exam 2 evolutionary

What are the sources of genetic variation?

• Point mutations

• Recombination during crossing over

• Segregation and independent assortment

• Transposable elements

• Chromosomal Fusion-Fission

• Polyploidy

what are the various types of point mutations?

• DNA synthesis and repair

• Silent

• Missense

• Sense

• Nonsense

• Frameshift

SIlent Point Mutations

• Not affecting primary structure of polypeptide chain

• Change in nucleotide sequence that does not change the amino acid specified by a codon

Missense mutation

• One nucleotide is replaced by another

• Ex: Melanocortin 1 receptor

• Change a nucleotide sequence that changes the amino acid specified by codon

Nonsense mutation

• Change in nucleotide sequence that results in an early stop codon 

• Created protein that is shorter (from amino acid → stop codon)

• Ex: Cystic fibrosis

Sense mutation

Stop codon is converted into amino acid → elongated protein

• Hemoglobin Constant Spring → lengthening causes anemia

Frameshift mutations

• Nucleotide deletions or insertions

• Adding on extra nucleotide effects the frame and codon sequences

When do point mutations originate?

Point mutations originate during DNA replication or repair errors

Transitions vs. Transversion

Transitions: from one purine to another (adenine to guanine)

Transversion: from a purine to pyrimidine, vice versa

When do Trinucleotide repeats originate?

They arise during replication when DNA polymerase “slips”, expanding repeat regions. Gene expression or protein function is disrupted.

• Same sequence multiple times

• Premutation allele → 60-200 

• More than 230 → mutant allele

Which disorders are caused by Trinucleotide repeats?

• Fragile X syndrome: Severe cognitive dysfunction, harms boys because they only have 1 X chromosome

• Huntington’s disease: Unwanted movements, behavioral changes, paralysis, death

• Myotonic dystrophy: Muscle weakness, myotonia (delayed relaxation), cataracts, cardiac arrhythmias 

Which mutations originate during crossing over?

• Duplication → longer segment, prophase 1, meiosis 1. A piece of the chromosome is copied and inserted, while leaving the original piece in place

• Deletion

• Inversion → piece of chromosome is flipped upside down, reversing its direction

• Translocation → piece of chromosome moves to a different chromosome (that is unrelated), will be rearranged 

Explanation of Mutations that originate during crossing over

• Crossing over: 2 chromosomes line up perfectly

• Mispair → overlap chromatids → some chromosomes inherit 3 copies or 1 copy (not involved in equal exchange)

How do gene families originate?

Gene duplication, combining polypeptides

• Duplication creates an extra copy of a gene that accumulates mutations and evolve new functions while the original copy maintains its role

Example of a gene family

Globin gene loci in Humans and Mice

• Over evolutionary time, an ancestral globin gene duplicated many times, allowed for slightly different functions

• Hemoglobin different throughout life

• Embryonic HB → hae greater affinity for oxygen, good for extracting O2 from mom)

• Adult Hb → no more affinity 

Which mutations originate during segregation?

Errors in meiosis, such as nondisjunction, unequal segregation. Lead to aneuploidy or chromosomal abnormalities (monosomy, a missing chromosome or trisomy, an extra chromosome)

Recombination and Fertilization generate variation

Meiosis: when gametes for 2 homologous that exchange → create new combination of alleles

• Two distinct organisms mating, increase DNA variation

Independent assortment ensures novel combinations of alleles

• Way chromosomes segregate when gametes form

• more pairs, more variability in gametes (from 2 homologous pairs)

What are the various types of transposable elements?

DNA sequences that move to many places in the genome

• DNA transposons → Detach from original location, insert to another place in he genome (nonreplicative), enzyme cuts and inserts into new location

• Replicative DNA transposon → copied itself, inserted copy in other location of genome

• Retrotransposons → Move around genome using an RNA intermediate (complementary inserting itself somewhere else in the genome)

• First transcribed into RNA, reverse transcribed back into DNA by reverse transcriptase

• Inserted into new loc in genome

DNA transposons

• Detach from original location, insert to another place in he genome (nonreplicative), enzyme cuts and inserts into new location

• Replicative DNA transposon → copied itself, inserted copy in other location of genome

RNA transposons

Move around genome using an RNA intermediate (complementary inserting itself somewhere else in the genome)

• More potential to cause mutations

• First transcribed into RNA, reverse transcribed back into DNA by reverse transcriptase

• Inserted into new loc in genome

• Ex: LINE (reverse transcriptase) → long interspersed nuclear elements, code for retro transcriptase. Autonomous, independent

• SINE → short, interspersed nuclear elements 

What are the effects of transposition?

• Insertional mutagenesis → mutation caused by the insertion of foreign/mobile DNA into a gene, leading to disruption or misregulation of gene function

• Gene disruption

• Altered gene expression

• Genomic rearrangements 

How can we determine chromosomal fusion?

• Two chromosomes fusing into 1 chromosome, where there are extra centromeres and telomeres in the middle of the chromosome

• By comparing karyotypes and looking for shared telomere sequences or centromere remnants 

• Ex: human chromosome 2 originated by fusion of two ancestral ape chromosomes, has telomeres in the middle 

How does genetic variation arise in prokaryotes?

Through polyploidy (organisms that have 3+ copies of each chromosome)

• Mutation, horizontal gene transfer (transformation, transduction and conjugation)

Population genetics 

study of allele frequencies and changes in allele frequencies in a population (in a particular population, genotypes)

What are the assumptions of the Hardy-Weinberg Equilibrium?

• Population is infinitely large

• No selection

• There is no mutation (no net mutation)

• Mating is random

• There is no migration (no net migration → population leaving = population entering)

What are the predictions of Hardy Weinberg about allelic and genotypic frequencies?

Allelic and genotype frequencies remain constant over generations in the absence of evolutionary forces (mutation, selection, migration and drift)

• Allele frequencies predict genotypic frequencies

• Reject null hypothesis if we do not see what is expected by Hardy Weinberg

What is heterozygote advantage?

Heterozygotes that have higher fitness than either homozygote (overdominance)

Ex: Sickle cell heterozygotes (HbA/HbS) resist malaria infection

What accounts for the high frequency of thalssemia carriers in countries around the Mediterranean and in Southeast Asia?

Resistance to malaria

• Infected red blood cells tend to sickle (more likely to rupture, cleared out by spleen more effectively) 

• Clears out old and nonfunctional RBC

• Red blood cells produce more superoxide anion (O2-) and hydrogen peroxide (H2O2) toxic to pathogens 

• Reactive hydrogen species, more effectively kill pathogens 

Which of the following statements is untrue about gene duplications?

They occur during DNA replication

Point mutations occur during

DNA replication

Which evolutionary mechanism can lead to adaptation?

Natural selection

Which evolutionary mechanism can increase genetic variability of a population?

Migration

Insecticide Resistance in C. Pipiens

• Increase production of enzyme that breaks down insecticide

• Overproduce enzyme → resistance

Pleiotropy

mutation in a single gene affects many phenotypic traits

• Net effect on fitness determines outcome of selection'

• Increase resistance to pesticide 

• Increased susceptibility to predation 

• Low productive success in males

Increased fitness in E.coli

• Unique events occur for each population of E. Coli

• Those who arrive at 50k generations exhibit improved fitness, although they do not end up at the same point

Negative selection

Alleles that lower fitness experience are eliminated

Positive selection

Alleles that increase fitness

What is genetic drift?

Random change in allele frequencies due to chance, strongest in small populations

• Sampling error

• When sample is too small, is not representative of population in bowl

• Sample error is higher with a smaller sample

What populations are primarily affected by genetic drift?

Observed best in small populations, where some alleles are being lost and some become very common (rapid fixation)

Ex: Genetic drift in D. Melanogaster

• over time, more and more populations lose a allele and become fixed for either bw or bw75

• bw75 was lost, both reached fixation

What is the bottleneck effect?

A population undergoes a drastic reduction in size; survivors’ alleles dominate future generations

Ex: Northern elephant seal

• Subject to hunting

• N = 30 survivors, mtDNA, 2 polymorphisms (2 specific loci in the same stretch of DNA)

• Reduce number of individuals that reproduce

Allele loss probability in Bottlenecks

• p = 0.01 → allele is rare, more likely to be lost

• p = 0.10 → common

• Smaller population, more probability on allele will be lost

Haplotype

• Several genetic markers located on same chromosome

• Population can have several haplotypes

Polymorphism

Specific locus in same stretch of DNA

• Variation in one locus

What is founder’s effect?

When a few individuals colonize a new area, they carry only a fraction of total genetic variation

• Colonizing a new environment (areas that are isolated and lack their species 

• New populations started by a small number of individuals

• Founder effect causes genetic drift 

• Ex: Black spruce expansion, forest expands (more north reduced)

Founder effect → Mutiny on the Bounty

Background: British ship crew rebelled against captain, took captain and pushed out to sea

• Lead to the colonization of Pitcairn (1789)

  → 11 mutineers, 6 Tahitian women

• As population increased, they moved to a new island, Norfolk (1854)

• 193 colonists → population 2,000 (today)

Which evolutionary sources lead to adaptation?

Natural selection and mutation (raw variation)

What are the effects of genetic drift and gene flow?

Drift: decreases variation, causes random fixation/loss of alleles

Gene flow: increases genetic variation, but disrupts local adaptability

• Causes allele frequencies to be more alike (in two populations)

What are the differences between Mendelian vs. quantitative traits?

Mendelian traits: monogenic or discrete (single gene)

Quantitative traits: continuous, polygenic traits influenced by environment (influenced by many genetic loci, 4 genes for 1 trait)

What are multifactorial traits?

Heritability (construct that estimates genetic variance to environmental variance)

• Traits influenced by multiple genes and environmental factors 

What is heritability?

Statistical construct that estimates the amount of variation that is attributed to genes

• Applies to a specific population in a specific environment

• Explains the variance among individuals, not the character itself

• Ex: height heritability

Example of heritability

• Ex: Height heritability

• 0.8 → variance b/c of genetic makeup (additive effects of recessive alleles, dominant alleles, epistasis (one gene influencing expression of another gene)

• 0.2 → b/c of environmental factors 

What is absolute genetic determinism?

Traits entirely determined by genotype with no environmental influence (Ex: blood type → only genes that affect the blood type)

How does Broad Sense heritability differ from Narrow Sense Heritability?

Broad sense (H²): includes all genetic variance (additive, dominance, interaction): H² = VG / (VG+ VE)

Narrow sense (h²): includes ONLY additive variance → h² = VA / (VG + VE)

Broad sense (H²) equation

H² = VG / (VG+ VE)

Narrow sense (h²) equation

h² = VA / (VG + VE)

Breeder’s equation

R = h² x S

• R = response to selection

• h² = heritability

• S = selection differential

What are the various types of natural selection?

• Directional 

• Stabilizing

• Disruptive 

• Balancing

Directional selection

One extreme phenotype has advantage (selected for)

Ex: Elephant tusklessness (females)

• In early 70s → only 18.5% of females were missing tusks

• 1977-1992 → War rebels killed elephants and sold tusks for armor

• Strong selective pressure, one extreme was selected → 50.9% missing tusks

• Number (as of most recent) has shifted to 58.4% having tusks

Stabilizing selection

Average phenotype has advantage

Example: Aposematic coloration stability

• Warning color for predators (prey is nonpalatable)

• Tested reflectiveness of yellow and red on body as there is variation in spots and color

• Limited variation between sites

• Some variation (reflective on red), limited variation (reflective of yellow)

• Constant average was associating yellow with unpalatable food (predators)

Disruptive selection

Two extremes → advantage

• Average → disadvantage

• Pushing population to 2 extremes

• Bimodel distribution

• Example: Color morphs in stick insects 

Example of disruptive selection in stick insects

• Polymorphic (T. Chumash), also has intermediate and melanic → greater variability in host plant colors

• T. Bartmani → have green and brown → melanic morphs (match host plant leave and twig colors)

• T. Cristinae → green and brown - mostly match green leaves and brown twigs

• Mark insects, see how many return after capture (T. Chumash)

• 40 of each in each treatment (green, intermediate and melanic)

• In treatment with host plants of other 2 insects, two species show disruptive selection (2 extremes)

Balancing selection

Multiple alleles are being maintained (polymorphism) → different alleles

• Heterozygote advantage → sickle cell anemia, at an advantage where malaria is

• Negative frequency dependent selection → when allele is rare, selected for (higher fitness)

• Fluctuating selection → when rare allele is selected, it becomes common, common allele is blocked

Example of fluctuating selection (T. cristinae)/Balancing selection

Three morphs of unstriped, striped, melanistic

• one morph: green, striped (frequency is high) → becomes low → returns high

Visual predators → create search image for high frequency morph (rare) → becomes common, predators hunt for this search image

Strong vs. Weak selection for Body size 

Usually goes for strength of selection → area between mean size of entire pop. and mean size of reproducing individuals

h² = 0

Heritability of 0 → not passed on, no genetic contribution

• population will remain consistent

• R → response

h² = 1

R = S → response equals strength of selection

Which factors affect the degree to which a population will evolve?

• Heritability

• Strength of selection

• Mutation

• Gene flow

• Drift 

What is linkage disequilibrium?

Alleles on same chromosome

• Loci that are adjacent to each other are tightly physically linked, inherited together 

How do genetic markers work?

• BRCA1 gene → tumor suppressor

• Linkage disequilibrium with all loci along the entire chromosome → mutation of BRCA1 increases risk of breast cancer → disables gene

• Recombination occurs → crossing over during meiosis

• After 4 generations, linkage disequilibrium remains (decreases in size), SNPs tightly physically linked with a disease risk allele can be used as a genetic marker for the presence of this allele

What are SNPs?

Single Nucleotide polymorphisms

Linked SNPs 

• outside of gene → no effect on protein production or function → can indicate where gene is located

non coding SNPs

changes amount of protein produced

coding SNP

changes amino acid sequence

Causative SNPs

in gene

• non coding SNP → changes amount of protein produced

• Coding SNP → changes amino acid sequence

What are Variable Number Tandem Repeats?

Variable number tandem repeats (DNA sequences)

• varies for each individual

• basis for genetic fingerprinting

What are the various applications of LD?

• Estimate mutation origin → size of link. diseq→ big in new population, small in old population

• QTL analysis

• GWAS→ genes under selection, selection effects, gene identification

• Indicator of positive selection

• Test historical hypotheses → Ex: Did Polynesian travel to South America? → took ancestral DNA and modern DNA → short around SA markers (recent), large with ancestral DNA

How is QTL analysis done?

Statistical association of genetic markers with phenotypic variation in controlled crosses; typicaly uses LOD ≥ 3 as significant

• Breed largest individuals tg. And smallest individuals to create 2 homozygous

• Generations will be heterozygous

• Observe high likelihood ratio (marker and trait association)

• Where genes related to characteristics are used → if parallel, they are inherited tg.

QTL analysis of coat color in mice

• Beach mouse

• Mainland

• 1st gen hybrid → created

• 2nd gen → heterozygous for every loci

• Some will be light, some will be dark

• F2 = 465 → polygenic mutation , multiple genes

Interaction of Agouti and MC1r 

• Agouti (gene) → Mc1r inhibits (if there is a missense)

• If there is high signaling, dark pigment is expressed

• Low signaling (has a missense), no pigment is expressed

• MSH (melanocyte stimulating hormone) → bonds to receptor (Mc1r)

Epistasis 

• Interaction between genes where one gene masks or modifies the effect of another on the phenotype (can effect trait heritability and selection responses)

• Mice → DD at the agouti locus, Mc1r has no effect on the phenotype

• DL OR LL → at Agouti locus, the alleles at the Mc1r locus influence phenotype (important for coloration)

Which alleles are involved in phenotypic expression?

More dark pigment on the dorsal (back) → more dark fur

No pigment on ventral belly → less dark pigment expressed → bicolor beach mice, greater degree of Agouti

Precise mechanism of Agouti

• Is responsible for maturation of melanin

• Delays melanocyte maturation

• Strongest ventral expression (side of belly)

Non-Agouti peromyscus

• Experienced gene deletion, cannot be expressed

• Is fully dark, hair follicle has no color because of Agouti (when expressed) → inhibits color of melanin (have MLV + Agouti)

• Control → no working Agouti → melanocytes developed hormonally (just MLV)

Genetically manipulated dark mice

• Are homozygous for Agouti allele LL

• Shows ratio of expression

• Intermediate from dorsal midline

What is the significance level in QTL studies?

LOD ≥ 3 as significant

What are GWAS?

Genome Wide Association Studies

• Genetic markers for diseases (SNP-trait associations in populations)

• Looking at entire genome → limited to organisms where several genomes have been sequenced (Model organisms)

• Ex: patients with coronary artery disease and those who do not

• p < 5 × 10^8 = -7.3

• -log (0.00000005) = 7.3 → any marker under 7.3 is insignificant

What is the significance level in GWAS studies?

p < 5 × 10^-8

What is phenotypic plasticity?

Expression of gene influenced by environmental factors

• 1 genotype can generate many phenotypes in environment

• Shows norm of reaction

• Ex: low light vs high light

Example of plastic plasticity 1

• Low biomass with low light environment, bigger leaves are produced (photosynthesis need increases due to lack of light) → produces more chlorofilm

• High biomass with high light environment (smaller leaves, receives sufficient amount of photosynthesis)

Norm of reaction

Set of phenotypes produced by genotype

What is Polyphenism?

Discrete environmentally induced phenotypes

Ex: How many nutrients are present?

• On beetles, low nutrients causes no horns

• High nutrients, male has horns 

How can we detect genotype environment interactions?

By measuring phenotypic responses across multiple environments and comparing reaction norms

What is gene coalescence?

Tracing alleles in a population back to a common ancestral copy (most recent common ancestor)

How can gene trees differ from species trees?

• Gene trees trace the ancestry of a particular gene

• Species trees trace the ancestry of an entire species

• Incomplete lineage sorting or gene duplication → causes gene trees to not always match species trees 

What is a molecular clock?

Assumes mutations accumulate at a roughly constant rate, allowing estimation of divergence times

Which areas of the genome evolve faster/slower?

Faster: noncoding, pseudogenes, synonymous sites

Slower: essential genes under strong functional constraint

What is Maximum Parsimony?

Tree with fewest character changes

• Creating phylogenetic tree with lowest number of changes 

What is bootstrapping and how is it used in the construction of phylogenetic trees?

Bootstrapping: testing tree robustness using character subsets. Statistical resampling of data to test the robustness of tree nodes. Higher bootstrap values indicate stronger support

• Originally 4 species, 10 characters

• Using those with the highest confidence (100)

What is the method of neighbor joining?

Joining species that have the fewest differences together (clustering taxa by minimizing total branch lengths)