Life without Sex Here’s what it looks like. Bdelloid rotifers gave up sex tens of millions of years ago! Yet somehow, they have survived. There are now more than 450 female only species.

Life without Sex Here’s what it looks like. Bdelloid rotifers gave up sex tens of millions of years ago! Yet somehow, they have survived. There are now more than 450 female only species.

Life without Sex What type of reproduction do bdelloid rotifers exhibit? Parthenogenesis Parthenos (Gk) virgin, genesis (Gk) creation.

Life without Sex What are the benefits of non-sexual reproduction? Males do not produce offspring. Every female does produce offspring. What are the consequences? The population can grow larger without males.

Life without Sex What are the disadvantages of sexual reproduction? Sexual reproduction = Time and energy Need to find a mate Mate may need to provide resources (material and nutritional) to prove worthy. Risk of STDs (humans, other species?)

Life without Sex Bdelloid rotifers are susceptible to a fungal pathogen. If the pathogen can infects one rotifer, what are the implications for the population of rotifers? The pathogen can infect the rotifer’s kin. They are clones, and hence genetically identical. How do rotifers escape this pathogen? They outlast them under desiccating conditions.

Life without Sex Bdelloid rotifers escape their pathogens by going dormant. But this is not possible for all organisms. Asexual reproduction + susceptibility to pathogen/predator = extinction There is a strong connection to sexual reproduction and the evolutionary arms race between predator/prey or pathogen/host.

The Red Queen hypothesis Life with Sex The Red Queen hypothesis As the Red Queen told Alice, “it takes all the running you can do, to keep in the same place.” Similarly, animals and plants must continually adapt and evolve just to avoid going extinct. (Illustration by Sir John Tenniel from Lewis Carroll’s “Through the Looking-Glass,” 1871)

Evolution at Two Loci Evolution at Two Loci Linkage Disequilibrium Mechanism that creates Mechanisms that eliminate Ramifications of Linkage Disequilibrium Does it exist Reasons for measuring Significance of Sex Asexual Reproduction Advantage of Sexual Reproduction

Evolution at Two Loci Expand on Hardy-Weinberg one locus model & consider two loci simultaneously. The multilocus genotype of a chromosome or gamete is referred to as its haplotype. Independent assortment is based on chromosome segregating, not loci segregating. Mendel’s law of independent assortment: This principle states that the alleles for a trait separate when gametes are formed. These allele pairs are then randomly united at fertilization. Some genes on a single chromosome are linked because they are not free to undergo independent sorting. Tend to be passed on as a single unit.

Evolution at Two Loci Population Genetics is based on Hardy-Weinberg equilibrium Simple (Allelic Frequencies) and Accurate (predicts evolution) Problem: Tracks a single gene locus Genomes contain thousands of loci. A trait may be affected by a culmination of many of these loci. Selection pressures on these other loci may alter trait under examination. Question: Do we need to worry about selection at other Loci? Sometimes… Need to know if system is in Linkage Equilibrium or Linkage Disequilibrium.

Evolution at Two Loci Linkage Equilibrium – When the genotype at one locus is randomly distributed with respect to genotype at the other locus. Allele frequencies in both populations are the same.

Evolution at Two Loci Linkage Equilibrium – When the genotype at one locus is randomly distributed with respect to genotype at the other locus. But the populations are not identical. Chromosome frequencies in both populations are not the same. e.g. The frequency of chromosome AB differs.

Evolution at Two Loci Linkage Equilibrium – When the genotype at one locus is randomly distributed with respect to genotype at the other locus. Chromosome frequencies are calculated by multiplying allele frequencies. A = 0.6, B = 0.8 AB = 0.6 x 0.8 = 0.48 Chromosome frequencies cannot be calculated by multiplying allele frequencies. A = 0.6, B = 0.8 AB = 0.44

Evolution at Two Loci First lesson of 2 locus H-W: Populations can have identical allele frequencies, but different chromosome frequencies. But the populations are not identical. Chromosome frequencies in both populations are not the same. e.g. The frequency of chromosome AB differs.

Evolution at Two Loci First lesson of 2 locus H-W: Populations can have identical allele frequencies, but different chromosome frequencies. The frequency of B on A is the same for both chromosomes. The frequency of B on A are not the same.

3 conditions are true for a pair of loci in linkage equilibrium. Evolution at Two Loci Linkgage Disequilibrium defined: when there is a nonrandom association between a chromosome’s genotype at one locus and its genotype at the other locus. Linkage Equilibrium – When the genotype at one locus is randomly distributed with respect to genotype at the other locus. 3 conditions are true for a pair of loci in linkage equilibrium.

Evolution at Two Loci Linkage Equilibrium – When the genotype at one locus is randomly distributed with respect to genotype at the other locus. 1. The frequency of B on chromosomes carrying allele A is equal to the frequency of B on chromosomes carrying allele a.

Evolution at Two Loci Linkage Equilibrium – When the genotype at one locus is randomly distributed with respect to genotype at the other locus. 2. The frequency of any chromosome haplotype can be calculated by multiplying the frequencies of the constituent alleles. A = 0.6, B = 0.8 AB = 0.6 x 0.8 = 0.48

Evolution at Two Loci Linkage Equilibrium – When the genotype at one locus is randomly distributed with respect to genotype at the other locus. 3. The quantity D, known as the coefficient of linkage disequilibrium, is equal to “0” Where: gAB = frequency of AB gab = frequency of ab gAb = frequency of Ab gaB = frequency of aB D= (gAB)(gab)-(gAb)(gaB) = 0 D = ? D = 0.48 x 0.08 – 0.12 x 0.32 D = 0.0384 – 0.0384 = 0

Evolution at Two Loci D= (gAB)(gab)-(gAb)(gaB) = 0 D = ? D = 0.48 x 0.08 – 0.12 x 0.32 D = 0.0384 – 0.0384 = 0 0.48 0.08 0.32 0.12

Evolution at Two Loci Reasons for Linkage Disequilibrium Selection on multilocus genotype Predation of certain individuals Result: Fewer offspring with certain C-some configurations

Evolution at Two Loci Reasons for Linkage Disequilibrium Genetic Drift Mutations spontaneously occur in a population altering allelic frequency. Selection that favors this mutation may increase degree of disequilibrium

Evolution at Two Loci Reasons for Linkage Disequilibrium Population admixture Combining two gene pools with different allelic combinations

Evolution at Two Loci Selection on Multilocus Genotype Predation of selective individuals in a population Survival of phenotypes sized >13 (65.28% population) Elimination of certain genotypes creates disequilibrium

Evolution at Two Loci Selection on Multilocus Genotype D= (gAB)(gab)-(gAb)(gaB) = 0 0.1536 D = ? 0.0576 D = 0.4416 x 0.0 – 0.0576 x 0.1536 D = 0 – 0.0088 = - 0.0088 0.4416 ab = 0.0

Evolution at Two Loci Genetic Drift Change in Frequency of alleles in a population resulting from sampling error. Chance variation in survival and/or reproductive success. Non-adaptive evolution. Though mutation and selection would seem to be the forces at work, - this process could only operate in a finite (small ) population. In a large population, A -> a would occur many times on both chromosomes. Selection would favor ab and aB chromosomes.

Evolution at Two Loci Population Admixture Populations are in Linkage Equilibrium Upon mixing, Locus A and B are no longer in equilibrium AB and ab combinations are in excess

Evolution at Two Loci What eliminates linkage disequilibrium? Sex!

Evolution at Two Loci What eliminates linkage disequilibrium? Genetic recombination Crossing over and outbreeding brings together chromosomes with different haplotypes. Crossing over breaks up old combinations of alleles and creates new ones. Genetic recombination – the creation of new combinations of alleles during sexual reproduction. Genetic recombination randomizes genotypes at one locus with respect to genotypes at another locus. Reduces the frequency of overrepresented haplotypes.

Evolution at Two Loci Linkage disequilibrium is reduced at a predictable rate. The rate of decline is proportional to the rate of recombination (r) between two loci. Linkage disequilibrium changes by D’ = D(1-r) Closely linked loci. Free recombination

Evolution at Two Loci Genes exist in a linear fashion along the chromosome Variable amount of exchange occurs between any two genes along a chromosome (distance). Linked genes may not always travel as a group, because of crossover. Recombination of alleles between the homologous chromosomes - Randomizes genotypes Reduces over represented combos (e.g. AB) and increases under represented combos (e.g ab)

Most pairs of loci are in linkage equilibrium. Evolution at Two Loci Disequilibrium between loci falls as a function of distance on the chromosome. Most pairs of loci are in linkage equilibrium.

Evolution at Two Loci Ramifications of Disequilibrium If loci are in disequilibrium, then selection on one loci affects other. Single-locus population genetic models will make inaccurate predictions If loci are in equilibrium, then selection on one loci doesn’t affect other. Good news: Sex is really good at reducing Disequilibrium Really good news: Most pairs of loci are in equilibrium most of the time. Single locus models will work well most of the time

Evolution at Two Loci Case study – Clegg et al. (1980) Fly populations set up in disequilibria. But quickly (than expected) go to equilibrium.

Evolution at Two Loci The downside of linkage equilibrium? Linkage disequilibrium Selection at locus A changes frequency at locus B too. Population genetic studies examining locus B alone will make incorrect predictions about its evolution. Genetic hitchhiking. – change in the frequency of an allele due to selection on a neighboring allele. Makes it difficult to associate a particular allele with a disease.

Evolution at Two Loci The downside of linkage equilibrium? Mutation of the L503F allele (C -> T) strongly associated with Crohn’s disease. L503F mutation is adaptive. It increases the transport of an antioxidant – ergothioneine. Does L503F contribute to Crohn’s disease? Probably not. L503F probably in linkage disequilibrium with nearby genes that do play a role in Crohn’s disease. Better candidates for Crohn’s disease. Significant link between L503 F and Crohn’s No link between L503 F and Crohn’s

Evolution at Two Loci Calculation of linkage disequilibrium permits estimation of when a mutation appeared. L503F appeared as a unique mutation. Rose to high frequency due to selection. Frequency of L503F high in old world. Linkage disequilibrium decaying under the influence of recombination. Knowing the rate of recombination, age of the L503F allele can be calculated. Estimated to be 12,000 years old.

The Adaptive Significance of Sex Squeezing offspring out like this Should lead to Lots of organisms do it. But they also do this. Why? 2X as many offspring in 3 generations

The Adaptive Significance of Sex John Maynard Smith (1978) – developed the null model of reproductive mode. Considers the fate (which outcome is more likely) of two populations that differ in reproductive mode: 1: Females reproduce asexually. 2. Females reproduce sexually. An Evolutionary Paradox! Smith made 2 assumptions: A female’s reproductive mode does not affect how many offspring she makes. A female’s reproductive mode does not affect the probability that her offspring will survive. But it doesn’t! Even asexual organisms reproduce sexually at some time. This model should result in this – the asexual mode should dominate Jaquiery et al. 2013 PLOS

The Adaptive Significance of Sex A thought experiment regarding the two assumptions. Which is likely to be violated? A female’s reproductive mode does not affect how many offspring she makes. This is violated for any species in which the male provides some form of parental care. This would seem to enhance the reproductive output compared to asexual species. But – for most species, parental care by the male is usually lacking. So reproductive output of a female should not differ between sexual and asexual. 2. A female’s reproductive mode does not affect the probability that her offspring will survive. This would appear to be the assumption that is most likely violated

The Adaptive Significance of Sex Populations used environment to select against deleterious mutants. The evidence. Caenorhabditis elegans. Obligately outcrossing males and females Hermaphrodites and males Obligate selfing hermaphrodite Reduced fitness likely due to mutations passed on to offspring. Which offspring? All of them.

The Adaptive Significance of Sex The evidence. Caenorhabditis elegans. Obligately outcrossing males and females Hermaphrodites and males Obligate selfing hermaphrodite Reduced fitness likley due to mutations passed on to offspring. Increase the mutation rate

The Adaptive Significance of Sex The evidence. Caenorhabditis elegans. Obligately outcrossing males and females Hermaphrodites and males Obligate selfing hermaphrodite Reduced fitness likley due to mutations passed on to offspring. Fraction of offspring fathered by males evolves. Increase the mutation rate

The Adaptive Significance of Sex The evidence. Caenorhabditis elegans. Greater mutation rate selects for greater outcrossing. Take Home Message: Sexual reproducing individuals produce offspring with a higher degree of Fitness.

Population Genetics and Sex Sex results in Crossing over and Random matings in a population Main consequence of sex is to Reduce Linkage Disequilibrium. If a population is in Linkage Equilibrium, then sex has no effect or benefit. 2 main events make Sex a Benefit by driving populations toward Equilibrium. Genetic Drift and Mutation - Sex restores lost genotypes Changing Environments - Sex recreates favorable combinations for new environments

Population Genetics and Sex Muller’s Ratchet (1964) Argues that asexual populations are doomed to accumulate deleterious mutations. Each mutation group (e.g. 0 mutations, 1 mutations) is a subpopulation. If they are small, they may “drift” to extinction. (zero mutation in this example) This leaves small populations with greater number of mutations. “click” – the ratchet Loss of a group due to drift more likely than re-creation of a group (e.g. 0 mutations) via a back mutation. Genetic load – burden imposed by the accumulation of mutations. Load becomes so great that population goes extinct via selection against multiple deleterious alleles.

Population Geneticists and Sex Muller’s ratchet (1964) Sex breaks the ratchet by recreating favorable multilocus genotypes If a no-mutation group is lost, it can be reconstituted by outcrossing and recombination. The crux of Muller’s ratchet is that linkage disequilibrium is created by genetic drift. Sex reduces linkage disequilibrium by re-creating missing genotypes.

Selection, Parasites, Environmental Change and Sex In a Constant Environment: Asexual offspring have the same fitness as mother (proven design works again, and again, and again, and again……) Sexual offspring may not survive well (they are new combinations – unproven designs) In a Changing Environment: Asexual offspring are the same design in a changing world. If the single combination of alleles is not successful, then extinction. Sexual offspring are new combinations. At least one combination may work in a new environment. Persistence.

Selection, Parasites, Environmental Change and Sex C. elegans experiment. 3 Treatments 1) Control – challenged with heat killed bacteria. 2) Evolution - challenged with pathogenic bacteria. 3) Coevolution - challenged with pathogenic bacteria from dead worms in treatment #2. Outcrossing advantageous to a point. But sex breaks up advantageous genotypes. Not good in a constant environment.

Selection, Parasites, Environmental Change and Sex C. elegans experiment. 3 Treatments 1) Control – challenged with heat killed bacteria. 2) Evolution - challenged with pathogenic bacteria. 3) Coevolution - challenged with pathogenic bacteria from dead worms in treatment #2. Selection for successful bacteria and successful worms. Both host and pathogen are under selection – a constant arms race. Sex is beneficial in constantly generating new, potentially successful combinations.

Selection, Parasites, Environmental Change and Sex The Red Queen Hypothesis: posits that the role of sex is to preserve alleles which are currently disadvantageous, but which will become advantageous against the background of a likely future population of parasites. From Lewis Carroll’s “Alice Through the Looking Glass”, Alice finds herself hand-in-hand with the Red Queen, running faster and faster but without getting anywhere.  The Red Queen explains, "Now, here, you see, it takes all the running you can do, to keep in the same place.  If you want to get somewhere else, you must run at least twice as fast as that."

Thus Aabb and aaBB may become temporally rare. Selection, Parasites, Environmental Change and Sex Red Queen Hypothesis - Most favored changing-environment theory of sex Selection for resistance to competitor/parasite/predator #1 may favor some multi-locus genotype. E.g. AABB and aabb in a two-locus model. Thus Aabb and aaBB may become temporally rare. In the absence of resistance to competitor/parasite/predator #2, they become more successful, and more common. Selection pressures now switch for resistance to competitor/parasite/predator #2, thus favoring the two-allele combinations Aabb and aaBB. These alleles would have been lost in an asexual system because of linkage disequilibrium. But sex is able recreate these rare genotypes.

Selection, Parasites, Environmental Change and Sex

Selection, Parasites, Environmental Change and Sex Male frequency as an index of sexual females. Check 4th edition for alternate explanations. Study by Lively (1992) was observational, hence two alternate explanations are possible. 1- Trematode infection rates are higher in more dense populations of snails (true), because high host density facilitates parasite transmission. 2 – The frequency of parthenogenetic females is higher in less dense (false) populations of snails, because the real benefit of parthenogenesis is that it allows females to reproduce even when mates are hard to find.

Selection, Parasites, Environmental Change and Sex Male frequency as an index of sexual females. Infection rate by trematode parasite. Study by Lively (1992) was observational, hence two possible explanations: 1- Red Queen hypothesis - Sexual reproduction permits constant evolution by constantly recreating multilocus genotypes that may have been eliminated by selection or drift. 2 – Males are more susceptible to infections (ruled out by lab experiments).