Lecture Note
Evolution at Multiple Loci. Linkage, Sex and Quantitative Genetics
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University:
California State University, Northridge -
Course:
BIOL 322 | Evolutionary Biology Academic year:
2006
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Views:
230
Pages:
35
Author:
Enrique Hendrix
Evolution at multiple loci
• Linkage
• Sex
• Quantitative genetics Linkage
• Linkage can be physical or statistical, we
focus on physical - easier to understand
• Because of recombination, Mendel develops
law of independent assortment
• But loci do not always assort independently,
suppose they are close together on the same
chromosome Haplotype - multilocus genotype
• Contraction of ‘haploid-genotype’
– The genotype of a chromosome (gamete)
• E.g. with two genes A and B with alleles A
and a, and B and b
• Possible haplotypes
– AB; Ab; aB, ab
• Will selection at the A locus affect
evolution of the B locus? Chromosome (haplotype)
frequency v. allele frequency
• Example, suppose two populations have:
– A allele frequency = 0.6, a allele frequency 0.4
– B allele frequency = 0.8, b allele frequency 0.2
• Are those populations identical?
• Not always! Linkage (dis)equilibrium
• Loci are in equilibrium if:
– Proportion of B alleles found with A alleles is
the same as b alleles found with A alleles; and
• Loci in linkage disequilibrium if an allele at
one locus is more likely to be found with a
particular allele at another locus
– E.g., B alleles more likely with A alleles than b
alleles are with A alleles Equilibrium - alleles
A locus, A allele p = 15/25 = 0.6 a allele q = 1-p = 0.4
B locus, B allele p = 20/25 = 0.8; b allele q = 1-p = 0.2 Equilibrium - haplotypes
Allele B with allele A = 12; A without B = 3 times; AB 12/15 = 0.8
Allele B with allele a = 8; a without B = 2 times; aB 8/10 = 0.8 Equilibrium graphically Disequilibrium - alleles
A locus, A allele p = 15/25 = 0.6 a allele q = 1-p = 0.4
B locus, B allele p = 20/25 = 0.8; b allele q = 1-p = 0.2 Disequilibrium - haplotypes
Allele B with allele A = 11; A without B = 4 times; AB 11/15 = 0.73
Allele B with allele a = 9; a without B = 1 times; aB 9/10 = 0.9 Disequilibrium graphically Example recap:
• In both populations
– A frequency = 0.6; a frequency = 0.4
– B frequency = 0.8; b frequency = 0.2
• In the disequilibrium population
– Allele B more likely to be found with allele a
than allele A Defining equilibrium
• Intuitive: if knowing whether or not locus 1
genotype is A or a gives you a hint as to if
locus 2 genotype is B or b, then not in
equilibrium
• If knowing genotype of locus 1 tells you
nothing about genotype of locus 2, then loci
are in equilibrium Quick calculation
• In equilibrium if: Haplotype frequency is
product of allele frequencies
• From the equilibrium example:
– AB haplotype was 12 of 25 = 0.48
– A frequency was 0.6; B frequency was 0.8
• 0.6*0.8 = 0.48
– ab haplotype was 2 of 25 = 0.08
– a frequency was 0.4; b frequency was 0.2
• 0.4*0.2 = 0.08 Quantifying disequilibrium
• D coefficient of linkage disequilibrium
= gABgab - gAbgaB
• Ranges from -0.25 to 0.25 Sex, recombination, and
disequilibrium
• Meiosis
mixes up
which alleles
are with
which other
alleles Experimental data,
Clegg et al. 1980 Causes of linkage disequilibrium
•
•
•
•
•
Non-random mating
Selection
Mutations in small populations
Inversions preventing recombination
Immigration/emigration; population
admixture Multilocus selection
• Does
selection at
locus A affect
evolution at
locus B?
• It can, if
alleles at A
and B are
linked Multilocus evolution
• Selective sweep
• Hitch-hiking allele Can selection produce a small
dog with big ears?
• If body size alleles and ear size alleles are
unlinked
• But less effectively if body size alleles and
ear size alleles are linked, or if the same
genes affect both traits (pleiotropy) Humans and linkage
• Huttley et al surveyed over 5000 loci across
22 autosomes
• Most loci unlinked, unless under strong
selection or physically linked
• Selected linked loci within immune system
– Chromosome 6 HLA (MHC in non-humans)
• Physically linked closely paired loci
– Probability of recombination depends on distance Linkage and allele history
• Recall the CCR5 delta 32 mutation?
– In homozygotes prevents entry of HIV into cells
• Frequency around 20% in Europe, 0%
elsewhere
• Delta 32 allele in linkage disequilibrium with
nearby loci GAAT and AFMB
• GAAT alleles and AFMB alleles non-coding
and in equilibrium with each other History of CCR5 delta 32 allele
• Probably arose by mutation in an individual
that just happened to have allele 197 at
GAAT locus and allele 215 at AFMB locus
• New delta 32 favored by selection, and
brought AFMB 215 and GAAT 197 along
for the ride Linkage breakdown
• Delta 32 still non-randomly associated with
GAAT 197 and AFMB 215, but not perfect
– Some recombination has occurred
• Back calculating based on recombination
rate give estimate of delta 32 mutation
appearing ca. 700 years ago (possibly 275 to
1875 years)
• Selective agent may have been bubonic
plague or smallpox What good is sex anyway? Asexuals will win if
• Same number of offspring produced by sex
and asex
• And/or
• Offspring survival not different for sex and
asex
• The fact that most species are sexual suggests
that one or both of these must be wrong Sex and genetic variation
• Asexuals are clones produced by
parthenogenesis; genetically identical to mom
• Sexuals have recombination; genetically
variable offspring different from parents
• Linkage disequilibrium
– If pop in equilibrium, sex has no genetic effect on
its own
– Either drift or multilocus selection Sex and drift
• Sex gets rid of bad mutations
• Asexual females always pass on new bad
mutations
• Muller’s ratchet - mutation accumulation
• In small pops, drift can knock out the
individuals with the fewest mutations
(selection may knock out individuals with
most mutations) Muller’s ratchet
As highest fitness groups lost
by drift, average fitness
declines.
Loss of highest fitness group
by drift exceeds recreation by
back-mutation.
Burden called genetic load. Sex and Muller’s ratchet
• Sex allows recreation of zero deleterious
mutation subpopulation each generation by
recombination
• With asexual reproduction, the zero
deleterious mutation genotypes are missing
(i.e. there is linkage disequilibrium) Muller’s ratchet outcomes
• Very dependent on population size
– Small pop’ affected
• Mildly deleterious mutations more likely to accrue
– Strongly deleterious selected out
• Studies with endosymbiotic bacteria demonstrate
mutation accumulation
– But over long term
– Short term asex strongly favored Sex and selection
• Changing environment favors sex
• ‘best’ genotype today not ‘best’ genotype
tomorrow
• Sex genes favored over asexual genes
because of high fitness of some of the
sexual genotypes in changed environment Sex and co-evolution
• Abiotic environments (water, temperature,
etc) don’t usually change fast enough for
sexuals to win over asexuals
• Biotic environments do: co-evolutionary
arms races
– Evolve resistance to disease, bad for disease,
disease evolves back at you
– Red Queen Hypothesis Do parasites favor sex?
• Lively studied snails and parasitic
trematode worms
• Worms castrate snails (by eating their
gonads!)
• Across 66 New Zealand lakes, the more
parasites the higher proportion of males
– Produced by sexual females
Evolution at Multiple Loci. Linkage, Sex and Quantitative Genetics
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