GEN 4: Comparing Genomes

Question 1

Observe the learning outcomes of this session

Answer 1

Question 2

Observe the genomic variation across different species

Answer 2

Question 3

What does a higher degree of conservation mean for different species?

Answer 3

• the higher the degree of conservation, the more distant the species

Question 4

What does a conserved sequence mean?

Answer 4

• if there is a region in genomes of other species with the same or very similar sequence

Question 5

What is a sequence alignment?

Answer 5

• it is a match between two sequences

Question 6

Describe the types of sequence alignment

Answer 6

Question 7

What are three forms of sequence alignment?

Answer 7

• exact match
• some mismatches
• some gaps

Question 8

What makes for a well-aligned DNA sequence?

Answer 8

• more base matching
• fewer gaps
• smaller gaps
• fewer mismatches

Question 9

How do you use genomes browsers such as Ensembl?

Answer 9

Question 10

What are orthologs?

Answer 10

• these are the similar sequences on genomes of different species

Question 11

Do we actually share 50% of our DNA with bananas?

Answer 11

Question 12

How do we use the CLUSTAL omega tool to inspect the alignment of different genomes?

Answer 12

Question 13

What are examples of highly conserved genomic sequences?

Answer 13

• protein-coding sequences
• important regulatory regions (e.g. enhancers)

Question 14

How do you form a phylogenetic tree and how is it helpful?

Answer 14

• 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

Question 15

Look at the diagram and answer the two questions:

1. Which two organisms have the most similar MLH1 sequence?
2. Does MLH1 in D. melanogaster have the same origin as the human gene?

Answer 15

1. Human and Mouse
2. It looks as though the Drosophila sequence has diverged early on and has a different origin to mammals

Question 16

Why is genetic recombination during meiosis important?

Answer 16

• 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

Question 17

How does meiotic recombination generate genetic diversity?

Answer 17

Question 18

Where on the chromosome, on the microscopic level, does homologous recombination occur?

Answer 18

• within the branching points called chiasmata (sing. chiasma)

Question 19

What could go wrong during homologous recombination?

Answer 19

• 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)

Question 20

What happens when recombination occurs when a gene is flanked by two repeated sequences?

Answer 20

• chromosome misalignment may occur, resulting in gene deletion and duplication
• e.g. Charcot-Marie-Tooth disease (see e-module)
• this is called aberrant recombination

Question 21

What is a consequence of aberrant recombination that is a driving force in the evolution of complex organisms?

Answer 21

Question 22

Give an example of how gene families evolved due to aberrant recombination

Answer 22

• 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

Question 23

What are retrotransposons?

Answer 23

• a type of transposon which are transcribed to mRNA, then reverse-transcribed back to DNA and inserted back into the genome

Question 24

What are endogenous retroviruses?

Answer 24

• 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

Question 25

What is selection pressure?

Use bacteria growing in a dish as an example

Answer 25

• 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

Question 26

When the DNA sequence of a gene is identical across many different species, what does this suggest about the importance of that sequence?

Answer 26

• 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

Question 27

What is a Single Nucleotide Polymorphism (SNP)?

Answer 27

• it is a single position in the genome that is polymorphic (is observed with different nucleotides) in at least some of the population

Question 28

How can comparing genomic features improve cancer diagnostics?

Answer 28

Question 29

How can comparing genomic features improve AIDs treatment?

Answer 29

• 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.

Question 30

How can comparing genomic features improve managing genetic disease risk?

Answer 30

Question 31

How can comparing genomic features improve in monitoring disease outbreaks?

Answer 31

Question 32

How can comparing genomic features improve in choosing the correct treatment?

Answer 32

• 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.