18feblecture upload

announcements / reminders

• an easy 5 points is available by Sunday 23 Feb, midnight The mid-term assessment survey (a quiz on Beachboard)! Results from this help me to know how to adjust the class for the rest of the semester, if needed. Please take the survey!

• there are still spots available in one of the SI sections! M/W/F 10-1050 am; contact Lena Vincent ([email protected])

• second exam is in three weeks – Tuesday 11 March!

so far...

• you know where information is held in cells (DNA!), and how that information is used to make or modify other key molecules of living cells (proteins! carbohydrates! lipids!). You understand the importance of genetic information in determining an organism's structure and function.

• you know how organisms replicate their genetic information and distribute it to daughter cells. In addition, you know how those cell division events (binary fission, mitosis, meiosis) fit into the processes of asexual and sexual reproduction.

• you understand the basics of how traits are inherited in sexual reproduction, and how those inheritance patterns are related to processes that happen in meiosis (e.g., segregation of alleles, and independent assortment of chromosomes/traits)

remember the overall goals of the course?

I want you to leave this course with:• a basic understanding of the scientific method

• a broad overview of the history and diversity of life on earth, from ~4 billion years ago to now

• an understanding of the evolutionary mechanisms by which that diversity arose

✓

At this point we have enough background knowledge to address this issue! That's what we'll do for the next ~3 weeks.

1) a bit more about how how genotype affects phenotype...

2) what is evolution?

3) where does genetic variation in populations come from?

4) describing the genetic makeup of populations allele frequencies genotype frequencies

5) a "null model" for evolution: Hardy-Weinberg equilibrium

6) mechanisms of evolution: mutation gene flow genetic drift natural selection nonrandom mating

today's goals

how does genotype affect phenotype?

• so far we've seen mostly Mendel's examples, where there are two clearly distinct alternative traits for each character, e.g.:

• the phenotypic variation in these cases can be described as "either-or" of the distinct alternatives, or... "____________ variation" (slightly different definition than in second lecture)

• qualitative variation is usually caused by allelic variation at a single locus, like we've already talked about.

• at the population level, such traits have a bimodal* distribution

(*if there are only two alleles in the population)


• example: purple vs. white flower color is caused by the two alleles a pea plant has at the flower color locus)


• another example: wet earwax vs. dry earwax in humanswet, sticky, and yellow or brown

(~50% lipid)

dry, crumbly, and grayish (~30% lipid)


• another example: wet earwax vs. dry earwaxwet, sticky, and yellow or brown

(~50% lipid)

dry, crumbly, and grayish (~30% lipid)

• this is a simple either-or trait, with wet (W) dominant over dry (w)

• we even know what locus is involved – it's the gene for a protein called ABCC11. ABCC11 protein is embedded in the plasma membrane, where it transports molecules across the membrane.

W allele: ...ATT GCC AGT GTA CTC GGG CCA ATA TTG ATT ATA CCA...

... Ile Ala Ser Val Leu Gly Pro Ile Leu Ile Ile Pro ...

w allele: ...ATT GCC AGT GTA CTC AGG CCA ATA TTG ATT ATA CCA...

... Ile Ala Ser Val Leu Arg Pro Ile Leu Ile Ile Pro ...


• many traits aren't "either-or", but instead vary along a continuum

• the phenotypic variation in these cases can be described as "______________ variation"

• quantitative variation in a trait is usually caused when that trait is affected by allelic variation at many loci

• example: human bodyheight is affected byalleles at ~180 loci!

• at the population level, such "polygenic" traitsoften have a normal (bell-shaped) distribution







today's goals

what is evolution?

• the term simply means "change"

• but biologists use it most specifically as meaning:

changes in allele frequencies in populations over time

(population = a group of organisms of the same species living in the same area at the same time, and interbreeding with each other)

what is evolution?

• the term simply means "change"

• but biologists use it most specifically as meaning:


(population = a group of organisms of the same species living in the same area at the same time, and interbreeding with each other)

if allele frequencies are to change over time in populations, there needs to be some genetic variation. What is the source of genetic variation in populations?







today's goals

where does genetic variation come from?

new alleles are formed by mutation: change in an organism's nucleotide sequence

• mutations are often (but not always) associated with DNA replication events; in that case, mutations are basically copying errors

• there are many kinds of copying errors! substitution of a single base in a gene (a "point mutation"). For protein-coding genes, this may or may not have any effect on the amino acids the gene codes for

AUC UCU GCU CCGIso Ser Ala Pro

AUC UCA GCU CCGIso Ser Ala Pro

AUC UAU GCU CCGIso Tyr Ala Pro

no change inprotein

change inprotein


• there are many kinds of copying errors! insertions or deletions: addition/loss of one or more bases in a gene. If the gene codes for a protein, a number of bases that is not a multiple of 3 is gained or lost, this results in a "frame-shift mutation", changing all the amino acids in the protein!

AGC ACU GCU CCGSer Thr Ala Pro

multiple of 3; in this,loss of an a.a.

not multiple of 3;all a.a. change!

AGC ACU GCU CCGSer Thr Ala Pro

AGC ACU GCU CCG Ala Leu Leu


some mutations don't actually affect the nucleotide sequence of individual genes, but instead add or remove entire genes!

gene _______________ – mistakes in meiosis sometimes lead to duplication of entire genes (or groups of genes), so that a chromosome that previously had one copy of some gene (e.g., actin)now ends up with two or three or more copies!


most mutations are copying errors... so it makes sense that organisms that do more copying generate mutations more frequently!

-- organisms that have very rapid generation times – e.g., viruses, bacteria – copy DNA for reproduction very frequently. Thus in a given time period – say, a year – a population of bacteria will have generated and passed on many mutations to their offspring.

-- in contrast, organisms with long generation times (e.g., people) don't copy DNA for reproduction very often, so the total number of mutations we generate and pass on per unit time is relatively low.


are mutations good, or bad?

-- mutations sometimes have no effect on phenotype at all (e.g., if they don't cause an a.a. change in a protein, or they cause a change that doesn't affect tertiary or quaternary structure) (these are called ___________ mutations)

-- mutations often have negative effects on phenotype (e.g., frameshift mutations are cause a protein to be nonfunctional, and that is usually a problem)

-- mutations rarely have positive effects on phenotype


do mutations happen because an organism/population/species "needs" them to deal with some specific problem?

-- NO! Mutations arise randomly with respect to the "needs" of the organism

E.g., if a population of fish is living in a pond that is warming from year to year, any mutations that occur will be random with respect to location in the genome. So the fishes will not have more mutations in genes associated with thermotolerance (even though those beneficial mutations – which remember, are rare! – in those genes might be especially useful at the time!)


one other key source of variation: sexual reproduction

-- crossing over, independent assortment, and random fertilization don't generate new alleles – but they generate new combinations of alleles, both within loci and among loci

-- the book uses a nice analogy here – the proceses of sexual fertilization don't make new alleles, but they "shuffle existing alleles and deal them at random to provide [new] individual genotypes"







today's goals

• evolution is:


if evolution is defined as change in allele frequencies, we need to know how to describe allele frequencies (and, it turns out, genotype frequencies) so that we can observe it...

describing the genetic makeup of populations


• review: different forms of a gene are called alleles. A diploid organism can have at most how many different alleles at a particular locus?


• review: different forms of a gene are called alleles. A diploid organism can have at most how many different alleles at a particular locus? TWO

• but the population may contain many more than two alleles! The gene pool is the sum of all copies of all alleles at all loci in a population.

• what we need are some simple metrics by which to describe gene pools, to see if they change from generation to generation...


how can we describe genetic variation in a population?

You could get an exactcount of allele freqs ina popn... but to do that you'd have to examine every individual!

Normally we estimate popnfrequencies by taking a random sample of individuals from the popn

1) allele frequencies – what is the proportion of a given allele in a population?


how to calculate allele frequencies(for the simplest case: only one allele at that locus in the popn)(this population is monomorphic at this locus; that allele is said to be fixed in the population)

• say the allele present in the popn is

A (let's call its frequency p)

• since there is only one allele, p must be equivalent to 1 (all alleles in the popn are A)

€

p =number of copies of A in the population

total number of alleles at that locus in the population


how to calculate allele frequencies(for a simple case: only two alleles at that locus in the popn)(this popn is ________________ at this locus)

• say the two alleles present in the popn are:A (let's call its allele frequency p)a (let's call its allele frequency q)

note: p + q = 1!

€

p =number of copies of A in the population


€

q =number of copies of a in the population



how to calculate allele frequencies(for a simple case: only two alleles at that locus in the popn)

The possible genotypes are AA, Aa, aa

NAA = number of individuals of genotype AA

NAa = number of individuals of genotype Aa

Naa = number of individuals of genotype aa

The total number of individuals in the population is N = NAA + NAa + Naa

The total number of alleles at this locus in the population is...?



Let p = frequency of allele A in the population.

Let q = frequency of allele a in the population.

p = 2NAA + NAa

2N

q = 2Naa + NAa

2N

note: p + q = 1!



• since p + q = 1...

if you know p, you can figure out q!

q = 1 – p

if you know q, you can figure out p!

p = 1 - q


two examples...

clicker question 3

You have 100 snapdragon plants growing in your garden. 68 of them are red (42 homozygous dominant, 26 heterozygous: hey, you must have done a bunch of test crosses to figure that out!), and 32 are white (homozygous recessive). What are the allele frequencies of R (red) and r (white) in the population?

A. R=.90, r=.10

B. R=.33, r=.67

C. R=.55, r=.45

D. R=.75, r=.25

E. R=.67, r=.33


the allele frequencies of these two popns are identical... but how those alleles are distributed among individuals is very different!

so... we need another descriptor of genetic variation in addition to allele frequencies – genotype frequencies!


how to calculate genotype frequencies

€

=

number of individuals with that

particular genotype in the population

total number of individuals in the population

frequency of a particulargenotype

e.g. NAA=90/200 = 0.45

NAa=40/200=0.2

Naa=70/200=0.35

these must add up to 1 too!

clicker question 4

You have 100 snapdragon plants growing in your garden. 84 of them are red (49 homozygous dominant, 35 heterozygous), and 16 are white (homozygous recessive). What is the frequency of the heterozygous genotype in the population?

A. 0.16

B. 0.32

C. 0.35

D. 0.49

E. 0.98


wait a minute... why do we care about this, again? well, evolution is change in allele frequencies of populations over time... so we clearly need to be able to measure allele frequencies if we want to describe evolution happening.

genotype frequencies indicate how allelic variation is distributed among individuals in the population; we'll see why that is important in a second.

To identify when evolution is occurring, we can quantify allele frequency in a population over time! (but that takes time, and doesn't

help us understand what is causing the change)

Alternatively, we can use a mathematical model to predict what a population should look like at one moment in time if NO evolution is occurring. When evolution IS occurring, data from a real population

will not match the model's predictions! "Deviations" from the predictions help us understand what is causing the change.







today's goals

Hardy-Weinberg equilibrium

• in a population of sexually reproducing organisms that is NOT evolving, allele frequencies (by definition) do not change from generation to generation

• if no evolution is occurring, the different genotypes should appear in frequencies that are easily determined from allele frequencies using a simple mathematical model (the Hardy-Weinberg equation); these genotype frequencies also should not change from generation to generation

• for a real population to be "in HW equilibrium" – where predicted genotype frequencies match real genotype frequencies in the population, and we infer that no evolution is occurring – five conditions need to be met:

The HW equation uses a population's allele frequencies to predict "equilibrium" (no evolution

occurring) genotype frequencies in that population


Conditions that must be met for a real population to be in HWE:

1) there is no mutation

2) there is no gene flow (movement of individuals in or out of the popn, or reproductive contact with other popns)

3) population size is extremely large (infinite, actually)

4) there is no natural selection (differential survival or reproduction of individuals with different genotypes)

5) mating is random

(aside: probability in "individual-level" crosses)

-- we've already used probability (and Punnett squares) to estimate the chances of getting particular genotypes in crosses between two individuals, right?

-- in crosses between two individuals,each parent can only produce gametesthat all carry one allele (if the parent ishomozygous at that locus), or gameteswhere half carry one allele, and halfcarry the other (if the parent is heterozygous at that locus)

-- from those probabilities, one can easily calculate the probability of getting offspring with particular genotypes in the offspring generation


-- the HW equation does exactly the same thing, except at the population level!

-- at the population level, the probabilityof getting a gamete with one or the other allele depends on allele frequency in the population

-- if you know allele frequencies in the parental population, you can estimate the frequencies of each kind of gamete they produce... and then you can easily use probability to figure out chances of getting particular genotypes in the next generation... which is genotype frequency!


-- the book illustrates this with what is basically a "population-level" Punnett square

-- but it's easier to figure this out using simple probability

Prob (CrCr) = p2 = 0.8 x 0.8

Prob (CrCw) = p x q = 0.8 x 0.2

Prob (CwCr) = q x p = 0.2 x 0.8

Prob (CwCw) = q2 = 0.2 x 0.2


-- remember that probabilities of all the possible outcomes of an event have to sum to 1!

-- so, the HW equation for predicting equilibrium genotype frequencies is this:

€

p2 + 2pq+q2 =1

frequency of homozygous

dominant

frequency of homozygous recessive

frequency of heterozygotes

you need to know this equation, and you need to be able to work through word problems using it!!!

clicker question 5 (ungraded)

A randomly mating population of 100 dairy cattle contains a recessive allele causing dwarfism. If there are 16 dwarf calves in the population, what is the frequency of heterozygous carriers of the allele in the entire herd? (Assume that the population is in HW equilibrium).

A. 16% (0.16)

B. 32% (0.32)

C. 48% (0.48)

D. 64% (0.64)

E. 96% (0.96)

clicker question 6 (ungraded)

You have 100 snapdragon plants growing in your garden. 20 are homozygous dominant, 20 are heterozygous, and 60 are homozygous recessive for flower color. Is this population in Hardy-Weinberg equilibrium?

A. Yes

B. No

C. Not enough information given


wait – why do we care about HW equilibrium, again? -- HW equilibrium is where a non-evolving population should be! It can only be there if the following conditions are met:

conditions for HW equilibrium 1) no mutation 2) no gene flow 3) infinite population size 4) no natural selection 5) random mating


wait – why do we care about HW equilibrium, again? -- HW equilibrium is where a non-evolving population should be! It can only be there if the following conditions are met:

conditions for HW equilibrium 1) no mutation 2) no gene flow 3) infinite population size 4) no natural selection 5) random mating

known evolutionary mechanisms 1) mutation 2) gene flow 3) genetic drift 4) natural selection 5) nonrandom mating

so if a real population is not at HW equilibrium for a locus, we know that one or more of those evolutionary mechanisms is acting at that locus!

how the real population deviates from HW equilibrium also gives us some insight into which mechanism is acting







today's goals

mechanisms of evolution: mutation

1) mutation – any change in the nucleotide sequence of DNA -- this is the ultimate origin of genetic variation!

-- mutation rates are usually low~1 mutation per 109 base pairs per generation

Since human gametes contain ~3x109 base pairs, each human gamete has ~3 new mutations; each zygote carries ~6 mutations. That seems like a lot, but the human genome contains ~20,000 genes... so few new alleles arise per individual per generation.

but... since the human population is ~7 billion, humans as a population accumulate ~42 billion new mutations each generation!

mechanisms of evolution: mutation

1) mutation – any change in the nucleotide sequence of DNA

-- if mutation is occurring in a population, it doesn't actually cause much deviation from HWE, because:

a) it's relatively rare – the rate at which mutations arise is usually pretty low

b) new alleles formed by mutation start out at extremely low frequencies! Thus they have very little effect on e.g. predicted genotype frequencies

mechanisms of evolution: gene flow

2) gene flow – movement of genes among populations

-- caused by migration of adult individuals among populations, or by migration of gametes (that is, reproductive contact!) between two populations

-- movements ofgenes into a population can add new alleles to that population,or influence thefrequencies ofexisting alleles.

-- gene flow between two populations tends to make them more similar to each other; if there is enough gene flow, they become one gene pool!

mechanisms of evolution: genetic drift

3) genetic drift – random changes in allele frequencies from generation to

generation due to "sampling error"-- if only a small subset of individuals from a population reproduce, they are unlikely to contain alleles at the true population frequency, just by chance

-- example: drift inallele frequencies in a small populationof plants


3) genetic drift-- drift has more effect in small populations compared to large; however, in populations of finite size it is always having an effect!

-- drift causes allele frequencies to change at random, often in different directions from generation to generation

-- drift tends to reduce genetic variation: rare alleles tend to get lost!


3) genetic driftan illustration of the effects of popn size on drift... ten simulations of changes in allele frequency due solely to chance in three popns: 20, 200, and 2000 individuals.(Frequency of the allele starts at 0.5 in each case; each line shows results from one simulation)

-- the allele gets fixed (frequency=1) or is lost (frequency=0) only in the smallest population

-- allele frequency is much less variable in the largest population


3) genetic driftWe often observe two special cases of genetic drift...

population bottlenecks – a population that is reduced dramatically in size usually loses genetic variation because of drift


population bottlenecks – a population that is reduced dramatically in size usually loses genetic variation because of drift

example –northern elephant seals

-- before 1800s used to be very abundant on west coast

-- in 1800s hunted for oil until thought to be extinct in 1884

-- ~30 were rediscovered in 1892; since then, the population has recovered to ~200,000 animals

-- at the "bottleneck" of ~30, most of the genetic variation in the population was lost; even now, the original genetic diversity has not been regained.


3) genetic driftWe often observe two special cases of genetic drift...

founder effects – when a new population is started by just a few immigrants, those immigrants usually carry only a random subset of the variation in the original population

Lots of examples in human popns! E.g.:-- in 1814, 15 British colonists founded a settlement on the islands of Tristan da Cunha, in the South Atlantic

-- by chance, one carried a recessive allele for a particular form of blindness (retinitis pigmentosa)

-- the frequency of that allele in the founding popn was MUCH higher than that in the British population at large

mechanisms of evolution

next time: natural and sexual selection!

essential vocabularyqualitative variation

quantitative variation

polygenic traits

normal distribution

evolution!

population

mutation

point mutation

insertion/deletion

frame-shift mutation

gene duplication

gene pool

allele frequency

fixed

monomorphic

polymorphic

genotype frequency

Hardy-Weinberg equation, equilibrium

gene flow

genetic drift

sampling error

population bottleneck

founder effect

study questions

define the word "evolution"

where does genetic variation in populations come from?

are mutations typically beneficial, neutral, or harmful?

do mutations arise in response to the "needs" of an organism, or randomly in a population?

how many alleles can be present at a locus in a diploid individual, vs. in a population of diploid individuals?

be able to calculate actual allele and genotype frequencies when given data about a population!

can two populations have the same allele frequencies, but different genotype frequencies?

study questions

how can we use the Hardy-Weinberg equation to identify cases where evolution is or is not occurring?

what are the conditions that a population must meet to be in HWE?

understand how to use the HW equation to solve word problems!

mutation can change allele frequencies in a population, but not very much – why not?

why does gene flow between two populations tend to make them more similar to each other?

what is genetic drift, and why does it cause allele frequencies to fluctuate randomly? Why does it affect small populations more than large populations? And why does it tend to reduce genetic variation?

18feblecture upload

Documents

genetic variation

wet earwax

allelic variation

phenotypic variation

lecture qualitative

wet w dominant

dry earwaxwet

segregation of alleles