BG23 Flashcards
Mapping adaptive traits
if an adaptive trait is polymorphic withn interbreeding population it can be mapped
- if genetic basis is complex, QTL analysis must be used to map it
QTL mapping steps
step 1: physical map of polymorphic markers (SNPs etc) can be used.
step 2: make recombinant inbred lines. - easy to make in c. elegans as faultively selfing hermaphrodite
step 3: phenotype RILs
step 4: genotype RILs
step 5: search for association between them
results of QTL mapping in c. elegans
bristol and bergerac strains differ in body size and fertility
found that RILS differ in body size and fertility
- several QTLs are identified for each trait
- only the causal region, not the mutation itself is identified.
Dog correlations with body size
10K since divergence from wolves
- selected for body size
- also differ in IGF blood titre (causally)
Portugese water dog mapping
genetic map constructed using SNPs
- body size (which is variable in PWD) was mapped
results of portugese water dog mapping
single qtl found on ch.15 near igf-1 locus
- marker variation around this locus can be reduced two two haplotypes which directly predict size and igf titre level
- clear variant in region influences both
scoring of frequency of ch.15 igf-1 haplotype in different breeds
when scored in different breeds in predicts body size based on IGF
(except in rottweilers)
IGF- 1 locus in dogs
selection
subject to selective sweep
elevated fst around igf locus
locus is more different among breeds than flanking region
Peppered moth forms
and species
B. betlulariac
typica - peppered
carbonaria - melanistic
carbonaria locus
mapped to ch17
encodes gene called cortex
carbonaria allele contains a tandemly repeated transriptional element
drosophila homolog of cortex
cell cyle gene
cortex expression in moths
expressed in splice variants
- differentially expressed in wing imaginal disk
some (CR4) are differentially epxressed between typical and carbonaria genotypes
- transposable elements regulate expression of cortex - or atleast some of its mRNA variants at particular times
Carbonaria synteny
pigment patterning loci in other butterflies bigeye and bicyclus and N-P-Yb-Cr/P mimicry locus in Heliconus all map to chromosomal regions syntenic with carbonaria
stickleback fresh water invasion
usualyl marine
invaded freshwater >20 times indep.
when they do so they tend to lose the pelvic spines and girdle and armous plating - lack of predation? or lack of Ca?
stickleback pelvic bone loss qtl
largest is on ch7
- around TF pitx1 which is known to be important in skeletal formation
Sequencing and expression patterns between marine and fresh water sticklebacks of pitx1
- no difference in coding regions between marine and freshwater morphs
- difference in expression pattern.
marine and freshwater stickleback cross
compared allele specific expression of pitx1 using qtPCR
- marine allele has higher lvels of expression so the different must be due to cis-acting reg elements
sequencing of pitx1 reg region
freshwater strains msising 501 bp region upstream of pitx1.
- potentially contains causal reg element
how did they show that the cis acting reg element drives expression in the pelvis
take the saltwater sequence of 2.5kn region deleted in freshwater fish adn put it behind a GFP reporter and transfect the fish.
- see it drives expression in pelvis
how can it be shownt that Pel-2.5kbSALR contains the causal mutation
put it behind a freshwater pitx1 coding region
- transfect the freshwater fish
- rescues pelvic spine phenotype = prove
Pel loss around the world
sequencing shows always lost, lost indep since the precise deletion varies
= convergence at a molecular level.
how do we know that loss of pel enhancer is adaptive?
- repeated loss
- signature of selection: loss of heterozgyosity around pel implying a selective sweep.
how can we find out if pel is responsible for loss of pelvic structures in two differnet species of stickleback
- complementation test
- F1 hybrid,
if alelles fail to complement the same locus (pel-pitx1) must be responsible for loss of pelvic structures in freshwater morphs of both species.
Lizard pigmentation in white sands of new mexico
independent evolution of pale morphs
due to different mcr-1 mutationswhich regualtes switch between phaeomelanin and eumelanin production which is involved in pigmentation polymorphisms,
how can we test the ability of mc1-r mutations of the mexican lizards to transduce a signal
by engineering them in mamamlian cells and challengint them with a ligand and notin the function
- found loss of function
what are the 6 steps for identifying adaptive genes
- examine candidate genes for phenotype
- if no candidates doa QTL (markers, constructs, physical map, crosses)
- sequnce QTL region for possible mutation (if find NS coding mutation could be this, if not cis acting).
- do functional studies - expression studies, in vivo assays, KOs etc to make case for causal roles of a locus
- examine sequence around putative causal locus for signatures of selection
- gold standard of proof for causal involvement of locus is phenotype is to rescue by transgenesis or complementation.
why might CREs be more important in adaptation
- effects of cre mutations can be more specific that those of coding mutations and are likely to have fewer pleiotropipc effects (more modular), e.g. cre of shh can cause polydactyly or limb loss but null = lethal
NS coding mutations are the most known adaptive aleles?
- some studies have shown this
- however there is a bias as coding mutations in general are easier to find
is evolution predictable
- no. of cases where indep mutations have occured in the same genes pitx1, mcr1
- other cases ancient mutations are re-used
why may the same mutations crop up
many mutations have small phenotypic effects, few have strong ones
when selection is strong those with the largest phenotypic effects will be picked out first
even though they’re the most likely to be deleterious.
when might we expect to see complex traits
when selection is weaker may expect many genes will be involved giving rise to adaptive traits controlled by many loci; complex traits
