Evolution of Vertebrate Signalling Flashcards
What is the human 14-3-3 interactome enriched in?
2R-ohnologues
What is the best extant proxy of our extinct invertebrate ancestor?
Amphioxus
What is an invertebrate?
It has no bones, heart, paired limb, or sensory eyes but does have a sensory patch
How did the genome of our ancestors develop into ours?
The chromosomes undergo major losses to make them different lengths and then through mutations, rearrangements and diploidisation we developed our chromosomes
What are ohnologues?
A group of paralogues which are generated by whole genome duplication events
What is synteny?
Where the gene content of the true chromosomal locations are similar
Give examples of ohnologues in the human genome
Ras - N-, K-, R- and H-
Raf - A-, B- and C-
How many protein kinases belong to 14-3-3 binding 2R protein families?
66% of the kinome
391
What is 2R-WGD?
Two rounds of whole genome duplication (1R and 2R) occured early in the evolution of vertebrates - producing 4 copies
What happened to the quadrupled genes after 2R-WGD?
One to three of the four gene copies in most cases were lost
only ~25% of the human genome comprises of families of between 2-4 ohnologues
What is the lynchpin hypothesis?
That there is one conserved phosphosite (lynchpin) and one which is very different across all family members (evolutionary site) but both bind 14-3-3
The lynchpin site gives freedom for the other site to evolve
How has the discovery of lynchpins and evolutionary sites affected 14-3-3 research?
It allows bioinformatic predictions for 14-3-3 binding sites
Allows you to know if the 14-3-3 induces a masking effect, ordered effect or changes the interactions between the domains
since ohnologues are similar, why are they not all bound to 14-3-3 at the same time?
Didn’t stimuli induce different binding
What percentage of somatic mutations in cancer are in 2R-ohnologue genes?
42-60%
What are driver mutations?
Provide a net growth advantage and are under positive selection during tumourigenesis
