Population Structure, Selection, and Drift handout Flashcards
what doesn’t change under hardy-weinberg equilibrium
neither genotype frequencies nor allele freqneices
adaptation
caused by changes in allele frequencies so have to relax one or more hardy Weinberg assumptions
genetic drift
if population size is finite then by chance certain alleles will be over or under represented in each generation (variation in relative frequency of diff genotypes im small population); don’t know beforehand which alleles go up or down in frequency (doesn’t matter if beneficial or not)
selection
positively selected (beneficial alleles) increase in frequency; non-random change in frequency of genetic variant due to differential fitness
genetic drift always leads to
loss of genetic variation once allele is lost form population because it can’t drift back into existance
mechanisms for regaining lost genetic varriation
mutation or migration
genetic drift is high when
effective population size is small
effective population size
population of individuals randomly mating
mutation
process by which variants are created for selection to act upon
mutation rate
u; is quite small; however genome is quite large (every persons germline has about 60 new mutations; every position in genome v likely to get mutated in every generation of humans (not individual human but all of the humans with all of the genomes at least 1 mutation likely to pop up for each location)
types of mutations
neutral, deleterious, beneficial
neutral mutations
most mutations are unelected or neutral
deleterious mutations
selected upon because they affect phenotype, alter a protein structure or alter its expression; these are more common than beneficial mutations (because living in environment and adapted to it so less chance of something making you more adapted than less); selection acts to remove these from population
benfieicial mutations
selected upon because they affect phenotype, alter protein structure, or alter its expression; these are least common type of mutation;
fitness
defined as number of offspring an individual has surviving to maturity
selection coefficient
s; to determine s normalize the fitness of background population to 1; this = the strength of selection acting on a mutation
fitness of homozygous mutant
1 + 2s
fitness of heterozygous mutant depends on
dominance (h); is 1 + 2h x s
h= 0 for recessive
h= 1 for dominant
h= 0.5 for additive variants
beneficial variants s
- beneficial variants have s>0
- deleterious mutations have s<0
- neutral mutants have s=0
three types of selection
stabilizing, directional, diversifying
stabilizing selection
organisms well adapted to environment don’t want to be too big or too small ect so select against things on outside of curve and things get pushed toward middle
directoinal selection
push population toward new mean of whatever is beneficial (ie if good to be tall get pushed toward tall)
diversifying selection
sometimes middle isn’t good things on low end and high end good so loose the middle if they are genetically separated end up with two new populations or new species
natural selection
survival of the fittest totaly blind, sexual selection is under this (sexual selection is on traits that effect mating success can be detrimental to survival); acts on anything that effects survivorship or fecundity in particular environment
artificial selection
caused by human directed breeding for certain traits some of which would be onfterhise disfavorable ex. hairlessness in Chinese crested which is embryonically lethal when homozygous
natural vs artificial selection in dogs
natural in wolves then to village dogs with some mix of natural and artiificaul than transitional breeds with more articiaul then to register breeds which are almost all aritificial other than needing to be able to survive
selection acts upon
phenotype
most mutations have no effect on
an organisms phenotype and even those that do have no discernible effect on fitness (these are neutral mutations)
selection is strongest
large populations; the opposite is true for drift
positive selection
once beneficial mutations reach an appreciable frequency they keep rising in frequency via positive selection until they become fixed
in small populations drift leads to
fixation of large number of neutral or even somewhat deleterious variants in large populations it is the mutations that are selectively advantageous that get fixed
calculating s 10% fitnes reductoin
s= - .01
s is usually v close to 0 if it is close enough to zero acts like a nearly neutral variant
larger populations selection is stronger because
smaller range of selection coefficients around zero that behave neutrally
drift acts on ____ loci in the genome, selection acts on ___ loci
all, specific
genetic hitchhiking
chromosomes are inherited in chunks positively selected alleles carry w/e haplotype it is on to high frequency along with it bc linked variants
dog body size selection since domestication
- Directional selection for smaller body size and/ or relaxation of selection as adaptation to scavenging
- Diversify selection for size during breed formation, followed by stabilizing selection for size within most breeds
melanistic wolves
black coloration in wolves due to mutation also found in dog breeds (was introduced from dogs into wolves by hybridization) some populations of wolves selected for black coloration now
fate of new mutations
depends on selection, effective population size, and drift
- selection dominates drift when s and Ne are large enough
- even strongly selected mutations are likely to be lost by chance when rare
newly arising neutral mutations equations
newly arising neutral mutations probability of reaching fixation: p=1/(2Ne)
fixation: p=1
Takes an average of 4Ne generations to reach fixation
- beneficial mutations reach fixation with probaliyt 2hxs (quicker than neutral mutations)
when you have beneficial mutation its chance of fixing
is same as its selection coefficient
N=Ne
census population size = effective population size if pop size stable/ fixed and mating is random
fluctuating population size
reduces Ne
sex ratio distortion and non-random mating
reduce Ne (population sire effect)
Wahlund effect
Deficit of heterozygotes (have two populations that aren’t exchange heterozygotes); model heterozygote deficit due to population structure as Fst
Fst equations
AA p^2 + Fstpq
Aa 2pa(1-Fst)
aa q^2 + Fstpq
Fst
measures decrease in heterozygosity bc of differences in allele frequencies btwn subpopulations vs total population; Fst= measure genetic differentiation btwn groups; higher if groups undergo a lot go genetic drift lower if migration occurs btwn the groups
selection size is stronger in population with
larger effective sizes
additive vs dominant vs recessive selection
strongest on additive because every addition makes improvement (if good)
- on dominant mutation selection inefficient because rise quickly but then plateus bc won’t matter if heterozygous or homozygous so won’t weed out heterozygotes
- recessive takes forver to gain selection acting on it strongly but once has foothold have dramatic selection on it
selective sweep
acts to fix not only selected allele but also other variants on that haplotype; positively selected variant that reaches high frequency (or fixation) quickly drags along linked variants (via genetic hitchhiking or genetic drift) reducing diversity and heterozygosity in that region; recombination will lead to some variation but not much
size of selective sweep footpring
depends on speed of sweep (deepening on strength of selection driving sweep); faster sweep means less genetic diversity because less time for recombination to act on it; once fixed recombinant can’t do much before recombining identical chromosomes; partial sweep occurs when sweep still in progress or where it has stalled
IGF1 dogs
selective sweep for small body size; fixed for small dog IGF1 allele; significant association with missense mutation on IGF1R on chromosome 3; <1Mb away mutation on splice donor site of ADAMTS17 is cause primary lens lunation in terriers -> more lens lunation in terriers
short legged dogs
have little genetic diversity because we selected for the short legs and weeded a lot of diversity out breeding these linked traits in
extreem Fst outliers
signal of recent adaptation; extreme Fst outlier in dogs is the one for floppy ears bc it is most strongly selected for thing because dog breeds have their own standard ear conformation
dog wolf selection sweeps
referred to as domestication sweeps; there are 36 genomic regions with selective sweeps in dogs vs wolves
- brain genes
- regions containing genes relating to strach/ fat metabolism
- region contained egg/ sperm; binding/ recognition proteins
if selection is so efficient at weeding out bad mutations and fixing good ones why do we still have genetic dx
- hitchhiking
- pleiotropy
- drift
hitchiking
deleterious mutations hat would be lost by selection rise in frequency via hitchhiking if linked to positively selected traits
Dalmatian stones
linked to spots so select for spots select to be prone to stones
pleiotroy
variants can have multiple phenotyic events or even different events in different environments
- ex thrifty genes good during famine but make you fat during norma life
- large size selected for in some dog breeds but -> cancer and shorter lifespan
- copy # increase in HAS2 promoter leads to increased wrangling but predisposes dogs to familial Shar Pei fever
drift
small Ne leads to strong drift, all but most strongly deleterious mutations may by chance rise to high frequency in small populations
- rare variants can be moderate deleterious to fitness bc tend to be recent mutation and selector hasn’t had time to weed out yet (rare deleterious recessive mutations v hard to weed out)
- common variants may underlie genetic dx but usually these have little or no fitness effect (either late onset or each variant may account for small portion of dx risk)
epistasis
selected variants often interact with each other (copy number variant leads to squamous cell carcinoma in digit in black but not white poodles
predicatble
selection in some sense predictable; mutations in same genes and gene pathways found across species when selection acting on similar traits (animals great models for human genetic dx)
gene x environment interactions
genetic variants may respond differently to different environments
selection on rare recessive variants
selection is very inefficient since these variants are v seldom homozygous and thus seldom have phenotypic effect
