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ANTH 3100
Week 4!
How evolution works at the genetic level
Chapter 5
Raw material: heritable variation among
individuals
Eukaryotic DNA is organized into
chromosomes
Chromosomes come in homologous
pairs
Ploidy can vary
Ploidy: Number of copies of unique chromosomes in a cell
Polyploidyhasinterestingeffectontheimpactofselection
6
DNA codes for protein
Mutation: any change to
the genomic sequence
Production of protein from DNA requires
transcription and translation
Gene expression: process by which information from a gene is
transformed into product
Proteins are chains of amino acids
Ribosomes translate mRNA into protein
The Amino Acids and their codons…
Gene expression can be regulated in a
number of ways
cis-regulatory
elements(CREs)
areregionsofnoncodingDNAwhich
regulatethe
transcriptionof
nearbygenes.The
Tataboxisoneof
theseregulators.
RNA splicing can create multiple
proteins from a single gene
Regulation of gene expression is flexible
by
d
lyze
a
t
ca
e
me
y
z
n
s!
Neutral genes?
Non protein coding
DNA
More than 98% of human DNA DOES NOT CODE FOR
PROTEINS
Noncoding functional RNA!
ribosomal RNA, transfer RNA, and others!
!
Cis- and Trans-regulatory elements!
Control the transcription of genes.!
Introns!
Introns are non-coding sections of a gene, transcribed into the precursor mRNA sequence, but ultimately removed by
RNA splicing during the processing to mature messenger RNA. Many introns appear to be mobile genetic elements.!
Are some of these selfish genetic elements that are neutral to the host because?!
Pseudogenes!
Pseudogenes are DNA sequences, related to known genes, that have lost their protein-coding ability or are otherwise no
longer expressed in the cell. These account for a large proportion of the genomic sequences in many species. !
Mobile genetic elements!
Transposons are ofter referred to as ‘wild’ DNA, and can sometimes have mild deleterious effects.
Non-protein coding regions make up
most of the genome
• Non-protein coding
regions include:
– RNA genes
– Pseudogenes
– Mobile genetic
elements
microRNA can affect phenotypes
Variation in genome size and complexity
Most variation in size due to differences in mobile genetic elements
Key Concepts
• Most proteins function in 5 main ways:
– Structure (hair, nails, muscle, bone, collagen, etc.)
– Enzymatic - catalysis; increase speed of chemical
reactions
– Regulation - stimulate/hinder other proteins or expression
of genes.
– Transportation - act as channels & pumps
– Defense & Offense - antibodies, etc.
• Mutations are the raw material for evolution
• In diploid and polyploid organisms, deleterious
mutations may be masked by a functional gene copy
Key Concepts
• All cells use mRNA to carry genetic
information
– Some viruses use RNA instead of DNA for the
genome
• Non-coding RNA plays critical roles in gene
regulation
Mutations
Arise from errors in copying, damage sustained by DNA
incurred during its use in cellular processes, and by
transposons.
!
Transposons: mobile elements in the genome (independent
genes?)
!
Mutations occur independent of their fitness value.
!
Mutation rates vary between species.
!
Most mutations that effect phenotype are probably not helpful.
Types of mutation
Mutation
Synonymous/Non-synonymous
Different types of mutation can alter the
phenotype
closetoaffected
region
farfromaffected
region
What would you expect to be the difference in outcome if a mutation
occurred in a protein coding region of DNA vs. a non-protein coding
region? If it DID occur in a protein coding region, what would you
expect the differences to be between a region that coded for a
structural protein vs. one that coded for a transcription factor?
PAPER TOPIC
29
Example of point mutation in a protein
coding gene.
Example of mutation
in regulatory genes
Bones from the atavistic
hind-limbs of a humpback
whale.
33
34
Germ line mutations are heritable
• Somatic mutations: affect cells in the
body of an organism; not heritable
!
!
!
!
• Germ-line mutations: affect gametes;
heritable and relevant to evolution
Most mutations are neutral or deleterious
Mutations
TRPV1 protein
TRPV1isanonselectivecation
channelthatmaybeactivatedbya
widevarietyofexogenousand
endogenousphysicalandchemical
stimuli.Thebest-knownactivators
ofTRPV1are:temperaturegreater
than43°C(109°F);acidic
conditions;capsaicin,theirritating
compoundinhotchillipeppers;
allylisothiocyanate,thepungent
compoundinmustardandwasabi.
Key Concepts
• Changes in coding sequences and noncoding sequences are ‘heritable’
• Gene expression changes can affect when,
where, and how much a gene is expressed
Recombination generates variation
Independent assortment ensures novel
combinations of alleles
Recombination
Sequence changes arise due to recombination
Key Concepts
• Meiosis distributes alleles through a
population and generates considerable
genetic variation
– Recombination / Independent assortment
Linking genotype and phenotype
• Genotype: the genetic make-up of an
individual
• Phenotype: an observable measurable
characteristic of an organism
Genetics/Mendel Movie
47
Simple polymorphisms can produce
differences in phenotype
Sometimes a single genotype can
produce multiple phenotypes
Polyphenic trait: single
genotype produces
multiple phenotypes
depending on
environment
Norm of reaction
Canalization
Phenotypic
plasticity
Human height has genetic component
Most features polygenic
53
Key Concepts
• Polyphenisms often result from a
developmental threshold mechanism
• Continuously varying traits are called
quantitative traits
• Evolutionary biologists study variation in
the expression of phenotypic traits caused
by genetic and environmental factors
Environmental influences on gene
expression
• Phenotypic plasticity: changes in
phenotype produced by a single genotype
in different environments
– Tailors organism to environment
Key Concept
• Gene expression often influenced by
signals from the environment
– Allows match to environmental circumstances
Example of environmental influence on
gene expression
The‘Himalayangene,’
activatedinwarm
conditions,regulatesthe
productionofmelanin.
Developmental canalization
Chapter 6
The ways of change: drift and selection
Population genetics
• Study of the distribution of alleles in
populations and causes of allele frequency
changes
What
is
variation?
‘Types’ or ‘typological
thinking’
vs.
‘Genetic thinking’
Key Concepts
• Diploid individuals carry two alleles at
every locus
– Homozygous: alleles are the same
– Heterozygous: alleles are different
• Evolution: change in allele frequencies
from one generation to the next
Mendel’s
peas
64
Hardy-Weinberg equilibrium
• Population allele frequencies do not
change if:
– Population is infinitely large
– Genotypes do not differ in fitness
– There is no mutation
– Mating is random
– There is no migration
Predictions from Hardy-Weinberg
• Allele frequencies predict genotype frequencies
which, in turn, predict phenotype frequencies
%dominantalleles+%recessivealleles=100%
p+q=1
*AND*
p2 + 2pq + q2 = 1
Y
y
Y
YY% + Yy% + yY% + yy% = 100%
y
(4/25) + 2*(6/25) + (9/25) = 1
.16 + .24 + .24 + .36 = 100%
.4+.6 = 1
Predictions from Hardy-Weinberg
Albinism is a rare genetically inherited trait that is only expressed in the phenotype of homozygous
recessive individuals (aa). The most characteristic symptom is a marked deficiency in the skin and hair
pigment melanin. This condition can occur among any human group as well as among other animal
species. The average human frequency of albinism in North America is only about 1 in 20,000.
Referring back to the Hardy-Weinberg equation (p² + 2pq + q² = 1), the frequency of homozygous
recessive individuals (aa) in a population is q². Therefore, in North America the following must be true for
albinism:
q² = 1/20,000 = .00005
By taking the square root of both sides of this equation, we get:
rounded off for simplification.)
q = .007
(Note: the numbers in this example are
In other words, the frequency of the recessive albinism allele (a) is .00707 or about 1 in 140. Knowing
one of the two variables (q) in the Hardy-Weinberg equation, it is easy to solve for the other (p).
The frequency of the dominant, normal allele (A) is, therefore, .99293 or about 99 in 100.
!
p=1-q
p = 1 - .007
p = .993
The next step is to plug the frequencies of p and q into the Hardy-Weinberg equation:
!
p² + 2pq + q² = 1
(.993)² + 2 (.993)(.007) + (.007)² = 1
.986 + .014 + .00005 = 1
This gives us the frequencies for each of the three genotypes for this trait in the population:
p² = predicted frequency
of homozygous
dominant individuals
2pq = predicted frequency
of heterozygous
individuals
q² = predicted frequency
of homozygous
recessive individuals
(the albinos)
= .986 = 98.6%
= .014 = 1.4%
= .00005 = .005%
Key Concepts
• Hardy-Weinberg theorem proves that allele
frequencies do not change in the absence
of drift, selection, mutation, and migration
• Mechanisms of evolution are forces that
change allele frequencies
Polymorphic:
• possessing more than one allele for a given
locus
generation
Variation can be described
in allele frequencies
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One gene, polymorphic
Multiple
genes,
polymorphic
Multiple genes,
polymorphic
Populations evolve through a variety of
mechanisms
Key Concept
• Hardy-Weinberg serves as the
fundamental null model in population
genetics
Genetic drift causes evolution in finite
populations
Genetic drift results from random
sampling error
Sampling error is higher with smaller sample
Genetic drift is stronger in small
populations
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Drift reduces genetic
variation in a population
• Alleles are lost at a faster
rate in small populations
– Alternative allele is fixed
Wright-Fisher model
!
Population size and
Evolutionary processes
84
Key Concepts
• Genetic drift causes allele frequencies to
change in populations
• Alleles are lost more rapidly in small
populations
Population bottlenecks
Founder effect
Bottlenecks reduce genetic variation
A bottleneck causes genetic drift
Rare alleles are likely to be lost during a
bottleneck
Founder effect
Founder effects cause genetic drift
Key Concept
• Even brief bottlenecks can lead to a drastic
reduction in genetic diversity that can
persist for generations
The concept of fitness
• Fitness: the reproductive success of an
individual with a particular phenotype
• Components of fitness:
– Survival to reproductive age
– Mating success
– Fecundity
• Relative fitness: fitness of a genotype
standardized by comparison to other
genotypes
Contribution of alleles to fitness
• Average excess fitness: difference
between average fitness of individuals with
allele vs. those without
Natural selection more powerful in large
populations
• Drift weaker in large populations
• Small advantages in fitness can lead to
large changes over the long term
Pleiotropy may constrain evolution
• Pleiotropy: mutation in a single gene
affects many phenotypic traits
– Can be antagonistic
– Net effect on fitness determines outcome of
selection
Pesticide resistance and pleiotropy
Pesticide resistance and pleiotropy
Experimental evolution provides
important insights about selection
Natural selection in action
Alleles that lower fitness experience negative selection
!
Alleles that increase fitness experience positive selection
Relationships among alleles
• at a locus
• Additive: allele yields twice the phenotypic
effect when two copies present
• Dominance: dominant allele masks presence
of recessive in heterozygote
!
• more than one locus
• Epistasis: effects of one allele modify the
effects of another
• Dominance
• Additive
Effects of selection on different types of
alleles
Epistasis
Pitx 1 gene expression is stickleback fish.
!
For this reason, combinations of genes can produce more than just an additive effect.
!
The gene whose phenotype is expressed is said to be epistatic, while the phenotype
altered or suppressed is said to be hypostatic.
Mutation generates variation
• Mutation rates for any given gene are low
• But, considering genome size and
population size many new mutations arise
each generation
– Estimate in humans: 9.8 billion new mutations
• Source of variation for selection and drift to
act
Mutation-selection balance
• Equilibrium frequency reached through tugof-war between negative selection and new
mutation
• Explains persistence of rare deleterious
mutations in populations
Balancing selection
• Some forms of selection maintain diversity
in populations:
– Negative frequency-dependent selection
– Heterozygote advantage
Negative frequency-dependent
selection
non-synonymous
mutation
synonymous
mutation
heterozygous sickle cell
normal red blood cells
Homozygous sickle cell
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Predictions from Hardy-Weinberg
Sickle Cell Anemia is a genetically inherited trait that is only expressed in the phenotype of homozygous
recessive individuals (aa). Sickle-cell disease is common in many parts of India and Africa, where the
prevalence has ranged from about 5 to 20% in endemic areas. For this we will use 16% as our number of
HOMOZYGOTIC RECESSIVES, people with sickle cell disease.
Referring back to the Hardy-Weinberg equation (p² + 2pq + q² = 1), the frequency of homozygous
recessive individuals (aa) in a population is q². q² = .16
By taking the square root of both sides of this equation, we get:
rounded off for simplification.)
q = .4
(Note: the numbers in this example are
In other words, the frequency of the recessive sickle cell allele (a) is .4 or about 1 in 25. Knowing one of
the two variables (q) in the Hardy-Weinberg equation, it is easy to solve for the other (p).
The frequency of the dominant, normal allele (A) is, therefore, .6 or about 6 in 100.
!
p=1-q
p = 1 - .4
p = .6
The next step is to plug the frequencies of p and q into the Hardy-Weinberg equation:
!
!
p² + 2pq + q² = 1
(.6)² + 2 (.6)(.4) + (.4)² = 1
.36 + .48 + .16 = 1
This gives us the frequencies for each of the three genotypes for this trait in the population:
q² = predicted frequency
of homozygous
RECESSIVE individuals (Those with sickle cell disease)
2pq = predicted frequency
of heterozygous
individuals
p² = predicted frequency
of homozygous
DOMINANT individuals
= .16 = 16%
= .48 = 48%
= .36 = 36%
Heterozygote advantage and sickle-cell
anemia
Key Concepts
• Selection occurs when genotypes differ in
fitness
• Outcome of selection depends on
frequency of allele and effects on fitness
• Population size influences power of drift
and selection
– Drift more powerful in small population
– Selection more powerful in large population
Key Concepts
• Alleles may have pleiotropic effects
– When fitness effects oppose each other
environment determines direction of selection
• Laboratory evolution studies reveal how alleles
rise and spread through populations
• Rare alleles almost always carried in a
heterozygous state
– Recessive alleles invisible to selection
– Selection cannot drive dominant to fixation
Key Concepts
• Mutations are the source of new genetic
variation in populations
– Can be many in a large population
• Balancing selection maintains multiple
alleles in populations
– Negative frequency-dependent
– Heterozygote advantage
Inbreeding and the Hapsburg dynasty
Inbreeding coefficient
• Probability that two alleles are identical by descent
Inbreeding depression results in
reduced fitness
• Rare deleterious alleles more likely to
combine in homozygotes
Key Concepts
• Alleles are identical by descent if they both
descended from a single mutational event
• Inbreeding increases percentage of loci
that are homozygous for alleles identical by
descent
• Genetic bottlenecks often go hand in hand
with inbreeding and selection
– Recessive alleles exposed to selection