lectures 11-20 Flashcards
Quantitative traits
influenced by many loci
often interact with the environment
quantitative genetics
study of the genetic mechanisms of continuous phenotypic traits
Heritability
the proportion of a populations phenotypic variance that is attributes to genetic differences
measured in a particular population at a particular place and time
population parameter not a feature of individuals
H2 =
Broad sense heritability
genetic variance (Vg)/phenotypic variance (Vp)
SNPs
Single-nucleotide polymorphisms (SNPs) are variations in a single nucleotide that occur at a specific position in the genome.
How many SNP’s contribute to human height
10,000
Vp =
phenotypic variance
VG+VE
VG
variance due to genetic differences
= VA + VD + VI
VE
variance due to environmental differences
“Common Garden” experiment
put replicates of genotypes in same and different environments and see how and if they differ
Narrow sense heritability
h^2
the proportion of genetic variation that parents can reliably pass on
(cannot pass on dominance, epistatic events or environmental effects)
parent - offspring regression slope
= VA / VA+VD+VI+VE
sources of genetic variation
if the genes are additive vs non-additive
and sex (M orF)
accounts for 18% of variation
sources of Environmental variation
maternal condition
maternal environment
age of mother
parity (birth order)
intangible
accounts for 82% of variation
VA
additive variance
VD
variation in dominance
VI
Variance in Gene interaction
additive
the addition of each allele changes the mean phenotype by the same amount
Dominance
depends on the combination of alleles
represents modification of the heterzygous individual
Epistasis
two or more genes interact to affect a trait
within generation
phenotypic variation and fitness differences (not all parental generations contribute equally)
part of natural selection
Between generation
phenotypic selection is coupled with heritability to produce a genetic response
part of natural selection
long term selection
may eventually exhaust additive genetic variation (Heritability decreases)
continued response depends on new mutational input and/or gene flow
types of selection on quantitative traits
none
directional
stabilizing and
disruptive
directional selection
one extreme is favored and the population mean moves in that direction
reduces variation (not substantially)
Stabilizing selection
the median has the highest fitness
reduces variation
mean value stays the same
disruptive selection
the two extremes are favored
increases variance
population mean does not change
the rate at which a population can respond to selection depends on
strength of selection (S)
and
heritability (h^2), or the proportion of variation that is due to additive genetic variation
R (response to selection)
= h^2 x S
breeders equation
between generation
= X’-Xp (mean phenotypes of offspring generation - mean phenotype of the population
S
strength of selection/selection differential
the difference between the means (mean of selected parents (Xs) - mean of the whole population (Xp))
S = Xs - Xp
within a generation
VGxE
Genotype by environments interaction
variance in the phenotypic trait that is due to different genotypes responding differently to environmental variation
phenotypic plasticity
a single genotype produces different phenotypes depending on the environment
VGxE
allows organisms to respond to unpredictable changes and regularly occurring ones
can be acted upon by evolution (could be favorable if individuals frequently experience different environments )
seen in a wide range of traits
not always adaptive
reaction norm
the phenotypes produced by a single genotype exposed to different environmental conditions
polyphenisms
simple genetic polymorphisms that respond to their environment and produce multiple discrete phenotypes
often due to a theshold sensitivity to the environment
Evolutionary Advantage: Increases survival by allowing rapid adaptation to environmental changes.
Reduces Genetic Constraints: Provides flexibility without requiring genetic mutations.
Influences Ecology & Behavior: Affects predator-prey interactions, social structures, and reproductive success.
norm of reaction
a plot of carefully measured phenotype in a large pool of genetically identical individuals grown under a range of environments
slopes and intercepts of lines are different
genotypes respond to the environments differently
genotypes show same plasticity if
direction and amount of plasticity is about the same (lines are roughly equal)
Linkage group
all of the genes on a given chromosome
what are the maximum and minimum allele recombination rates
r = 0.5 and r = 0
genetic linkage
refers to the linkage of multiple loci due to the fact that they are transmitted through meiosis together
linkage disequilibrium
any time some combination of alleles at two loci occur together more frequently than expected (knowing one enables you to predict the other)
maximum linkage/disequilibrium (D)
D = 0.25
linkage equilibrium equation
expected AB (P(AB)) = frequency of A * frequency of B
Linkage disequilibrium equation
D(AB) = P (AB) - P(A)*P(B)
P(AB) = observed frequency of individuals with both A and B
P(A) = frequency of A
P(B) = frequency of B
D = 0
no linkage disequilibrium (fully recombining )
what eliminates linkage disequilibrium from a population
recombination (breaks down linkage), unless another evolutionary process prevents it
crossing over
note: it takes more than a single generation
causes of linkage disequilibrium
physical linkage, naturals selection, gene flow, assortative mating
how can we use Linkage Disequilibrium
migration or dispersal between populations with different gene frequencies
reconstructing the history of genes withing a population
identify alleles under selection
mapping of genes underlying traits of interest
genes underlying traits
the number of genomic regions that influence a quatitiative trait
Quantitative trait locus
a region of the genome that is correlated with variation in a phenotypic trait
contains the gene and genes linked to it
QTL analysis
uses an experimental cross to create linkage disequilibrium and then use molecular markers throughout the genome to find the regions where there is a statistical association between the phenotype of interest and molecular markers
Two genetically distinct parental lines are selected, typically differing in the quantitative trait of interest (e.g., high vs. low yield in crops).
These parents are crossed to create F1 hybrids, which are then selfed or backcrossed to create segregating populations (e.g., F2, recombinant inbred lines, or backcross populations).
This process shuffles alleles while maintaining large linkage blocks, creating LD that helps track trait-associated genetic regions.
by recombining chromosomes you can find the regions
that contribute to a phenotype
genome wide association studies
type of QTL analysis
looks for correlation between the genotypes at genetic markers and phenotypic traits
uses existing linkage disequilibrium to find association
Needs very large sample sizes
Compare frequency of alleles at each position of the genome for the groups with or without the trait
Gene Homologs
are the result of shared ancestry
Ortholog
is one of two or more homologous genes separated by speciation event
as species split
mutations accumulate independently
multiple rounds of gene duplication can turn
a single gene into a gene family
Paralogs
Homologous genes resulting from duplication events
Coalesce
separate genealogies will eventually join in single ancestor
number of generations = coalescence time
coalescent process
amount of time alleles take to coalesce depends on drift and selection
alleles will take longer to coalesce in larger populations because drift is weaker, purifying selection is strong or there is little selection,
faster when Ne is smaller
positive selection can accelerate the rise in the frequency of beneficial allele leading to shorter coalescence time for
varies for different genes
gene trees
will not always match species tree
alternative alleles can persist in populations for long time periods
alleles may be passed down in ways that do not reflect the actual branching history of species
incomplete lineage sorting
results in gene trees that differ from true phylogenies
Census N
number of individuals in a population
Ne
the idealized constant population size that matches the extent of drift in the population
the number of individuals in an ideal population in which the rate of genetic drift would be the same as it is in the actual population
reduced by anything that causes variance in progeny production among individuals
usually sever orders of magnitude leass than N ( because of Biased sex ratios, nonrandom mating, selection and fluctuations in population size)
genomics
the study of the structure and function of the genome
mapping genes, DNA sequencing
variation in genome size
bacterial genome size is dependent mainly on number of genes
Eukaryotic genomes vary more in size due to noncoding DNA
positive selection
increases the allele frequency in a population
occurs when an allele is beneficial and has high average fitness
very rare
negative selection/purifying selection
decreases the frequency of an allele in a population
occurs when an allele is deleterious or harmful and has a low average fitness
genes under this selection typiclly evolve very slowly and are conserved for long periods of time
why might selection be weaker when it comes to molecular evolution
lots of regions of DNA do not code for proteins
Not all DNA variation results in protein variation
not all protein variation results in phenotype variation
not all phenotype variation results in a change in fitness
neutral theory of molecular evolution
not true
most mutations are selectively neutral
fixation of these mutations occurs through genetic drift not selection
as a result the substitution of alleles at the molecular level happens at a constant rate (alleles are fixed)
the nearly neutral theory of molecular evolution
we know that many loci are not selectively neutral
need to consider how drift and selection interact
holds fr most DNA and predicts that neutral mutations will yeild nucleotide substitution at a rate equivalent to the rate of mutation
molecular clock
based on the nearly neutral theory
if we know the mutation rate we can use the number of base pair substitutions to estimate the time since two groups shared a common ancestor
linearity in the graph indicates that the rate of divergence is approximately constant/evolving neutrally (number of subs in the gene, by, time since common ancestor)
Methods to detect selection at the molecular level
dN/dS, Fst outliers and selective sweeps
dN/dS
increased substitution rates that alter gene function within a species compared to neutral expectation
Fst outliers
measures gene flow between population by looking at differences in allele frequencies
selective sweep
extended linkage disequilibrium around the beneficial allele and a decrease in genetic variation around the selected site
synonymous mutation
dS: does not change the amino acid sequence of the protein (should evolve at a neutral rate )
mutation in the third position
Non-synonymous mutation
dN: alters the amino acid sequence of the protein
faster evolution than dS indicates positive selection
slower evolution than dS indicates purifying selection
same rate evolution indicates neutral evolution
mutation in the first or second position
dN =
non-synonymous subs / non synonymous sites
dS =
synonymous subs / synonymous sites
dN = dS or dN/dS = 1
neutral evolution
dN>dS or dN/dS>1
positive selection
dN<dS or dN/dS<1
purifying selection
the rate of synonymous subs in a gene serves as an estimate of the rate of
neutral selection
selecting detection using Fst outlier methods
when freuency of an allele differs between populations more than other alleles then it siggests that another process is procducing the extreme outliers
likely to be regions experiencing strong selection
detecting selection using selective sweep
the process by which strong selection for a beneficial allele reduces the genetic diversity of the surrounding nucleotide sequence because linkage causes nearby neutral markers to be “swept along” as selection increases the frequency of the beneficial allele.
gene duplication
major mechanism to generate new genetic material during molecualr evolution
how does gene duplication occur
unequal crossing over during meiosis
replication slippage by DNA polymerase
retro transposition of mRNA reverse transcribed into DNA
possible outcomes of gene duplication
second copy takes on a new function (Neofunctionalization)
the two copies split the function (sub functionalization)
the two copies both continue with the same function (gene conservation)
second copy becomes non-functional (Nonfunctionalization)
complex adaptations
suites of co-expressed traits that together experience selection for a common function
often have regulatory networks
Novel traits can arise when…
existing genes are expressed in a new developmental context
can also arise from a series of duplication events followed by co-option of proteins originally involved with other body functions (snake venom)
why do duplicated genes accumulate mutations rapidly
they are released from purifying selection
gene recruitment
the co-option of genes for a totally different function as a result of mutation
what does it mean when the species phylogeny does not math the gene genealogy
they do not have the same evolutionary history
planting refuges
if all plants were Bt plants then selection would lead to all resistant insects
Mixtures of Bt plants and Non-Bt plants leads to a mixture of resistant and non resistant insects
relies on:
Resistance recessive
gene flow
population size
random mating
and the cost of resistance
Antagonistic pleiotropy
a mutation or gene with beneficial effects for one trait also causes detrimental effects on other traits
constraint on evolution
genetic correlations between traits are caused by
correlated selection for suites of coordinated traits
genes may act independently on the two traits but they are physically linked and in linkage disequilibrium
genes that influence one trait may also influence another trait (pleiotropy)
Apart from the moral and ethical issues, eugenics is fundamentally flawed because:
1) the “nature vs. nurture” dichotomy is a fallacy
2) although many traits have high heritability, heritability measures are specific to the population and environment in which it is measured
3) the kind of traits eugenicists seek to select on are seldom due to simple genetic architectures
what are pseudogenes and how to they form
Pseudogenes are non-functional copies of genes that have lost their ability to code for proteins due to mutations. They arise from functional genes but accumulate changes that prevent them from being expressed properly.
Mutations: Nonsense, frameshift, or deletions disrupt the gene’s coding sequence.
Loss of Regulatory Elements: Without promoters or enhancers, transcription fails.
Reverse Transcription: mRNA is copied back into DNA and inserted, but lacks regulatory sequences
