Lecture 23 (Part 1) - Gene Loss Flashcards
What is the most common fate of duplicated genes?
Gene loss.
Give an example of major gene loss after a whole genome duplication event.
In baker’s yeast, only 8% of the duplicate genes (created by whole genome duplication) are still present in two copies.
Give an example of a species with a high rate of duplicate retention.
The African clawed frog (Xenopus laevis) - with more than 56% of its duplicate genes retained in two copies (despite their duplication event being 30 mya).
What are the two main mechanisms which lead to the loss of a gene from the genome?
- Abrupt mutational events (e.g., unequal crossing over, incorrect non-homologous end joining repair) leading to a sudden deletion of the gene from an organism’s genome.
- No evidence of the gene left (thus no evidence of its existence) - Nonfunctionalisation - an accumulation of loss-of-function mutations that eventually results in a non-processed pseudogene (i.e., a gene that no longer goes through any RNA processing).
- This is a slower process
- Still evidence of the gene left in the genome (in the form of this non-processed pseudogene)
What often follows a nonfunctionalisation event (i.e., what often happens to the pseudogene once it has become non-processed)?
Pseudogenisation is often followed by deletion (i.e., removal of the pseudogene sequence from the genome,
Does gene loss effect the fitness of an organism?
No, it is often a neutral mutational event (as there is a backup copy that can continue to carry out the gene’s function).
How can the process of nonfunctionalisation sometimes have deleterious effects?
Nonfunctionalisation is an accumulation of mutations (not just a single step), thus at the earlier stages of nonfunctionalisation the mutations might result in a truncated protein product which may be deleterious.
What is a unitary pseudogene?
Genes that are lost (nonfunctionalised) in the genome, but there are no paralogs (backup genes) to carry out the function.
- Almost always deleterious (because loss of a single copy gene means loss of a function)
- Rare, with 100 unitary pseudogenes in the human genome (compared to 20,000 pseudogenes with functional paralogs).
What are the two main mechanisms behind unitary pseudogenisation events?
- Use it or lose it hypothesis
- Where the function of the gene is no longer necessary for the organism’s fitness
- Thus, purifying selection will no longer conserve it - Less is more hypothesis
- Where the loss of the gene can be advantageous
- E.g., the loss of ancestral gene function may make a species better adapted to the environment
Give an example of a unitary pseudogene in humans (in relation to the use it or lose it hypothesis).
L-gulono-gamma-lactone oxidase gene.
- 7 out of 12 exons deleted in this gene in humans
- However, we do not see any fitness effect due to our Vitamin C-rich diet (similar deletions seen in monkeys, bats and guinea pigs)
- If human’s do not obtain Vitamin C in their diet, we are susceptible to scurvy
Give an example of gene loss due to dietary change (in relation to the use it or lose it hypothesis).
Tas1r2 (the gene for sweet taste perception) has been lost independently at least six times in the Carnivoran order.
Give an example of gene loss in humans (in relation to the less is more hypothesis).
Loss of MYH16 - leading to smaller jaw muscles. This may have been advantageous by…
- Increasing cranial capacity
- Allowing for speech
(But these are just hypotheses! This loss could also be a use it or lose it related to dietary change etc.)
Discuss the example of Caspase 12.
- Polymorphic in humans - functional and non-functional (pseudogenes) versions present
- The pseudogene is fixed (exists at 100%) in many populations
- Normally functions in inflammation and innate immunity
- However, can also sometimes lead to sepsis (body’s extreme response to infection, over-inflammaton)
- Loss of gene can result in prevention of sepsis (i.e., less is more!)
(Note! Two other genes involved in sepsis are also recent pseudogenes).
