BG3 Flashcards
gene no. association with complexity
rough association between metazoans and unicells
humans 25000, e.coli = 4000
however relationship breaks down in metazoans
c. elegans = 19000
amphioxous = 21,900
orthologues
gene or proteins in different species that are more closely related to each other than genes present in those species
example: six3/6 and optix
paralogues
genes or proteins within a single species that are closely related to each other
example: six3 and six6
what are 4 main mechanisms of genome evolution
- gene duplication
- polyploidisation
- exon and domain shuffling.
- non-coding regulatory element
5, gene loss
susumu ohno 1970 hypothesis
gene no. could increase by duplication or polyploid
how does gene duplication occur
unequal crossing over
chromatid pairs align incorrectly so that after crosing over, one chromatid will have two copies ad other will lack *usually lethal.
- one gene tends to conserve ancestral function
gene duplication in humans
resequencing shows most genes seem to be diploid
but high vairation in copy no. in humans
implies gene duplication is continuous and common.
what are many of the genes duplicated in humans compared to other apes
involved in brain development
GPRIN2 and SRGAP2 - implicated in neurite outgrowth and branching.
HYDIN2: associated with micro and macrocephaly.
DRD-5 dopamine receptor.
gene duplication among ethnic groups
as many as 2/10/11 gene duplications.
Polyploidy leading to vertebrates
seems to be two rounds of whole genome duplication leading to vertebrates.
- first in branch from amphioxous to tunicates
- second in the branch diverging from jawless fish (hagfish)
what is synteny
- why may is not be the case
conservation of large scale genomic architecture.
- gene function is independent of gene location so shuffling can break up synteny, however this is sufficiently slow for synteny to occur generallly.
describe the synteny of amphioxous and higher vertebrates
basic structure sufficiently conserved that can be aligned with genome of higher vertebrates.
- amphioxous genome shows large regions where genes correspond more or less ot those of particualr human chromosomes.
what is the direct evidence of vertebrate polyploidsation
amphioxous genome can be reduced to 17 linkage chromosomes (ancestral linkage groups)
these are found to be distributed across the vertebrate genome.
in general in any given component there are usually four different places where it has been distributed across vertebrate genome, usually adds up to no more than 4 of those genes.
suggests two whole genome duplication
implication of duplication on genome size of amphioxous compared to humans
would expect 4x as many genes in humans
however, humans = 25,000, amphioxous = 20,000
suggests widespread polyploidisation followed by mass reduction.
what is exon shuffling
exons from two or more differnet genes can be brought together ectopically or the same exon can be duplicated.
- important common mechanism by which new classes of proteins are made.
- an exon contains a no. of functional domains
what is domain shuffling
gene segment coding for functional domains are shuffled between different genes during evolution
- boundaries between domains may or may not correspond to exon boundaries, occasioanlly a single domain is encoded by more than one exon.
what causes domain and exon shuffling
unequal crossing over within introns can cause new domains to be added or lost or new exons to be put together
how do vertebrate domains compare to other metazoans
have few new domains but many proteins with more complex combos of domains
what is gene regulation often accomplished by, how can these evolve
cis acting reg elements. - can be duplicated and diverged to acquire more complex functions
Give an example of importance of cis acting regulatory elements
drosophila - initial embryo is a syncytia.
concentration gradients of TFs cause different levels of gene expression.
each stripe on drosophila is determined by precide levels of TF binding to particualr cis acting reg element.
how is second stripe of dorophila formed
cis acting reg for second stripe is bound by repressors such as Giant, kruppel and activators such as bicoid and hunchback in different regions at precise levels
evo history of non coding reg elements in vertebrates
the reg regions of genes involved in post translational modification have become more complex late in vertebrate evolution
** suggests how we can get away with fewer genes: more post translation reg,
those of transcription factors became complex early
yeast mating
fusion of partner cells stimulated by pheromones
responses mediated by signalling moelcules heterotimeric G protein ste2 and mitogen activated protein MAP kinase cascades
describe experiment of genome evolution
constructs with duplicated genes, duplicated domains and co-expressed domains and new combos of domain (domain shuffling) were made and put back into yeast.
matting efficieny was assayed and recombinate relative to WT.
results of experiment of genome evolution
gene duplication, domain duplication and domain co-expression had little effect.
some duplicated domain constructs were less efficient.
but making proteins with new combos of domains changed mating efficiency greatly - in some cases increased (may not occur naturally due to pleiotropy)
domain shuffling can therefore bring about major phenotypic effects.
explains freq in evo
gene loss in vertebares
with polyploid expect humans to have 80,000 genes.
vertebrate gene loss
Gene loss in platypus,
monotremes lay eggs, plesiomorph share with amphibians, reptiles and birds.
monotremes like these^ have yolk proteins vitellogenins
marsupials have 1
eutherian mammals have none.
describe vitellogenin evolution in vertebrates
`1. duplication of yolk proteins leading to amphibians who lay gelatinous eggs (x2 vtgA/B), X2 vtgA1/A2
- monotremes have lost VIT1 but maintained VIT.
- VIT2 extinction in eutherians.
- inactivating mutations in vitellogenin genes in platypis and opposum can be seen, stop codons and indels.
Bdelloid rotifer genome evolution
- polyploidy
- gene duplication, alpah tubulin (antarctic fish), lea-1.
- gene conversion - mutation accumulation deal.
- HGT, 10%
exon shuffling in defensins
arhtopods and molluscs compared to scorpian defensin
found aside from exon encoding mature protein differ widely in no., size and seq.
variability suggests exon encoding mature defensin has undegone exon shuffling and integrated downstream of unrelated leader seq.
