branched off from each other during evolution
Look at the diagram and answer the two questions:
- Which two organisms have the most similar MLH1 sequence?
- Does MLH1 in D. melanogaster have the same origin as the human gene?
- Human and Mouse
- It looks as though the Drosophila sequence has diverged early on and has a different origin to mammals
Why is genetic recombination during meiosis important?
- because both of the parental chromosomes came from organisms that were able to survive to reproductive age
- any change during meiosis is unlikely to be deleterious
- because recombination occurs during meiosis, each of the germ cells that will pass genetic information to subsequent generations will contain a mixture of the DNA from the two parents
- by exchanging information between the parental chromosomes, genetic diversity is maintained without the risks associated with random mutation
How does meiotic recombination generate genetic diversity?
Where on the chromosome, on the microscopic level, does homologous recombination occur?
- within the branching points called chiasmata (sing. chiasma)
What could go wrong during homologous recombination?
- there could be segregation errors
- both copies of a chromosome end up segregating into the same cell
- resulting in one of the zygotes having an extra copy of the chromosome, and one lacking that chromosome
- if they are fertilised and form embryos and they have
- wrong number of chromosomes: aneuploidy
- one copy of a chromosome: monosomy
- three copies: trisomy (e.g Down’s)
What happens when recombination occurs when a gene is flanked by two repeated sequences?
- chromosome misalignment may occur, resulting in gene deletion and duplication
- e.g. Charcot-Marie-Tooth disease (see e-module)
- this is called aberrant recombination
What is a consequence of aberrant recombination that is a driving force in the evolution of complex organisms?
Give an example of how gene families evolved due to aberrant recombination
- if there is a selective advantage in having multiple specialised versions of a given protein
- e.g. for globin gene family: with two sub-families of alpha-globin and beta-globin
What are retrotransposons?
- a type of transposon which are transcribed to mRNA, then reverse-transcribed back to DNA and inserted back into the genome
What are endogenous retroviruses?
- a type of retrotransposon
- makes up approx 8% of the human genome
- it is believed that these were once viruses that had infected humans, but their pathogenic effects were lost
- over time, these sequences can mutate and move around the genome, sometimes evolving into functional regulatory elements e.g. enhancers
What is selection pressure?
Use bacteria growing in a dish as an example
- bacteria are growing in a dish
- they divide
- the DNA in some bacteria mutates
- DNA sequence changes can affect growth rate
- over time, bacteria with the sequence tat gives fastest growth will dominate the population
- the sequence has been selected through its proliferative advantage
When the DNA sequence of a gene is identical across many different species, what does this suggest about the importance of that sequence?
- the sequence is important for function
- during evolution, there are countless opportunities for individuals to develop changes in their DNA sequence
- if it does not change, we know there must be a strong selection pressure to maintain that sequence
What is a Single Nucleotide Polymorphism (SNP)?
- it is a single position in the genome that is polymorphic (is observed with different nucleotides) in at least some of the population
How can comparing genomic features improve cancer diagnostics?
How can comparing genomic features improve AIDs treatment?
- The HIV virus comes in many forms with different genome sequences. By tailoring the anti-retroviral drugs a patient receives to the sequence(s) of their virus, outcomes have been dramatically improved over the past 20 years.
How can comparing genomic features improve managing genetic disease risk?
How can comparing genomic features improve in monitoring disease outbreaks?
How can comparing genomic features improve in choosing the correct treatment?
- all drugs used in the treatment of disease are metabolised in the body
- For some this is required to activate them and nearly all are metabolised which inactivates them and/or helps remove them from the body
- Drugs most commonly target either receptors or enzymes.
- All of these stages can be affected by genetic variability within patients. Sometimes this is relativly minor causing minor side effects or changes the dose need. Other times it can be life threatening. This is known as PHARMACOGENOMICS now an increasingly important consideration in treating patients.
