Chapter 13Chapter 13

Genetic VariationGenetic Variationin Populationsin Populations

Figure CO: An Figure CO: An albino whitetail fawnalbino whitetail fawn © Srcromer/Dreamstime.com

Overview• Genetic variation arises from random

mutations• Mutation rates vary• Some loci are more likely to mutate than

others• In the short term, when microevolution

operates, the frequency of different alleles in the population from prior mutations is more important than the creation of new mutations

Overview• The ability of DNA to repair itself also limits the

impact of new, potentially harmful, mutations• Quantitative trait loci (QTL) that contain groups

of genes often influence phenotypic characters that show continuous variation

• Genetic Drift and Gene Flow also impact the genome composition/gene pools of populations

• The genetic history of populations contributes to our understanding of patterns of species distributions

Mutation

• Mutation is occurs in all populations• New mutations that arise, if not neutral in

effect, will rarely be better, and likely will be worse, than the alleles already present

• Changes in environmental conditions can elicit a genetic response based on the available genetic variation in a population (evolution)

Resistance to DDTin Common Houseflies

• Rapid genetic changes occur in many insect populations exposed to pesticides such as dieldrin and DDT

Adapted from Strickberger, M. W. Genetics, Third edition. Macmillan, 1985; based on data from Decker, G. E., and W. N. Bruce, Amer. J. Trop. Med. Hygiene 1 (1952): 395-403.

Figure 01_INS: Resistance to DDT in common houseflies

© Frank B. Yuwono/ShutterStock, Inc.

• Both dieldrin and DDT are neurotoxins; DDT opens sodium channels and both DDT and dieldrin stimulate Ach synthesis and release

• Resistance develops when mutant neuron membrane proteins arise or the numbers of receptors change

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Selection for Pesticide Resistance

Decreased PesticideUptake

Decreased PesticideTargets

Resistance to DDT in Fruit Flies• Experimental populations

were bred by hybridizing a resistant and a susceptible strain of D. melanogaster

• Resistant genes were found on three chromosomes (2, 3, and X)

• Resistance was cumulative; the more genes contributing to resistance, the greater the resistance Figure 02: Percent survival of fruit flies

Adapted from Crow, J. F., Ann. Rev. Entomol., 2 (1957): 227-246.

Peppered Moth Biston betularia(Linnaeus, 1758)

• The peppered moth occurs in two color phases (a) Both phases are displayed against an unpolluted, lichen-covered

tree (b) Both phases are displayed against a dark tree, on which the

lichen were killed by pollution

Peppered Moth Biston betularia• The typical wildtype white/speckled phenotype is

caused by a recessive allele that must be homozygous to be expressed

• The recessive allele predominates in wild population gene pools

• The melanic or black form is caused by a dominant allele that occurs spontaneously in nature

• Peppered moths rest on trees and depend on camouflage for protection

Peppered Moth Biston betularia

• In unpolluted areas, trees are covered in lichens and the light form of the moth is hard to see

• In the mid 1800’s, air pollution in British cities covered trees with coal dust and soot

• In Victorian era cities, the dark form became common and the light form rare

Peppered Moth Biston betularia

• In 1848, 5% of the population were dark colored moths while 95% were light colored

• In 1895, 98% were dark colored while 2% were light colored• In 1995, 19% were dark colored while 81% were light

colored

Peppered Moth Biston betularia• The melanic phenotype is due to underlying homozygous (BB) and

heterozygous (Bb) dominant genotypes• In the mid 1950’s, air pollution controls were introduced in Britain• When smoke pollution decreased in Britain, natural selection acted

very quickly to favor survival of the wild type peppered morphs as bird predation eliminated melanic forms in progressively less polluted forests

• The frequency of the melanic form has declined ever since

Bernard Kettlewell (1907-1979) and Industrial Melanism

Kettlewell performed extensive field studies in Britain in the 1950s to test the hypothesis that bird predators were altering the frequencies of the color morphs based on the moths’ contrast to their backgrounds, such as tree bark, when they were at rest

Kettlewell’s Experiments

• Aviary studies demonstrated that native birds did eat peppered moths

• Release and capture studies in two areas indicated that peppered forms survived in greater numbers in unpolluted forests while melanic forms survived in greater numbers in soot polluted forests

• Kettlewell also observed birds preying on the two colors morphs in nature

Kettlewell’s Experiments• Many other lepidopterists have confirmed

Kettlewell’s conclusions

• Kettlewell continued to work with melanism throughout his career

• Kettlewell summarized his career’s work in The Evolution of Melanism: a study of recurring necessity; with special reference to industrial melanism in the Lepidoptera (1973)

Kettlewell’s Experiments• In Bernard Kettlewell’s famous experiment, he

placed moths on dark and pale tree trunks and showed that background colors strongly influenced survival

• In the wild, however, moths take much more care about where they settle and rarely settle on large tree trunks

• Instead moths usually choose to rest in shady areas where branches join the trunk

• If the moth’s choice of site is adaptive, then moths in these positions should be taken less often by predators than those on open space tree trunks

Peppered Moths• In an experiment in which dead moths were pinned to

open tree trunks or the underside of branches birds consumed fewer of those on the undersides of branches

Peppered Moths• Other moths also make

very specific choices about where to rest

• The speckled moth usually perches head up with its forewings covering its body

• When given a choice of resting site these moths prefer birch trees

Peppered Moths• Pietrewicz and Kamil (1977) tested

whether these choices by moths were selectively advantageous

• They trained blue jays to respond to slides of moths by pecking a button for a food reward whenever they spotted a moth

• Results showed that blue jays spotted moths less often on birch trees and especially when a moth was oriented with its head up

Thus, moth’s choices appear to reduce the risk of detection by visually oriented predators

Try TechApps to hunt moths yourself!

Kettlewell’s Critics: Scientists

• A minority of serious scientists have criticized various aspects of Kettlewell’s methodology in his industrial melanism studies

• But the scientific consensus remains that Kettlewell‘s work was valid and that Kettlewell had demonstrated microevolution in action

Kettlewell’s Critics: Others• British journalist Judith Hooper

attacked Kettlewell in her book, but her book has been dismissed by scientists for lack of scientific understanding, prejudice and careless journalism

• Creationists have seized on the criticisms and claim that not only was Kettlewell’s work invalid but also that what he claimed did not demonstrate evolution since it did not document the origin of a new species

Mutation Rates• Mutation rate is the probability that a gene will mutate when

the cell divides

• A spontaneous mutation rate for E. coli = 1 in 109 replicated base pairs or 1 in 106 replicated genes

• 1 in a million is easy to acheive in bacterial colonies

• Mutagens increase the mutation rate by 10 - 1000 times to as high as 1 in 103 replicated genes

Mutation Rates

• Though most mutations are harmful, rare superior mutation rates are advantageous

• The mutation rates observed in nature allow populations to retain common adaptive phenotypes while accumulating new alleles which might contribute to the origin of new features in a few individuals

• A remarkable way in which some organisms accumulate mutations without experiencing their immediate effects is to bind their mutant gene products with heat shock proteins

Heat Shock Proteins (HSPs)

• Heat shock proteins (HSP) are expressed in response to various biological stresses, including heat, high pressures, and toxic compounds

• HSPs are among the most abundant cellular proteins found under non-stress conditions

Heat Shock Proteins (HSPs)• HSPs include a family of proteins

known as "chaperones," which are solely dedicated to helping other proteins fold and assume their proper functions

• Cells are efficient about getting the folding right because misfolded proteins can change the normal life of the cell– In some cases change is good, in

others deadly

Heat Shock Proteins in Protein Folding

• As the ribosome moves along the molecule of messenger RNA, a chain of amino acids is built up to form a new protein molecule

• The chain is protected against unwanted interactions with other cytoplasmic molecules by heat-shock proteins and a chaperonin molecule until it has successfully completed its folding  

Source: (http://www.cs.stedwards.edu/chem/Chemistry/CHEM43/CHEM43/HSP/FUNCTION.HTML)

Heat Shock Proteins (HSPs)

• Heat shock proteins may be disabled in new stressful environments– dramatic change in temperature– dramatic change in pH– dramatic change in salinity– etc.

• When the HSPs are disabled, mutant proteins may develop into new conformations

• These new shapes may permit new functions, which may allow natural selection to improve the mutant proteins over time

Neo-Darwinism and Genetic Polymorphism

• New beneficial mutations seem to be very rare

• Neutral or deleterious but recessive mutations provide a reservoir of potential genetic variation

• Genetic variation in a population, where two or more alleles exist at a locus, is termed a genetic polymorphism

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• Morphology, Physiology, Behavior– Size, color, shape of cell or body parts,

etc.– Respiration, digestion, excretion, etc.– Nutrient acquisition, reproduction,

migration, etc.

• Enzyme polymorphism– Change in catalytic ability due to change

in temperature, osmotic environment, pH, etc.

• DNA sequence polymorphism– Changes in bases, codons, introns,

exons, etc.

Genetic Variation in Nature

Neo-Darwinism and Genetic Polymorphism• In the fruit fly, Drosophila pseudoobscura,

populations in different localities are polymorphic for a wide variety of gene arrangements

• Many linked alleles are protected inside inversion loops

Figure 03B: Chromosomal inversions found at different months during the year in one locality, Mount San Jacinto, California

Adapted from Dobzhansky, T., Heredity 1 (1947): 53-64.

Drosophila pseudoobscura Polymorphisms• The different inversion loops contain different linked alleles• Those linked alleles control different metabolic phenotypes• Since a fruit fly lives only about a month, different metabolic phenotypes can be selected over the course of a single season

Figure 03A: Third chromosome gene inversions in Drosophila pseudoobscura

Adapted from Dobzhansky, T., Carnegie Inst. Wash. Publ., 554 (1944): 47-144.

Drosophila pseudoobscura Polymorphisms• Those different phenotypes,

whose linked genes are protected in the inversion loops, are also adapted to different climates in different locations

• The different locations differ in average temperatures, average rainfall, altitude, and other environmental factors

Genetic Polymorphism• Genetic polymorphism provides a much

greater source of genetic variation than do the relatively few new mutations that arise each generation

• Now let’s look again at the nature of genetic variation

Polygenic Inheritance• Polygenic inheritance, also known as quantitative or

multifactorial inheritance, refers to inheritance of a phenotypic characteristic (trait) that is attributable to two or more genes, or to the interaction with the environment, or both

• Unlike monogenic traits, polygenic traits do not follow patterns of simple Mendelian inheritance (discontinuous traits)

• Instead, their phenotypes typically vary along a continuous gradient depicted by a bell-shaped curve (a normal distribution)

Continuous Variation

• Small heritable changes provide most of the variation on which natural selection acts

Figure 04: Heights of 1,000 Harvard College students aged 18 to 25Adapted from Castle, W. E. Genetics and Eugenics, Fourth

edition. Harvard University Press, 1932.

Continuous Variation

It is almost impossible for a single gene locus to control continuous variation

Population Genetics• The study of genes and

genotypes in a population• We want to know the

extent of genetic variation, why it exists and how it changes over time

• This knowledge helps us to understand how genetic variation is related to phenotypic variation

Gene Pool• The gene pool is all of the

genes and different alleles in a population

• We study genetic variation within the gene pool and how genetic variation changes from one generation to the next

Emphasis is often on variation in alleles between members of a population at certain loci of interest

Populations• Group of individuals of the same species that can

interbreed with one another• Some species occupy a wide geographic range and

are divided into discrete populations (demes)

Genes in Natural PopulationsAre Usually Polymorphic

• Polymorphism – many phenotypic traits display variation within a population– Due to 2 or more alleles at a locus that influence a phenotype

• Polymorphic gene/locus - 2 or more alleles• Monomorphic gene/locus– predominantly a single allele

[“fixed” locus]• Single nucleotide polymorphism (SNPs)

– Smallest type of genetic change in a gene; a point mutation– Most common – 90% of the variation in human gene sequences

• Large, healthy populations exhibit a high level of genetic diversity

• Polymorphisms are the raw material for evolution

Quantitative Trait Loci (QTL) • The term quantitative trait

loci (QTL) is shorthand for all of the loci or genes (alleles) in a particular region of a chromosome that affect a quantitative aspect of the phenotype

• In sticklebacks, Gasterosteus aculeatus, there is variation in the pelvic girdle and in dermal plates

Figure 06: Three spine sticklebacks

Reproduced from Trends in Ecology & Evolution, 19(9), Foster, S. A, and Baker, J. A., Evolution in parallel…, pp. 456–459, copyright 2004, with permission from Elsevier. Photographs courtesy of Dr. W. A. Cresko, University of Oregon.

QTL Mapping• Statistical analysis is required to demonstrate that different

genes interact with one another and to determine whether they produce a significant effect on the phenotype

• QTL mapping identifies a particular region of the genome containing a gene that is associated with the trait being measured

• QTLs are shown as intervals across a chromosome where the probability of association is plotted for each marker used in the mapping experiment

• The QTL techniques were developed in the late 1980s and can be performed on inbred strains of any species

• QTL analysis allows scientists to quantify the contributions of both heredity and environment to polygenic traits

Population Genetics• In our introductory course, we are not going

to explore the molecular details of QTL analysis

• Instead, we will examine the foundation of population genetics, the Hardy-Weinberg Equilibrium

Population Genetics and Gene (Allele) Frequencies in Populations

• The Neo-Darwinian theory– Evolution is a population phenomenon– Evolution is a change in gene (now allele) frequencies

in a population because of various natural forces such as mutation, selection, migration, or genetic drift

– These changes in allele frequencies lead to differences among populations, species, and higher clades

– This population genetics view of evolution became known as Neo-Darwinian theory with its emphasis on the frequency of genes and alleles in populations

• A population’s gene pool includes all the alleles for all the loci present in the population

• Diploid organisms have a maximum of two different alleles at each genetic locus

• Typically, a single individual therefore has only a small fraction of the alleles for a given locus that are present in the population as a whole

Allele Frequencies

Allele and Genotype Frequencies• Related but distinct calculations

• Population 1 has 5 homozygous dominant and 5 heterozygous individuals

• Population 2 has 7 homozygous dominant, 1 heterozygous, and 2 homozygous recessive individuals

• Both populations have identical allele frequencies, 15 A : 5 a = 75% A and 25% a alleles

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Godfrey H. Hardy: English mathematician (1903)Wilhelm Weinberg: German physician (1908)W.E. Castle: American geneticist (1908) (left out)

Working independently just a few years after the rediscovery of Mendelian genetics they concluded that:

The original proportions of the allele frequencies in a population remain constant from generation to generation as long as five assumptions are met

The Hardy-Weinberg Principle

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Five H-W Equilibrium assumptions: If: 1. The population size is very large2. Random mating is occurring3. No mutation occurs4. No selection occurs5. No alleles transfer in or out of the population

(no migration occurs)Then allele frequencies in the population will

remain constant through future generations

The Hardy-Weinberg Principle

1) diploid organisms 2) sexual reproducing organisms 3) generations are non-overlapping 4) all genotypes are equally viable

• If these simplifying assumptions are not met, it complicates the mathematics for the analyses• Whether or not these assumptions are all met, biologists can use Mendelian ratios and Hardy-Weinberg analysis to measure rates of evolution

Simplifying Assumptions forThe Hardy-Weinberg Principle

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• p = frequency for first allele in the population’s gene pool

• q = frequency for second allele in the population’s gene pool

• Calculate allele frequencies with a binomial equation:

p + q = 1• because there are only two alleles:

p + q must always equal 1 (100% of the alleles)

• [Note: more alleles can be handled, e.g., with three alleles: p + q + r = 1]

The Hardy-Weinberg Principle

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Calculate genotype frequencies with a binomial expansion

(p+q)2 = p2 + 2pq + q2 = 1• p2 = individuals homozygous for first allele• 2pq = individuals heterozygous for the alleles• q2 = individuals homozygous for second allele

• because there are three phenotypic classes: p2 + 2pq + q2 must always equal 1

The Hardy-Weinberg Principle

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The Hardy-Weinberg Principle

p = 0.6 and q = 0.4 and therefore p + q = 1.0

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Product Law of Probability: The probability of two independent events occurring simultaneously is equal to the product of their separate probabilities

Product Law of Probability

Male gamete production is independent of female gamete production

54use the Hardy-Weinberg equation to predict frequencies in subsequent generations

The Hardy-Weinberg Principle

assume 100 viable offspring

36 BB and 48 Bb offspring have (36 + 36 + 24 + 24 = ) 120 B alleles; 48 Bb and 16 bb have (24 + 24 + 16 + 16 = ) 80 b alleles. Freq of B = 124/200 = 0.6 and freq. of b = 80/200 = 0.4.

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If: 1. The population size is very large2. Random mating is occurring3. No mutation occurs4. No selection occurs5. No alleles transfer in or out of the

population (no migration)Then allele frequencies in the population will

remain constant through generations

The Hardy-Weinberg Equilibrium

Another Example • 49 red-flowered RR• 42 pink-flowered Rr• 9 white-flowered rr• [100 diploid individuals

carry 200 alleles]

49 RR and 42 Rr offspring have (49 + 49 + 42 = ) 140 R alleles

42 Rr and 9 rr have (42 + 9 + 9 = ) 60 r alleles

Freq of R = 140/200 = 0.7 and freq. of r = 60/200 = 0.3

No allele freq. change in the F1

The Hardy-Weinberg Equilibrium• Relates allele and genotype frequencies

under certain limiting conditionsp2 + 2pq + q2 = 1 (the Hardy-Weinberg Equation)If we apply the equation to the flower color gene, then:

p2 = the genotype frequency of RR2pq = the genotype frequency of Rr

q2 = the genotype frequency of rrIf p = 0.7 and q = 0.3, then:

Frequency of RR individuals = p2 = (0.7) 2 = 0.49Frequency of Rr individuals = 2pq = (2)(0.7)(0.3) = 0.42

Frequency of rr individuals = q2 = (0.3) 2 = 0.09

The Hardy-Weinberg Equilibrium

• Hardy–Weinberg proportions for two alleles: the horizontal axis shows the two allele frequencies p and q and the vertical axis shows the expected genotype frequencies

• Each line shows one of the three possible genotypes and their relative frequencies

[In H-W equilibrium, heterozygotes will never be greater than 50% of the population]

1. The population size is very large2. Random mating is occurring3. No mutation occurs4. No selection occurs5. No alleles transfer in or out of the population

(no migration occurs)

The Hardy-Weinberg Principles Describes a Population at Genetic Equilibrium

Genetic equilibrium requires:

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Five Agents of Evolutionary Change

A population not in Hardy-Weinberg equilibrium is one in which allele frequencies are changing generation to

generation due to one or more of the five evolutionary agents that are operating in the population

Agents of Evolutionary Change• Small Population Size:

• When a population is large, then allele frequencies are very unlikely to change due to random sampling error

• When a population is small, then, just by chance, some individuals fail to mate at all, not because they are unfit

• When a population is small, then, just by chance, some offspring fail to survive to reproduce, not because they are unfit

• When a population is small, gene frequencies may change due to these sorts of random effects – this is called genetic drift

California condors

Genetic Drift• Genetic drift: Random fluctuations in allele

frequencies over time due to chance events• important in small populations

• founder effect – a few individuals found a new population (with a small allelic pool)

• bottleneck effect – a drastic reduction in population, and gene pool size and complexity

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DNA studies indicate that polar bears have suffered repeated bottleneck events when the arctic climate warmed and also repeated hybridization causing gene introgression (HGT) from their sister group, the brown bears

Genetic Drift• In small populations, allele frequency

changes that have no predictable constancy or direction from generation to generation

• Genetic drift is a consequence of random fluctuations in gene frequencies that arise in small populations

• In this experiment, 107 populations were established with p = q = 0.5 for brown (bw/recessive) and red (+/wildtype/ dominant) eye alleles, but at each generation, only 16 parents were drawn, at random, to produce the next generation

• By generation 19, brown eye had been eliminated from 30 populations and fixed at 100% in another 28 populations.

Figure 08: Numbers of brown (bw75) alleles in 107 populations of D. melanogaster

Data from Buri, P., Evolution 10 (1956): 367-402.

(+/+) (bw/bw)

Table 13.1: Definitions of Genetic Drift and Comments on Them

Regardless of the definition, genetic drift tends to increase variation between populations, but in no particular direction, including not

necessarily to increase the fitness of the population

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Agents of Evolutionary Change• Random Mating is required for the Hardy-Weinberg

Equilibrium• The members of the population mate with each other without

regard to their phenotypes and genotypes• The members of the population are (relatively) equally likely to

mate with any other member of the population of the opposite sex, i.e., have relatively equal access to all members of the population

• Humans mate without regard to ABO and Rh blood types– This example shows that a particular gene can meet the H-W equilibrium

criteria, even though the species as a whole does not• Wind-pollinated plant species and many aquatic species who

release their eggs and sperm into the water• Animals who are members of large mobile schools, herds or flocks

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Agents of Evolutionary Change• Nonrandom Mating: mating between specific

genotypes shifts genotype frequencies

Non-Random mating could be either like with like; also called Assortative Mating or opposites attracting each other; also called Non-Assortative Mating

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Agents of Evolutionary Change• Classification of mating systems

– Monogamy, polygamy, polyandry (Darwin 1871)

– Monogamy, resource defense polygyny, harem defense polygyny, explosive mating assemblage, leks, female access polyandry, etc. (Emlen & Oring 1977)

– Promiscuous– Self pollination/fertilization– Asexual reproduction

• Apomixis: parthenogenesis in animals and apogamy in plants

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Agents of Evolutionary Change• Nonrandom Mating: mating between specific

genotypes shifts genotype frequencies• Ladies, would you prefer to mate and produce

offspring with one of these males over another? If so, you are practicing non-random mating based on phenotypic characteristics

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Agents of Evolutionary Change• Nonrandom Mating: mating between specific

genotypes shifts genotype and phenotype frequencies– Assortative Mating: does not change frequency of individual

alleles; increases the proportion of homozygous individuals– Disassortative Mating: phenotypically different individuals

mate; produces an excess of heterozygotes

Less Genetic Diversity Hardy-Weinberg More Genetic DiversityMore Homozygotes Equilibrium More HeterozygotesClones/Clonal Lineages Many GenotypesMore Uniformly Fit Individuals Individuals of Varying FitnessLess Potential to Adapt to Change More Potential to Adapt to Change

Assortative Mating Disassortative MatingSelfing Inbreeding Random Mating Obligate Outcrossing

Inbreeding

• Mating between relatives or selfing in plants– Inevitable in smaller populations– Occurs in nature because of proximity of relatives –

example: natural stands of tree whose relatives are nearby because of limited seed dispersion

• If there is no natural selection, an inbreeding population will acquire an increase in the frequency of homozygotes without a change in allele frequency in the population

Coefficient of Inbreeding

Isonymy: having the same surname from both parents, an estimate of inbreeding in population records, e.g., birth certificates

Coefficient of Inbreeding

Three of Darwin's 10 children died in childhood, while another three never had any children of their own, despite being married for years

10 children

Agents of Evolutionary Change

• Mutation: Changes in a cell’s DNA

– Mutation is the ultimate source of genetic variation

– Since a new mutation transforms an allele into a different allele, it must also change allele frequencies

– Mutation rates are generally so low that they have little effect on Hardy-Weinberg proportions of common alleles in the short term, over a few hundred generations

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Agents of Evolutionary Change

Variation from1/10000 to

1/1000000000

Agents of Evolutionary Change

• Mutation: Changes in a cell’s DNA– Mutations are usually deleterious

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Stumpy, born 2007, in UK, on a duck farm, who eventually lost the two extra legs to accidental traumas, and his companion, Alice

Stumpy

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Agents of Evolutionary Change• Natural selection: environmental conditions

determine which individuals in a population produce the most offspring

• Three conditions are required for natural selection to occur:– Variation must exist among individuals in a

population– Variation among individuals must result in differences

in the number of offspring surviving – Variation must be genetically inherited

• We will return to natural selection in Chapter 15

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Agents of Evolutionary Change• Gene Flow: A movement of alleles from one

population to another– Migration of individuals or gametes between

populations– Migration can be a powerful agent for evolutionary

change– Migration tends to homogenize allele frequencies

between populations– But migration is adding or removing alleles from

the gene pool, so migration is going to change gene frequencies in the populations experiencing immigration or emigration

Agents of Evolutionary Change

• If enough migration occurs, the original isolates, with their inherent limited genetic variability, may fuse and form a new larger population with increased genetic variability.

Migration – the movement of breeding individuals into or out of isolated populations – results in evolutionary change because alleles move with the individuals. We call this movement gene flow.

Hardy-Weinberg Equation• Relates allele and genotype frequencies under

certain conditions• p2 + 2pq

+ q2 = 1• p = frequency of the dominant allele• q = frequency of the recessive allele

– The genotype frequencies of a population are– p2 is frequency of homozygous dominant genotype– 2pq is frequency of heterozygous genotype– q2 is frequency of homozygous recessive genotype

Sickle-Cell Anemia• In sickle-cell anemia, hemoglobin (Hbs) has poor oxygen affinity• Sequencing of the hemoglobin gene revealed one change from

the normal amino acid sequence:

Sickle Cell Anemia

Genotypes

Normal globin gene (H)

Sickle cell gene (h)

GAG (glutamate)

GTG (valine)

Hh Hh HhHH hh

Alleles

Phenotypes

Sickle-Cell AnemiaEvolution of populations is best understood

in terms of frequencies:1. Phenotypes 2. Alleles 3. Genotypes

Phenotypes Gene Alleles Genotypes

Normal hemoglobin

hemoglobin H HH, Hh

Sickle Cell hemoglobin h hh

Phenotype # people PhenotypeFreq.

Normal Homozygous Dominants & Carriers

29.94M 0.998

Sickle Cell Disease

Recessive 0.06M 0.002

Total # African Americans

30M 1.000

Actual Phenotype Frequencies: Sickle Cell Anemia in the African American Population

Sickle-Cell Anemia

Phenotype Genotype # People Genotypefreq

Dominant HH 27.4M 0.915

Dominant Hh 2.5M 0.083

Recessive hh 0.06M 0.002

Total # African Americans

30M

Actual Genotype Frequencies: Sickle Cell Anemia in the African American Population

Sickle-Cell Anemia

Genotype H-W ExpectedPhenotypeFrequency

Actual PhenotypeFrequency

Allele Allele Freq

HH 0.996004 0.915 ↓ H 0.998

Hh 0.003992 0.083 ↑

hh 0.000004 0.002 ↑ h 0.002

H-W Expected Frequencies: Sickle Cell Anemia in the African American Population

If p (0.998) + q (0.002) = 1

Sickle-Cell Anemia

Hardy–Weinberg Principle

• According to the Hardy–Weinberg principle, in a population of randomly mating individuals, allele frequencies are conserved and in equilibrium unless external forces act on them

• What is going on with Sickle Cell Anemia in African-Americans?

• [~400 years is only 16 human generations or so]

Figure 07: Hardy–Weinberg equilibrium

Adapted from Falconer, D. S. and T. F. C Mackay. Introduction to Quantitative Genetics, Fourth edition. Longman, 1996.

Sickle-Cell Anemia1. Is the population size is very

large?2. Is random mating is

occurring?3. Is mutation significant (over

20-30 generations since slave importation began)?

4. Is selection occurring?5. Are alleles transferring in or

out of the population (migration)?

1. Yes! 30M

2. Yes, as far as HgS is concerned

3. No [estimated at 5x10-8]

4. Yes; but against homozygotes

5. Yes, from African populations with a higher incidence of HgS

Sickle-Cell Anemia’sHeterozygote Advantage

• The recessive sickle-cell allele produces hemoglobin with reduced capacity to carry oxygen

• This mutation also confers malaria resistance in heterozygotes

• This heterozygote advantage leads to a larger proportion of the recessive allele than usual in areas where malaria is widespread

• These populations exhibit balanced polymorphism between the mutant and wild-type alleles

1. The population size is very large2. Random mating is occurring3. No mutation occurs4. No selection occurs5. No alleles transfer in or out of the population (no migration)

The Hardy-Weinberg Equilibrium

A population in true Hardy-Weinberg equilibriumis rarely seen in nature!

If a population meets all the assumptions of the Hardy-Weinberg Principle, then allele frequencies in the population will remain constant through future

generations

Additional Sources of Variation in Populations

• The extent to which a population departs from an optimal genetic constitution is called its genetic load, and is marked by the loss of some individuals through genetic death

• However, the presence of genetic variability in a population can be considered a sort of “insurance policy” for sexually reproducing species (and HGT is similar for asexual species)

Additional Sources of Variation in Populations

• On the other hand, there is, potentially, a major cost to the less fit in the variable/polymorphic population

• In technologically advanced societies, we are actually increasing the genetic load with modern medicine and pharmacology:– Diabetes mellitus– Atherosclerosis– Respiratory diseases– Susceptibility to a variety of microbial pathogens– Etc.

Populations, Allele Frequencies and the Gene Pool

• A population defined as a group of sexually interbreeding or potentially interbreeding individuals

• A deme is a locally interbreeding subset of the population

• The deme is most often the focal point for evolutionary change

• Consider the California yarrow, Achillea borealis and A. lanulosa

Figure B01B: A. borealis

© Sergey Chushkin/ ShutterStock, Inc.

Figure B01C: A. lanulosa

© Brzostowska/ ShutterStock, Inc.

Figure B01A: Locations of the populations and indication of genetic differences that have evolved

Adapted from Clausen, J. D., D. Keck, and W. M. Hiesey, Carnegie Inst. Wash. Publ., No. 581, 1948: 1–219.

Demes Can Adapt to Local ConditionsAverage height, timing and length of growing season, temperature and drought tolerance

varied among the populations on an east-west transect

Figure B02: Responses of clones from representative of the common yarrow

Adapted from Clausen, J. D., D. Keck, and W. M. Hiesey, Carnegie Inst. Wash. Publ. No. 581, 1–219.

Demes Have Different Gene Pools• Individual yarrow plants were

drawn from five different locales, shoots were cut and grown vegetatively into mature individuals

• These clones of individuals were then planted at different locations

• They showed considerable differences in fitness; some even dying in a different locale

Gene Flow / Gene Migration• At least three factors have an impact on the recipient

population:1. the difference in gene frequencies between the two

populations;2. the proportion of migrating genes incorporated into each

generation and its gene pool; and3. the pattern of gene flow, whether occurring once or

continually over time– Gene flow can hinder local evolutionary changes by

infusing genes from distant populations that are not so well adapted to local conditions

– Example: global blood group gene frequencies

Global Blood Group Gene FrequenciesThe original colonists of North America were a small group of apparently O+ founders; Caucasian Type A individuals may have originated in Scandinavia; Type B individuals seem to have originated in Central Asia

Different ABO blood group phenotypes may have little to do with variation in O2 transport, but are correlated with other factors such as disease susceptibility, e.g., Type A individuals seem to be less resistant to smallpox

O

BA

Selection, Variation and Increased Fitness

• R. A. Fisher, one of the founders of population genetics noted that the greater the genetic variation upon which selection for fitness may act, the greater the expected improvement in fitness

• Variation itself is subject to selection, and so the propensity to vary (variability) is an important attribute of organisms

Phylogeography• One tool for reconstructing the geographical

history of a lineage uses knowledge of genetics to plot variation in allele frequencies on the distribution map of the demes or populations of a species

Distribution of Mycobacterium tuberculosis strains in human populations

Phylogeography

• Another example: the spread of wheat– Strains of the Asian common wheat, Triticum

aestivu, reflect adaptations of a single species to a large number of environments

Adapted from Ghimire, S. K., Y. Akashi, C. Maitani, M. Nakanishi and K. Kato, Breeding Sci., 55 (2005): 75-185.

Figure 09: Asian common wheat Figure 10: Asian common wheatAdapted from Ghimire, S. K., Y. Akashi, C. Maitani, M. Nakanishi and K. Kato, Breeding Sci., 55 (2005): 75-185.

The pie charts record frequencies of two isozyme

alleles, probably the tan representing a more cold

and drought resilient form than the brown

Why Doesn’t Natural Selection Eliminate All Genetic Variation in Populations?

• Natural selection tends to reduce variability in populations by eliminating less fit alleles

• Mechanisms which counteract that elimination to preserve genetic variation include:– The diploid condition preserves variation by “hiding”

recessive alleles (Bb)– Balanced polymorphisms (2 or more phenotypes are

stable in the population) may result from: 1. heterozygote advantage: Aa superior to aa and AA 2. frequency-dependent selection 3. variation within the environment for a population

Frequency-Dependent Selection• Frequency-dependent selection is the term given to an evolutionary

process where the fitness of a phenotype is dependent on its frequency relative to other phenotypes in a given population

• In positive frequency-dependent selection, the fitness of a phenotype increases as it becomes more common

• In negative frequency-dependent selection, the fitness of a phenotype increases as it becomes rarer (this is an example of balancing selection)

• Frequency-dependent selection is usually the result of interactions between species (predation, parasitism, or competition) or between genotypes within species (usually competitive or symbiotic), and has been especially frequently discussed with relation to anti-predator adaptations

negative frequency-dependent selection in fruit flies

Chapter 13

End

Genetic Polymorphism