Evolution at Multiple Loci: Linkage and Sex

EVOLUTION AT MULTIPLE LOCI:
LINKAGE and SEX

Chapter 8 in the 4th edition, Chapter 7 in the 3rd.

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linkage can involve any pair of loci in an organism’s genome
physical linkage of two loci on the same chromosome [Fig. 7.1]
two locus version of Hardy-Weinberg tracks both allele and chromosome frequencies
Haplotype: multilocus genotype of a chromosome or a gamete (haploid genotype)
Linkage disequilibrium determines whether selection at one locus affects allele and genotype frequencies at another locus

Two populations, both with the same allele frequencies:
- Fr(A)=0.6, Fr(a)=0.4,
- Fr(B)=0.8, Fr(b)=0.2
One Population is in Linkage Equilibrium; the other, in Linkage Disequilibrium
A population is in linkage equilibrium (with respect to loci A and B) if an individual's genotype at locus A is independent of the individual's genotype at B [Fig. 7.2a]
- in linkage equilibrium
  - frequency of allele B on allele A chromosomes = Fr(B) on allele a chromosome
    - Fr(B) = 0.8 on both
  - Fr (AB haplotype) = Fr(A)*Fr(B), etc.; e.g. Fr(AB chromosomes) = 0.6*0.8
  - knowing the genotype at one locus is of no use in predicting the genotype at another locus
    - Independent Assortment and Crossing Over

linkage disequilibrium
- There is a nonrandom association between a chromosome’s genotype at one locus and its genotype at another locus (e.g., A and B)
- Frequency of allele B on A chromosomes is not equal to Fr (B on a) [Fig. 7.2b]
- Knowing the genotype at one locus makes it possible to predict the genotype at another locus

in linkage equilibrium, under H-W assumptions, chromosome frequencies remain unchanged from generation to generation.
in linkage disequilibrium, chromosomes frequencies change (they will move closer to equilibrium each generation)

Figure 7.3a: linkage equilibrium.
- Fr(AABB) = Fr(AB)*Fr(AB) = 0.48*0.48 = 0.2304, etc.
Figure 7.3b: linkage disequilibrium
- individuals with fewer than 3 dominant alleles are removed
- survivors are in linkage disequilibrium

The effect of sexual reproduction with random mating is to reduce the level of linkage disequilibrium in populations (Figs. 7.6, 7.7).
Linkage equilibrium or disequilibrium affects the evolution of the population.

If the population is in linkage equilibrium, selection at one locus is independent of selection at other loci.
If a population is in linkage disequilibrium, selection at one locus also changes the allele or genotype frequencies at one or more other loci.’ [Fig. 7.8]

Where did the CCR5-Δ32 allele come from? [Fig. 7.9]
- two neutral loci near the CCR5 locus are close to linkage equilibrium [Fig 7.9]
- linkage disequilibrium between CCR5 and its adjacent neutral loci originated from genetic drift
- a mutation forming the CCR5-Δ32 allele occurred on a chromosome with a Δ32-197-215 haplotype and was strongly selected for
Estimating the age of the CCR5-Δ32 mutation [Box 7.4, Fig. 7.9]
- decrease of linkage disequilibrium to its present rate would have taken 275 to 1875 years, best estimate 700 years ago.
- Genetic bottleneck from smallpox or bubonic plague favored the Δ32 mutation

Linkage disequilibrium is reduced by sexual reproduction with random mating
Many species are capable of both sexual and asexual reproduction (aphids, Volvox, hydra [Figs. 7.11, 7.12]).
parthenogenesis: reproduction from unfertilized eggs

null model (Maynard Smith, 1978) has two assumptions
1. number of offspring a female can produce depends only on the amount of food she can gather, not her mode of reproduction
2. The probability that an offspring will survive to reproduce does not depend on whether that offspring was produced sexually or asexually
Difficulties and Costs Associated with Sexual Reproduction
1. costs in time, energy, increased predation risk
2. sexual reproduction is slower than asexual. The fraction of the population that are asexual females increases every generation. [Fig. 7.13]
3. costs of meiosis: offspring only share half of each parent's genes. if the environment is stable the recombinant offspring may not be well adapted.
Maynard Smith's first assumption is violated by species in which males contribute to raising offspring. However, in most species, including mammals, males only contribute genes. Maynard Smith's first assumption is correct.
Maynard Smith's second assumption is not correct. Under some conditions, descendants produced by sexual reproduction have a higher fitness than descendants produced by asexual reproduction. Experiment with flour beetles shows this [Fig. 7.14].
sex reduces linkage disequilibrium.

asexual reproduction leads to accumulation of deleterious alleles (genetic load), which can cause extinction.
Mueller's ratchet (Fig. 7.15).
1. Experimental demonstration (Fig. 7.16): bacterial populations subjected to periodic bottlenecks over 1700 generations.
2. Muller's ratchet is long-term, requires many generations to accomplish

RED QUEEN HYPOTHESIS (Van Valen)

To avoid extinction, a population must constantly evolve in response to the changing environment: physical and biotic pressures (predation, parasites, competition, availability of prey or food plants, etc.).
Sex is a short-term adaptation to rapid environmental change.
Sex recreates now-favorable multilocus genotypes that were recently eliminated by selection and sexual reproduction is therefore strongly selected for.
Evolutionary Arms race
- Parasites and their hosts are engaged in a constant struggle, with the host evolving defenses and the parasite evolving mechanisms to counter the host's defenses. A parasite might select in favor of a certain multilocus genotype in one generation, and in favor of a different multilocus genotype in another generation. [Fig. 7.17]
Parasites have been suggested as selective agents for sex. A higher proportion of female snails (Potamopyrgus antipodarum, in New Zealand) are of the sexual type in populations with a high incidence of parasitism from trematodes. [Fig. 7.18]