One way to test these theories is to look at th number of silent vs.

One way to test these theories is to look at th number of silent vs. non-synonymous substitutions over a given region of DNA

are silent point mutations in DNA (no effect on phenotype) more common or less common than non-synonymous changes?

Negative selection: amino acid substitutions are less common than silent DNA substitutions (change is bad) Positive selection: non-synonymous amino acid substitutions

are more common than silent substitutions

Neutral or Selectionist?

Polymorphic sites 1: DNA changes

Some positions are polymorphic (different nucleotides are found) between some of the species

- a single nucleotide is fixed within each species

Other positions are polymorphic within one species, but are otherwise fixed among species

E. papillosa a GGTGCAGTAAACTTTATTACTACTATTTTTAATATACGGTCACCTGGTATAAGAATGGAACGTTTAAGATTATTTGTTTGATCAGTTTTA E. papillosa b .....G.................................................................................... E. patina 06Jam11 .....G..........................C..G.....T.....G..G.C...............T...........G......C.C E. patina 07Dom05 .....G..........................C..G.....T.....G..G.C.........C.....T...........G......C.C E. zuleicae 04Ber03 .....G...........C..A...........C..G..C..T.....A..G.C...............T..................C.. E. zuleicae 04SSal11 .....G..............A.G.........C..G..C..T.....A..G.C...............T........C.........C..

Polymorphic sites 2: amino acid changes

E. papillosa a VYPPLSGPIGHGGASVDLAIFSLHLAGMSSILGAVNFITTIFNMRSPGMSMERLSLFVWSVLVTAVLLLLSLPVLAGAITMLLTDRNFNTSF E. papillosa b .................................................S...............V.......................... E. patina 06Jam11 .................................................T...............F.......................... E. patina 07Dom05 .................................................T...............F.......................... E. zuleicae 04Ber04 .................................................T...............F.......................... E. zuleicae 04Ber06 .................................................T...............F.......................... E. zuleicae 04Boc102 .................................................T...............F.......................... E. zuleicae 06Jam07 .................................................T...............F...................G...... E. zuleicae 07LSS02 .................................................T...............F.......................... E. zuleicae 04SSal03 .................................................T...............F.......................... E. zuleicae 04Boc101 .................................................T...............F.......................... E. zuleicae 07SSal01 .................................................T...............F.......................... E. zuleicae 06Jam03 .................................................T...............F.......................... E. zuleicae 04SSal11 .......................................S.........T...............F.......................... E. zuleicae 04Bocas103 .................................................T...............F.......................... E. zuleicae 04SSal06 .................................................T...............F.......................... E. zuleicae 09Cur105 .................................................T...............F.......................... E. zuleicae 09Cur09 .......S.........................................T...............F.......................... E. zuleicae 07Cur12 .................................................T...............F.......................... E. zuleicae 09Cur13 .................................................T...............F.......................... E. zuleicae 09Cur14 .................................................T...............F..........................

S or T V or F

different amino acids can be fixed between species

different amino acids can occur at a site within one species

Normally, most substitutions that survive to be detected are silent

When non-synonymous changes pile up faster than silent changes (given that codons differ in whether one mutation can change the amino acid), it indicates positive selection is acting to quickly fix mutations before they get lost to drift

E. papillosa a GGTGCAGTAAACTTTATTACTACTATTTTTAATATACGGTCACCTGGTATAAGAATGGAACGTTTAAGATTATTTGTTTGATCAGTTTTA E. papillosa b .....G.................................................................................... E. patina 06Jam11 .....G..........................C..G.....T.....G..G.C...............T...........G......C.C E. patina 07Dom05 .....G..........................C..G.....T.....G..G.C.........C.....T...........G......C.C E. zuleicae 04Ber03 .....G...........C..A...........C..G..C..T.....A..G.C...............T..................C.. E. zuleicae 04SSal11 .....G..............A.G.........C..G..C..T.....A..G.C...............T........C.........C..

1. DNA – 17 polymorphic sites

2. amino acid – 4 polymorphic sites (= non-synonymous changes)E. papillosa a VYPPLSGPIGHGGASVDLAIFSLHLAGMSSILGAVNFITTIFNMRSPGMSMERLSLFVWSVLVTAVLLLLSLPVLAGAITMLLTDRNFNTSF E. papillosa b .................................................S...............V.......................... E. patina 06Jam11 .................................................T...............F.......................... E. patina 07Dom05 .................................................T...............F.......................... E. zuleicae 06Jam07 .................................................T...............F...................G...... E. zuleicae 04SSal11 .......................................S.........T...............F..........................

Evidence for positive selection suggests selection is driving the rate at which mutations are fixed as proteins evolve

Smith & Ayre-Walker (2002) compared ratio of non-synonymous (dN) to synonymous (dS) substitutions within 2 Drosophila species, and between the two species, over the whole genome

- found many sites where there were more non-synonymous changes between the species than within either species

- indicates that selection favored differences between species

- they estimated 45% of amino acid differences between the 2 species had been fixed by positive selection


Begun et al. (2007) found amount of polymorphism was correlated with recombination rate across Drosophila simulans genome

Different regions of the genome can differ in how often crossing over occurs – some places have more, others less

Some genes are more polymorphic than others (have more alleles)

Neutral theory predicts no relationship between amount of genetic polymorphism (# of alleles) and how often crossing over happens

Why does selectionist theory predict a correlation?...


Selection favoring one allele will also tend to drag alleles at nearby or linked loci to high frequency

A B C D E F

a b c d e f

...it will also tend to favor “B” and “D” alleles, if they happen to be linked to “C” on a chromosome


if selection strongly favors “big C” allele of the C gene...

Selection favoring one allele will also tend to drag alleles at nearby or linked loci to high frequency

A B C D E F

a b c d e f



...all these alleles will be lost, unless they can get onto the “winning team” i.e., any chromosome with a C allele

in regions of high recombination, linked loci can escape the effects of selection on nearby genes

crossing over “breaks up the team”

A B C D E F

a b c d e f

Even if selection strongly favors C allele... alleles of other genes can cross over onto C chromosomes

In regions of high recombination, many alleles at linked loci can “hitchhike” onto chromosomes with favorable alleles, and thus survive selection greater overall polymorphism

a b C d e f


Begun et al. (2007) found amount of polymorphism was correlated with recombination rate across Drosophila simulans genome

in regions of low recombination, linked loci can’t escape the effects of selection on nearby genes

A B C D E F

a b c d e f


...all these alleles get lost


The correlation is strong evidence that selection acts on alleles all the time, across the whole genome

Supports selectionist theory, not neutral theory

Non-random mating: Inbreeding

Violates one of the assumptions of Hardy-Weinberg

Can affect genotype frequencies without affecting allele frequencies

Selfing (not the same as cloning)

- many plants and some animals can self-fertilize

- homozygotes always give rise to homozygotes

- heterozygotes produce 1/2 homozygotes and 1/2 heterozygotes

Aa

AA Aa aa

1 : 2 : 1

Non-random mating: Inbreeding

Result:

in every generation of selfing, the # of heterozygotes is halved

- however, the allele frequencies are unchanged thus, inbreeding also causes loss of heterozygosity,

and has a strong evolutionary impact

-

Inbreeding and loss of heterozygosity

Case study: malaria parasite

- most people in New Guinea are infected by only one mosquito

- most reproduction occurs between brother and sister offspring when another mosquito bites an infected person (inbreeding)

prediction: there should be an excess of homozygotes at loci that are polymorphic

- in other words, even when there are a lot of alleles out there, selfing should result in few heterozygotes

Inbreeding and loss of heterozygosity

very polymorphic loci

Coefficient of inbreeding

Inbreeding among more distant relatives has the same effect, but less drastic

Degree of relatedness is reflected in a measure called the coefficient of inbreeding, F

F is the probability that the two alleles in an individual are related by descent from a common ancestor

F = 0.5 for selfing: there’s a 50/50 chance selfing will produce an offspring with both alleles derived from the same parental allele


F is the probability that the two alleles in an individual are related by decent from a common ancestor


Ordinary genotype frequencies predicted by Hardy-Weinberg:

AA Aa aa

p2 2pq q2

In an inbred population, genotype frequencies are given by:

AA Aa aa

p2(1-F) + pF 2pq(1-F) q2(1-F) + qF

-- why? odds of getting a homozygote = sum of 2 possible ways

way #1 - p x (odds of an unrelated p), which is p x p(1-F)

way #2 - p x (odds of a related p), which is pF


In an inbred population, genotype frequencies are given by:

AA Aa aa

p2(1-F) + pF 2pq(1-F) q2(1-F) + qF

test: insert the value F = 0

- this is true for unrelated gametes

- gives you the Hardy-Weinberg genotype odds

Inbreeding depressionAlthough inbreeding doesn’t change allele frequencies, it creates an excess of homozygotes

This exposes loss-of-function alleles, which are normally masked in heterozygotes

- creates lower fitness among offspring of relatives

Inbreeding depression

Two population crashes, in 1980 (27 survivors) and 1989 (11 survivors)

Inbreeding coefficient of survivors (those still alive in the crash year) was much lower than the average value in the year before the crash

ones who survived the terrible winters were the least inbred; inbreeding lowers survival chances when environment goes bad

Keller et al. (1994) followed a population of sparrows (small birds) on a Canadian island for 15 years

inbr

eedi

ng c

oeff

icie

nt

popu

latio

n si

ze

One way to test these theories is to look at th number of silent vs.

Documents

Transcript of One way to test these theories is to look at th number of silent vs.