Population Structure, Selection, and Drift handout

Question 1

what doesn’t change under hardy-weinberg equilibrium

Answer 1

neither genotype frequencies nor allele freqneices

Question 2

adaptation

Answer 2

caused by changes in allele frequencies so have to relax one or more hardy Weinberg assumptions

Question 3

genetic drift

Answer 3

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)

Question 4

selection

Answer 4

positively selected (beneficial alleles) increase in frequency; non-random change in frequency of genetic variant due to differential fitness

Question 5

genetic drift always leads to

Answer 5

loss of genetic variation once allele is lost form population because it can’t drift back into existance

Question 6

mechanisms for regaining lost genetic varriation

Answer 6

mutation or migration

Question 7

genetic drift is high when

Answer 7

effective population size is small

Question 8

effective population size

Answer 8

population of individuals randomly mating

Question 9

mutation

Answer 9

process by which variants are created for selection to act upon

Question 10

mutation rate

Answer 10

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)

Question 11

types of mutations

Answer 11

neutral, deleterious, beneficial

Question 12

neutral mutations

Answer 12

most mutations are unelected or neutral

Question 13

deleterious mutations

Answer 13

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

Question 14

benfieicial mutations

Answer 14

selected upon because they affect phenotype, alter protein structure, or alter its expression; these are least common type of mutation;

Question 15

fitness

Answer 15

defined as number of offspring an individual has surviving to maturity

Question 16

selection coefficient

Answer 16

s; to determine s normalize the fitness of background population to 1; this = the strength of selection acting on a mutation

Question 17

fitness of homozygous mutant

Answer 17

1 + 2s

Question 18

fitness of heterozygous mutant depends on

Answer 18

dominance (h); is 1 + 2h x s
h= 0 for recessive
h= 1 for dominant
h= 0.5 for additive variants

Question 19

beneficial variants s

Answer 19

• beneficial variants have s>0
• deleterious mutations have s<0
• neutral mutants have s=0

Question 20

three types of selection

Answer 20

stabilizing, directional, diversifying

Question 21

stabilizing selection

Answer 21

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

Question 22

directoinal selection

Answer 22

push population toward new mean of whatever is beneficial (ie if good to be tall get pushed toward tall)

Question 23

diversifying selection

Answer 23

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

Question 24

natural selection

Answer 24

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

Question 25

artificial selection

Answer 25

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

Question 26

natural vs artificial selection in dogs

Answer 26

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

Question 27

selection acts upon

Answer 27

phenotype

Question 28

most mutations have no effect on

Answer 28

an organisms phenotype and even those that do have no discernible effect on fitness (these are neutral mutations)

Question 29

selection is strongest

Answer 29

large populations; the opposite is true for drift

Question 30

positive selection

Answer 30

once beneficial mutations reach an appreciable frequency they keep rising in frequency via positive selection until they become fixed

Question 31

in small populations drift leads to

Answer 31

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

Question 32

calculating s 10% fitnes reductoin

Answer 32

s= - .01

s is usually v close to 0 if it is close enough to zero acts like a nearly neutral variant

Question 33

larger populations selection is stronger because

Answer 33

smaller range of selection coefficients around zero that behave neutrally

Question 34

drift acts on ____ loci in the genome, selection acts on ___ loci

Answer 34

all, specific

Question 35

genetic hitchhiking

Answer 35

chromosomes are inherited in chunks positively selected alleles carry w/e haplotype it is on to high frequency along with it bc linked variants

Question 36

dog body size selection since domestication

Answer 36

1. Directional selection for smaller body size and/ or relaxation of selection as adaptation to scavenging
2. Diversify selection for size during breed formation, followed by stabilizing selection for size within most breeds

Question 37

melanistic wolves

Answer 37

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

Question 38

fate of new mutations

Answer 38

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

Question 39

newly arising neutral mutations equations

Answer 39

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)

Question 40

when you have beneficial mutation its chance of fixing

Answer 40

is same as its selection coefficient

Question 41

N=Ne

Answer 41

census population size = effective population size if pop size stable/ fixed and mating is random

Question 42

fluctuating population size

Answer 42

reduces Ne

Question 43

sex ratio distortion and non-random mating

Answer 43

reduce Ne (population sire effect)

Question 44

Wahlund effect

Answer 44

Deficit of heterozygotes (have two populations that aren’t exchange heterozygotes); model heterozygote deficit due to population structure as Fst

Question 45

Fst equations

Answer 45

AA p^2 + Fstpq
Aa 2pa(1-Fst)
aa q^2 + Fstpq

Question 46

Fst

Answer 46

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

Question 47

selection size is stronger in population with

Answer 47

larger effective sizes

Question 48

additive vs dominant vs recessive selection

Answer 48

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

Question 49

selective sweep

Answer 49

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

Question 50

size of selective sweep footpring

Answer 50

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

Question 51

IGF1 dogs

Answer 51

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

Question 52

short legged dogs

Answer 52

have little genetic diversity because we selected for the short legs and weeded a lot of diversity out breeding these linked traits in

Question 53

extreem Fst outliers

Answer 53

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

Question 54

dog wolf selection sweeps

Answer 54

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

Question 55

if selection is so efficient at weeding out bad mutations and fixing good ones why do we still have genetic dx

Answer 55

• hitchhiking
• pleiotropy
• drift

Question 56

hitchiking

Answer 56

deleterious mutations hat would be lost by selection rise in frequency via hitchhiking if linked to positively selected traits

Question 57

Dalmatian stones

Answer 57

linked to spots so select for spots select to be prone to stones

Question 58

pleiotroy

Answer 58

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

Question 59

drift

Answer 59

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)

Question 60

epistasis

Answer 60

selected variants often interact with each other (copy number variant leads to squamous cell carcinoma in digit in black but not white poodles

Question 61

predicatble

Answer 61

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)

Question 62

gene x environment interactions

Answer 62

genetic variants may respond differently to different environments

Question 63

selection on rare recessive variants

Answer 63

selection is very inefficient since these variants are v seldom homozygous and thus seldom have phenotypic effect