Test 2
Polygenetic traits
inherited multifactorially and Mendelian multifactorial inheritance models are (much) more complicated than simple (single locus) mendelian models
In-frame mutation
insertion mutation an insertion of deletion that shifts the reading frame by a multiple of three nucleotides
Frameshift mutation
insertion mutation insertion of deletion that shift the reading frame by multiple less than 3
Inbreeding
mating with a close relative eliminates heterozygotes from a population
Disassortative mating
mating with individuals of different genotypes or phenotypes (MHC loci) Non-random mating produces an excess of heterozygotes relative to populations in HWE. The outcome can be similar to a balanced polymorphism.
Assortative mating
mating with individuals of the same or similar genotypes or phenotypes Example: Hemophilia (recessive, sex-linked disorder)
Eukaryotic cells contain organelles which have their own genome:
mitochondria, chloroplast, nucleus, etc.
Molecular clock
neutral theory can be used to suppose the idea that selectively neutral mutations arise a similar rates in different taxa and are fixed at similar rates and all of this is independent of demographic parameters
Linkage disequilibrium
non-random associations between alleles at multiple loci
Genetic drift
the process of random fluctuation in allele frequencies due to sampling effects (can be really bad)
Effective population size
the size of an idealized population that loses genetic variation due to genetic drift at the same rate as the population under study
Codons
three-base sequences that specify amino acids when translating RNA to proteins
Gene
total extent of DNA that specifies a functional product
Why is mutation is important to with germ-line and somatic cells?
germ-line (sex cells) mutations go to offspring somatic (body) mutations do not go to offspring (like UV)
Why is the Hardy Weinberg Model important?
"Null" model which establishes what occurs to allele frequencies in the absence of evolutionary forces (we can compare our observations to these predictions) Frequencies of A1 and A2 do not change in absence of evolutionary processes If we know allele frequencies, and if mating is random, we can predict equilibrium genotype frequencies In absence of evolutionary processes, loci will go to Hardy-Weinberg equilibrium in a single generation
DNA
-Deoxyribonucleic acid, double stranded, composed of 4 nucleotides -Adenine and guanine... purines 5 and 6 sided ring -Cytosine and thymine... pyrimidines only 6 sided ring -Hydrogen bonds, Strands are anti parallel, nucleotides are complementary -DNA is wrapped around nucleosomes which are composed of histones -Nucleosomes are then packed into chromatin -Chromosomes are packed/ condensed chromatin -Chromosome number varies by taxon -The amount of DNA in organisms also varies
Consequences of genetic drift
1. Allele frequencies fluctuate over time even in absence of natural selection depending on populations size. A random allele with either be fixated or lost. 2. Some alleles are fixed, some are lost, and heterozygosity decreases over time. When alleles are fixated or lost, variation is lost. 3. By chance, populations diverge in their allele frequencies over time creating diverging species.
Criticism of Mendel
1. Mendel's traits were discrete while most traits seem continuous 2. Unclear whether Mendel's ideas were consistent with Darwin's theory of evolution by natural selection 3. For discrete traits, Mendelian frequencies did not seem correct...
Evolutionary change at the sequence level (natural theory of molecular evolution)
1. Most molecular variation present in a population is selectively neutral 2. Most of the changes to DNA overtime are also selectively neutral -Because most changes are selectively neutral, when DNA sequences changes over time, some process other than selection must be the cause provides a mathematical model that we can use to make predictions about the variation we expect in a population, the rates of synonymous substitutions, the rates of non-synonymous substitutions, and several other population genetic parameters in population operating outside of selective pressure
Hardy Weinberg Assumptions
1. Natural Selection is not operating on a trait affected by locus 2. Mating in random with respect to locus 3. No mutation 4. No migration (into or out of population) Population is effectively infinite in size
How are molecular changes selectively neutral?
1. Synonymous substitutions: many molecular changes do not change phenotypes - degenerate code allows changes to DNA sequence that do not translate to proteins 2. Non-synonymous substitutions may have little effect: (substitutions that change an amino acid) may still have few effects → Slightly changing a protein sequence cause little or no effect 3. Variation in untranslated regions: human genome is ~3 Gbg in size, roughly 2% is translated (60,000,000 bp), roughly 98% is untranslated, and mutations likely have minor effects 4. Effective neutrality: natural selection operates weakly on mutation with small effect and random changes in allele frequency due to drift swamp effect of selection so alternate alleles/mutations of small effect are affectively neutral
Reginald Punnet
Argued that Brachydactly (among others) was dominant Mendelian trait (he was correct) which he was correct, BB and Bb have brachydactly and bb does not
G. Udny Yule
Argued that dominant traits occur at 3:1 and should occur in most humans but Barchydactly is very rare in humans Thus, Brachydactly was not Mendelian And, Mendelian traits did not exist (he was incorrect)
How does natural selection change the frequencies of the dominant and recessive allele in the population?
As selection gets stronger (s increases), allele frequencies (p) change faster and f[A1] approaches fixation earlier
Law of Large Numbers
As the size of a random sample of a population increases, the sample frequencies we observe are close to the actual frequencies we observe are close to the actual frequencies in the population
Motoo Kimura
Suggested selection is not acting on all of the variation, at all... so natural selection acts strongly on phenotypes, but perhaps not so strongly at the molecular level Founded Natural Theory of Molecular Evolution
Example of Hardy Weinberg Problem: EphB2 is associated with head crest phenotype
Assume it is a single autosomal locus that is a recessive trait 100,000 pigeons in population 1,000 pigeons are heterozygous 1,700 have reversed head crest feathers How many pigeons will have reversed head crest in F2 generation? 1700/100000= 0.017, 1000/100000= 0.1, 97300/100000= 0.973 A1 = 0.973+ 0.01/2= 0.978 A2= 0.017+ 0.01/2 = 0.022 1= p2 + 2pq +q2 1= 0.956 + 0.044 + 0.0005 Q2= 0.0005*100,000 is 50 pigeons If q was dominant: 0.044*100,000 + 50 pigeons = 4450 pigeons
A change in allele frequency at one locus does not result in the change in allele frequency at a second locus. These loci are most likely: Select one: a. linked b. recessive c. dominant d. unlinked
d. unlinked
How is DNA made functional?
DNA --> trans --> pre-mRNA --> splicing --> mRNA --> translation --> protein
Hardy Weinberg
Developed a mathematical model to predict the population-level consequences of Mendelian inheritance 1. Model allowed Hardy to refute claims of Yule regarding Brachydactly in 3:1 ratio, supporting Mendelian inheritance; to show that dominance of a trait had nothing to do with it's transmission (in absence of selection) Established the idea of population-level thinking (or population-genetics) Effectively established a quantitative or numerical perspective on evolutionary change
What controls transcription?
Enhances: regulatory elements that increase the rate of transcription Silencers: regulatory elements that decrease the rate of transcription Cis regulatory elements: affect genes at nearby sites on same chromosome Trans regulatory elements: affect genes on other chromosomes
Hardy Weinberg Model
Establishes what will happen over time to allele frequencies in the absence of evolutionary processes
A population bottleneck occurs when a small number of individuals from a large population colonize a new area. Select one: True False
False
The C-value paradox states that "despite the seemingly large differences in organismal complexity, multicellular eukaryotes tend to have similar numbers of protein coding genes". Select one: True False
False
The law of segregation states that the allele passed down to the next generation at one locus is independent of which allele is passed down to the next generation at another locus. Select one: True False
False
Affect of migration on Hardy Weinberg
Flow of migrants between populations can change the allele frequency of each. 1. When individuals immigrate to a population → May bring new or uncommon ancestors 2. When individuals emigrate from a population → If emigrants are more likely to leave, may affect allele frequency
Hardy Weinberg Principle
In a quantitative sense, evolutionary change occurs when genotype frequencies change over time.
Who discovered DNA?
James Watson, Francis Crick, and Rosalind Franklin
How does new variation arise?
Natural selection is reducing variation Polygenic traits can generate massive numbers of combos -Two alleles at 10 loci 60000 possible genotypes New phenotypes could be due to the re-assortment of genotypes Selection/drift can draw out new phenotypes/genotypes from all combinations So polygenic traits in populations can contain latent variation—not all possible genotypes are represented until selection/drift draw them out
Wright-Fisher Model
Small population version of Hardy-Weinberg Identified a quantitative measure of allele frequency changes in small populations
Different parts of the genome evolve at different speeds (or "rates"). Select one: True False
True
Herman Nilsson-Ehle determined that the presence of only two variants (AKA alleles) at each of 10 different loci was sufficient to generate as many as 60,000 phenotypes. Select one: True False
True
If a base substitution creates a stop codon where there was not one previously, this is known as a nonsense mutation. Select one: True False
True
Linkage disequilibrium, or the statistical association between alleles at two loci, can arise due to both the physical distance between two loci on a chromosome and genetic drift. Select one: True False
True
The Hardy-Weinberg equilibrium is effectively a null model - meaning that it tells us what we can expect when natural selection (and other drivers of evolutionary change) are not operating. Select one: True False
True
Recombination
Why sexual reproduction is beneficial, sex helps purge deleterious mutations through recombination, reverses Muller's Ratchet Crossing-over: physical exchange of DNA segments between homologous chromosomes
If loci are on the same chromosome, the segregate...
dependently. When this happens, we say there is physical linkage between the two loci. In absence of recombination, physically linked loci segregate together, so an AB|ab parent will produce only AB and ab gametes.
Population bottleneck
a brief period of small population size that can drastically alter allele frequency causes populations to diverge
Mutation
a change to the DNA sequence of an organism that is the ultimate source of genetic variation can be beneficial, deleterious, or neutral variants and random changes of a trait or DNA that increases the survival and reproductive success of an individual
Genetic drift is best described as: Select one: a. A random process b. A non-random process c. A finite process d. A selective process
a. A random process
This individual believed that any dominant, Mendelian trait should occur in a 3:1 ratio. Select one: a. G. Udny Yule b. G. H. Hardy c. Reginal Punnett d. Gregor Mendel
a. G. Udny Yule
Loci on different chromosomes segregate: a. Independently b. Dependently
a. Independently
Which of the following is not one of the Hardy-Weinberg model assumptions? Select one: a. There is migration into or out of the population b. Mutation is not occurring c. Natural selection is not operating on the trait or traits at the locus in question d. Mating is random e. Population is effectively infinite in size
a. There is migration into or out of the population
Genetic drift causes changes in: Select one: a. allele frequencies b. population size c. The strength of natural selection d. the genetic code
a. allele frequencies
Spliceosome
an RNA + protein complex that removes introns and splices together exons to form a mRNA strand
Phenotype
an organisms observable, physical, developmental and behavioral characteristics affected by proteins interacting with the environment *For natural selection to operate, genetic information in the DNA must affect the organism's phenotype.
Consider a population with two loci (A, B), each with two alleles (A, a ; B, b). What are the allele frequencies in this population if the haplotype frequencies are AB = 0.35, Ab = 0.15, aB = 0.35, ab = 0.15? Select one: a. A = 0.6, a = 0.4, B = 0.7, b = 0.3 b. A = 0.5, a = 0.5, B = 0.7, b = 0.3 c. A = 0.7, a = 0.3, B = 0.5, b = 0.5 d.A = 0.5, a = 0.5, B = 0.6, b = 0.4
b. A = 0.5, a = 0.5, B = 0.7, b = 0.3
When an unselected or possibly disadvantageous allele changes in frequency because of it's degree of linkage disequilibrium with another allele that is under selection, it is called: Select one: a. Artificial selection b. Genetic hitchhiking c. Natural selection d. Background selection
b. Genetic hitchhiking
Antibiotic resistance is best described as an example of: Select one: a. Purifying selection b. Periodic selection c. Genetic hitchhiking d. Background selection
b. Periodic selection
Imagine an island archipelago where all of the islands are founded by individuals heterozygous at a particular locus. If there is no migration or mutation, and the alleles at that locus are neutral, what do you expect the island populations to look like after many generations? Select one: a. The populations on every island will have fixed the same allele b. Some island populations will have fixed one allele, and other populations will have fixed the other allele c. The island populations will have high levels of genetic diversity at this locus. d. We cannot predict any outcome because genetic drift is a random process
b. Some island populations will have fixed one allele, and other populations will have fixed the other allele
Eukaryotic genome size is: Select one: a. tightly correlated with organismal complexity. b. not well correlated with organismal complexity. c. typically smaller than prokaryotic genome size. d. approximately the same in all eukaryotes.
b. not well correlated with organismal complexity.
Consider a locus with only two alleles, A and a, in a population of diploid individuals. If the frequencies of A and a in the population are p and q, respectively, then p + q = Select one: a. 0.5 b. p*p c. 1.0 d. 2.0
c. 1.0
Which of the following statements regarding RNA versus DNA is true? Select one: a. Only RNA uses guanine b. Only RNA uses cytosine c. Only RNA uses uracil d. Only RNA uses adenine
c. Only RNA uses uracil
Viral genomes: Select one: a. consist only of RNA. b. are always found as a single circular chromosome. c. may consist of DNA or RNA. d. consist only of DNA.
c. may consist of DNA or RNA.
Selection coefficient (s)
describes the fitness reduction of one phenotype relative to another
We will talk about this more in class, but pigeons have a gene, EphB2, that controls head crest feather development. A recessive allele at this locus reverses the feathers on their head crests and basically makes them look like they have a huge cowlick. There are 100,000 pigeons in the population; 1,000 pigeons are heterozygous for the recessive trait; and 1,674 pigeons have reversed head-crest feathers. If we call the dominant allele A1 and the recessive allele A2, which of the following is closest to the frequency of the A2 allele? Select one: a. 0.973 b. 0.978 c. 0.017 d. 0.022
d. 0.022
The codon triplet ACC codes for the amino acid: Select one: a. Cysteine b. Arginine c. Leucine d. Threonine
d. Threonine
Bacteriophage MS2 was the first organism to have its entire genome sequenced, and this was facilitated by: Select one: a. the bacteriophage's long and complex genome. b. previous sequencing of bacterial genomes. c. the bacteriophage's role as a human pathogen. d. the bacteriophage's exceptionally small genome.
d. the bacteriophage's exceptionally small genome.
The C-value paradox is: Select one: a. unresolved due to the presence of noncoding DNA. b. the strong correlation between genome size and organismal complexity. c. resolved by the discovery of linkage disequilibrium. d. the lack of correlation between genome size and organismal complexity.
d. the lack of correlation between genome size and organismal complexity.
Mendel's First Law: Law of Segregation
each individual has two gene copies at each locus (the physical location of gene copies on the chromosome) and these gene copies segregate during gamete production, so that only one gene copy goes into each gamete
Molecular evolution
evolutionary change at the molecular/sequence level (versus the level of the phenotype)
Agouti vs Mc1R
example of epistasis homozygous dominant agouti masks all effects of Mc1R, heterozygous Agouti allows Mc1R to influence phenotype
Selfing
extreme form of inbreeding in which individual fertilize their own gametes (mostly plants and very few animals) eliminates heterozygotes from a population
Frequency independent selection
fitness associated with a trait is not directly dependent on the frequency of that trait in a population
JBS Haldane
formalized idea that single mutant allele will likely go to fixation with probability of 2*s (so 1 in 50 chance)
Mutations can occur at the gene or chromosomal level:
gene duplication: two copies of a gene chromosomal duplication: two copies of a chromosome chromosomal deletion: removes genes on chromosome chromosomal inversion: copies are moved around chromosomal translocation: genes move from one segment of chromosome to another part
Transcription
process when the sections of DNA are unwound, portions are copied into RNA and then translated into proteins occurs when a complementary and antiparallel strand of RNA is synthesized from a strand of DNA
What types of RNA is made from transcription?
rRNA (ribosomal RNA): component of ribosomes that are responsible for translation tRNA (transfer RNA): transports amino acids to ribosomes microRNA: plays role in gene regulation (post-transcription)
In the presence of _____, physically linked loci can be reassorted to form new allelic combinations.
recombination the rate of recombination depends on the physical distance between loci on the chromosome—recombination increases with distance
Where does new genetic variation come from?
recombination and mutation
Haplotypes
set of alleles, one at each locus under consideration
Causes of mutations:
spontaneous mutation (such as sun exposure) translesion synthesis DNA repair induced mutation (radioactivity)
Exon
stretches of DNA in a gene that code for protein product
Intron
stretches of DNA in a gene that do NOT code for protein products
Synonymous mutation
substitution mutation base substitution that does not change the amino acid encoded by the codon
Missense mutation
substitution mutation change in nucleotide that creates different amino acid encoded by the codon
Nonsense mutation
substitution mutation change in nucleotide that creates different amino acid which encodes for a premature stop codon
Transversion mutation
substitution mutation purine to pyrimidine or vice versa
Transition mutation
substitution mutation transition of purine to purine (A or G) or pyrimidine to pyrimidine (C or T)
Mendel did not know:
the actual biological mechanism for gene transmission (DNA/genome biology) or the factors maintaining inherited variation (mutation, recombination, etc)
Founder effect
the change in allele frequency that results when a small number of individuals from a large population colonize and found a new area
Census or population size
the count of individuals in population which fluctuates from generation to generation, affecting drift
Positive frequency-dependent selection
the fitness associated with a trait increases as the frequency of the trait increases in the population Snails must mate with opposite sex having the same shell orientation As right- or left-handed orientation increases, so does its fitness of the same orientation
Negative frequency-dependent selection
the fitness with a trait decreases as the frequency of the trait increases in the population As one mouth morphology (left) becomes dominant, prey become very good at watching the sides attached by that dominant morphology (their right side) This begins to favor mouth morphologies with opposite orientation (right), who have higher fitness feeding on the "less-watched" (left) side
Overdominance (heterozygote advantage)
when a heterozygote (A1,A2) has a higher fitness that either homozygote (A1,A1 or A2,A2) Example: sickle cell trait (autosomal, recessive trait) -A1,A1 no cost, no benefit -A1,A2 no cost, malaria resistant (basically no cost and all benefit) -A2,A2 high cost, malaria resistant Example: Chromosome 6 MLA Cite (preferred mate typically has different MLA) -A1,A1 no cost, reduced immunity -A1,A2 no cost, increased immunity -A2,A2 no cost, reduced immunity
Underdominance (homozygote advantage)
when a heterozygote (A1,A2) has a lower fitness that either homozygote (A1,A1 or A2,A2) Extremely rare Example: New Zealand Lab Mice -A1,A1 (homo white) healthy -A1,A2 (hetero black or white) autoimmune disease -A2,A2 (homo black) severe autoimmune disease When A1 begins above some threshold frequency it goes to fixation When A1 begins below some threshold, it is lost from the population (and A2 goes to fixation)
Direction selection
when one allele is consistently favored over the other, selection drives allele frequencies in a single direction (towards the favor allele) Eventually, the frequency of the allele is "fixed" [1,0] in the population based on the organisms fitnesses and survival in its environment (frequency depends on allele dominance) When A1 dominant
Epistasis
when the alleles at two or more loci interact in non-additive ways
Frequency dependent selection
when the costs and benefits of a trait depend on the frequency of that trait in a population Deals with the effect of phenotype frequencies on other phenotypes, NOT on how fitness is related to allele frequencies
Mendel's Second Law: Law of Independent Assortment
when two or more characteristics are inherited, individual hereditary factors assort independently during gamete production, giving different traits an equal opportunity of occurring together alleles passed to offspring at one locus are independent from alleles passed to offspring at other loci (**only if unlinked**) with Mendelian inheritance, favorable mutations are not lost