11 Genomics I 23 with notes.pdf

11 Genomics I 23 Saturday, 30 December 2023 11 Genomics… 12:44 Exam is interpreta content This lecture i Ability to look at gen ation some calculations and some are recall from lecture is genomics place in genomics nome has had consequences for evolutionary biology Ability to look at ge...

11 Genomics I 23 Saturday, 30 December 2023 11 Genomics… 12:44 Exam is interpreta content This lecture i Ability to look at gen ation some calculations and some are recall from lecture is genomics place in genomics nome has had consequences for evolutionary biology Ability to look at gen There is obviously What is geno natural selec Then what c Genetic ba Genetic - sin Genomic - p telling from First part - wha Also lots of vari nome has had consequences for evolutionary biology y lots of diversity on this planet omic basis on variation and how is it shaped by ction? can it tell us about speciation asis of variation ngle genes, specifics patterns in whole genome, not actually specific, but paterns at is the genetic basis for phenotypic variation iation in a species or closely related species Also lots of vari E.g., stickleback different popula Or crow in engla A way to study the g the A QTL analysis Quantitative trait loc G.fortis - big beak G. scandens small be iation in a species or closely related species ks - they have boney plates, which varies amongst ation in same species. and is black and scottist crow ( same species ) are grey genetic basis for this is cus It is Limited in resolution And Works well when there are two forms of s a fertile cross of, e.g., between same species o species Identify genetic basis of traits There is a locus somewhere ( could be many ) that contribute to b size ( labelled with arrow at top ) eak If you cross these you get a F1 with one chromsone from each parent These individuals could be a half way house depending on man factors between two species species you can make or closely related beak h ny A genetic marker is a DNA sequence with a known physical location on a chromosome. Next generation F2 cros Can go through individu Prob big b large reso Some traits are com Monkey flowers M.lewisii - pink po M.cardinalis - red This is the F1 In F2 you get lo If you cross these you get a F1 with one chromsone from each parent These individuals could be a half way house depending on man factors between two species ss used, making thousands of F2 offspring ( F1 with F1 ) Make some form of genetic mark uals and score them for trait ( thick to small bill ) Can look at association between t Somewhere in genome the assoc genome which is responsible for v E.g., if you have blue part down at the bottom of gene ( bottom left ) it will be thick beak as this is where the locus responsible for variation is, on contrary bottom right where it is red will have thin beaks Middle indviduals are half way house Find association between the genet blem - in second generation there isn't much recombination - so normally just blocks of genome and not much segregation at correct places. There may be e chunks of DNA where it could affect a trait, so isn't specific. ( low olution ) mplex and interesting ollinated by moths d pollinated by hummingbirds ots of different phenotypes Same with butterflies ( on the righ h ny ker ( e.g., microsatellite ) trait and markers ciation will spike, ( getting close to part of variation ) e tic markers and beak size. ht ) This is the F1 In F2 you get lo QTL techniqu Stickleback These are de Different mo If you cross a c In F2 they are Tells you in all to map ) Crossed a plated ots of different phenotypes ue works best on simple mendelian trait F1 = F2 = provided a classical example ead stickleback which stained with red dye that sticks to bones orphs have different rows of plates from complete to half to short complete morph with low morph you always get F1 partial morph any of the three l probability it’s a single locus segregating with only 2 alleles ( good fish with a small low plated fish. = a mix of breeds = two F1's togetehr Crossed a plated They made F1 fam Used microsate Looked at asso Get a plot to se This one marke As there is Eda gene r have no sw Took eggs from Eda gene from m The transgenic f fish with a small low plated fish. mily and made F2's ellites ( genetic marker ) ociation at marker and compared if fish are fully plated or not ee association with marker and trait. er here is this most strongly associated with the trait s a gene which is well known( eda ) - responsible for outside of body traits e.g., humans who have mutant weat glands family of low plated fish ( two copies of eda gene ) and injected mice. fish some of them have plates ( bit at tail which is expected ) Apparently all lo All high plated st QTL experiment ow plated genes carry low plated allele and ticklebacks carry high plated allele This technique gives a This technique requir Can do genome scan - Closely related p - Genotype them from each other E.g., take broad and Sequence them and You can see in the at a locus And all pointy bea Exception of some a higher resolution - even though QTL is still used res no breeding. - which is hard in many species n population m ( look in places in genome where two species are different r) pointy beak finches see differences in genome ese species that in broad birds they all share a specific genotype aks share a specific locus in genotype e heterozygote birds You see all homoz All PP are pointy Hetroygous are be If you construct a Broad birds are c Pointy beaks are Genetic variation manner across sp E.g, in eda plated frequencies Can do sequence association again Great tits all zygous for BB are broad beaks etween a phylogeny for this gene clustered together clustered together n has been around for many years which gets used in a fluctuating pecies d fish even high plated fish will have the low plated at low es of individuals and look at association of character and genomic nst animals in its own species DNA collected Great tits all Looking at bill len At certain po Looked at DNA collected ngth variation oints in genome there are strong associations with beak length t gene called COL4A5 Looked if anima TT = short be CC = long bea Association b UK = CC and l Netherlands = This is due to als were homo or heterozygous for this gene generally eak ak between these genotypes and fitness long bills are more fit = TT short beak and allows higher fitness bird feeders in UK selecting for longer beaks This is due to Now what shape Three important - Selection - Gene flow - Recombina Classical studies of sel Here looking at coat In white sands - plac bird feeders in UK selecting for longer beaks es genomic variation? - understanding the forces to shape this processes ation lection t colour of mice ce in states where theres lots of sand - mice here are sand coloured Classical studies of sel Here looking at coat In white sands - plac Mice in country side Change occurs ove Looked at p When the Can look at select Looked at fish at look ponds They started the low this using the low alle And saw how they ro Different coloured lin They started to drop lection t colour of mice ce in states where theres lots of sand - mice here are sand coloured e are browner er short distances proportion of attacks ( by birds ) using artificially made mice and how they match sand ey are cryptic on their background they don’t get attacked so much tion on gene itself ked at frequencies of different EDA alleles of sticklebacks by puttig them in different alleles of EDA ( as they are polymorphic meaning multiple versions of same gene ele ) at 50% frequency ose dropped nes indicate different ponds used in the experiment then rose And saw how they ro Different coloured lin They started to drop Not sure why Seen as selec 21 fish sequenced from Tried for one marine an Compared these se ose dropped nes indicate different ponds used in the experiment then rose y advantageous - as it rises above 50% ction on gene itself in different pond habitats m different location nd one fresh water fish near each other equenced genomes from fresh water and marine These plots show a measur Big spike is where EDA EDA is main differenc Comparing closely rel Evolution - change in al Drift and directional sel re of divergence between genomes ( whole genomes ) A is. ce between fresh and marine stickleback lated populations and seeing genotype differences due to habitats difference llele frequency in generations - but can come about in two different way s lection Evolution - change in al Drift and directional sel Drift is ra Direction Dominant all After selection to fixatio Red allele on left is an all Genetic diversity before s If due to selection keep You get a population of Also likely to have other hasn’t had time to break llele frequency in generations - but can come about in two different way s lection andom and only really works in small populations nal is deterministic process leles if not favourable are removed quickest but if they are, are fixated quickest on - result in genome is called selective sweep. lele to turn butterfly red sweep at this locus is high ( many different alleles here ) ps red butterflies alive but kills other butterflies f red butterflies which all have red causal mutation r mutations closely linked to causal mutation to also be here as recombination k these associations A G L At location of sweep Genetic variation reduces Linkage disequilibrium increases You get a population of Also likely to have other hasn’t had time to break This part of genome is fa here. Due to red mutation bei But as recombination part of genome comp There are different type Classic hard sweep - Change in enviro - A mutation arise - Allele Swept to h Quite a rare thing now More evolution is Soft sweep Can be; - Describe situati - Can be multiple Normally; - Mutations that f red butterflies which all have red causal mutation A r mutations closely linked to causal mutation to also be here as recombination k these associations G L avoured in individuals and hence there is a massive reduction in genetic variation ing favoured by selection Linkage - tw Linkage dise hasn’t had time to break associations, there is a strong association of genes in this pared to others - called a high linkage disequilibrium. This causes problems in determining association alleles in the same sweep es of selective sweep onment changes pattern of selection ( e.g., red butterflies not being eaten ) es to be beneficial in new environment ( red butterflies now existing ) high frequency w ions that aren't hard sweep e different mutations to produce adaptive phenotypes become favoured, were segregating before selection started At location of sweep Genetic variation reduces Linkage disequilibrium increases wo genes are in physical proximity equilibrium - two genes which are statistically associated together g the causal mutation as there are now two strong p In soft sweep you get variation that exists in population, e.g., different set of mutations that are in different places in gene, which then get swept to high frequency May all be causing same phenotypic affect - however, they can be different - Describe situati - Can be multiple Normally; - Mutations that - Contributing to - These alleles be - When selection FsT = measure of diver Calculated amount of v population. Measure of divergen Done in 15-20 K In places where reduced variatio Can see in butte ions that aren't hard sweep e different mutations to produce adaptive phenotypes become favoured, were segregating before selection started standing variation eing maintained by in environment due to them being neutral n starts, these mutations are swept to high frequency rgence between populations variations that occurs in sub populations, relative to the amount in total nce between populations Kb chunks there's been selection there may be high Fst - as variation in certain allele will have on here, due to fixation of trait erfly species in heliconius species In soft sweep you get variation that exists in population, e.g., different set of mutations that are in different places in gene, which then get swept to high frequency May all be causing same phenotypic affect - however, they can be different mutations within the gene, but have different assoications with other loci. So easier to tell Can see in butte In gery band Fst but if you know erfly species in heliconius species goes high, it may be it’s a gene that’s to do with something else other than wing colour, what genes are you can see its due to variation reduction Gene flow process of v Gene flow is the variation e transfer of genetic material from one population to another. Gene flow is the Evidence comes from helico They all look simila Many species have Timareta and h.mama Contrasting expecte could occur Expect. H.m. amary But if timerata and e transfer of genetic material from one population to another. onius butterflies ar besides differences in wing colour e been exchanging genes through time aryllis share similar wing colour patterns phylogenic history against phylogenetic history of genes to see where gene flow yllis to share genes with other h.m butterflies d amarylsis are hybridising can see this Some genes are as expected but some places ha between timerata and amarlysis have been exch ave different topology which suggests hybridisation hanging genes But if timerata and Another example lon At some point there i Some genes are as expected but some places ha between timerata and amarlysis have been exch d amarylsis are hybridising can see this ng tail finches in australia have yellow to red beaks across australia is gene flow between finches ave different topology which suggests hybridisation hanging genes