MBIO161 Genetics 7-12

29 January 2025: Inheritance I

• Mendellian inheritance

  • Discrete genetic characters

    • Those that show a limited number of distinct categories

    • Phenotype = the outward, physical appearance of a trait.

      • A  character = a heritable feature (ex. flower colour)

      • A  trait = a variant of each character (ex. purple or white)

    • Genotype = the coded, inheritable information in an organism’s DNA

    • An allele is one specific form of a gene that differs from other alleles by one or a few bases only and occupies the same locus (site/location) as other alleles of the gene

      • Organisms can be homozygous at a locus (alleles both the same) AA or aa or heterozygous (two different alleles) 

        • Ex.  Aa

      • Alleles can be dominant (A) or recessive (a)

      • More than 2 alleles can be present for one locus in the population,  but only 2 alleles can be present at any one locus in any diploid individual

      • In diploids:

        • Each sperm or egg is haploid can carry only one allele:

          • Heterozygotes (Aa) produce two gamete types

          • Homozygotes (AA, or aa) produce only one

    • Punnet squares/genetic cros

      • 1. Monohybrid cross (one [mono] character only)

        • 3:1 ratio

        • Mendel’s Law of Segregation:

          • The two alleles at any one locus in a diploid individual separate (segregate) during gamete formation. Each one has equal probability of ending up in the resulting gametes (50%)

            • Here a Pp parent can produce both P gametes, and p gametes

            • In this case P(purple) is dominant and p(white) is recessive

      • 2. Dihybrid cross (two characters-ex. color and shape)

        • 9:3:3:1 ratio

        • Mendel’s Law of Independent Assortment

          • Each pair of alleles at any one locus segregates independently of other pairs of alleles at other loci

            • Widely thought that Mendel’s laws meant recessive traits would disappear over time

  • Mendel

    • 19th century ‘blending theory’  was popularly held view

• Hardy-Weinberg

  • Hardy & Weinberg (1908) demonstrated that Mendel’s laws predict that allele frequencies will stay constant under certain conditions

    • Brief overview of Mendellian inheritance

      • In a population, lots of individuals of all possible genotypes are mating at random. In the case of Mendel’s discrete characters (here seed shape – round R or wrinkled r)

        • Some are RR and produce only R gametes

        • Some are Rr and produce both types

        • Some are rr and produce only r gametes

      • The probability of two alleles meeting is the product of their frequencies in the population.

      • If 80% of the alleles in the population are R, then they have a probability of meeting of 0.8 x 0.8 = 0.64

      • Genotype frequencies:

        • RR: 9/14 = 0.64

        • Rr: 4/14 =  0.28

        • rr:  1/14 =  0.07

      • Allele frequencies

        • 28 alleles (14 individuals each with 2)

        • 22 of these are R

        • Frequency of R is 22/28 = 0.8

        • R = 0.8

        • r = 0.2

    • Gametes make new genotypes in predictable frequencies

      • The overall population and the chances of R and r meeting according to their starting frequencies in the population

        • Allele frequencies stay constant (Hardy-Weinberg)

    • Allele frequencies in populations are variable

      • We describe H-W expectations when there are just two alleles at any one locus (here R and r). However, in reality there may be more than 2 alleles in the population. The principles of H-W expectations still apply, they just get more complex to work out

    • Are dominant alleles always more common than recessive ones?

      • No

        • Ex. eye color

          • Eye colour largely determined by the OCA2 gene (although other genes are also involved)

            • Brown (B) dominant over “not-brown” (b)

    • Allele and genotype frequencies aren’t constant over all successive generations

      • In reality often gametes do not truly meet ‘at random”

      • We can test whether gametes are meeting at random in populations by genotyping them, quantifying allele frequencies and asking whether they meet with the frequencies the Hardy-Weinberg model predicts

    • The H-W model makes some important assumptions:

      • Infinite population size

      • Random mating

      • No mutations

      • No selection

      • Equal allele frequencies among males and females

    • If populations deviate from H-W expectations, then we say that they are not in H-W equilibrium and it indicates that one or several or these assumptions are not being met 

      • The H-W model is an important null model to test population genotype and allele frequencies against: Is evolution happening?

  • Mendellian genetics + Darwin’s “Origin” → Neo-Darwinism / The Modern Synthesis (Fisher, Haldane, Wright)

    • Led to a raft of ‘crossing’ experiments using a wide range of organisms to test Mendel’s Laws

      • That gave us further insight into the variety of complex ways that genes can work and interact

        • But these all still follow Mendel’s laws

• Examples of more complex genetic effects

  • Types of dominance

    • Codomiance

      •  Both alleles in the genotype are seen in the phenotype

        • Ex. red/white spotted cows 

          • Both alleles (red and white) are present in the physical presentation (phenotype)

    • Incomplete dominance

      • Only one allele in the genotype is seen in the phenotype

        • A dominant allele does not completely mask the effects of a recessive allele

          • Red (dominant) x white (recessive) flowers → pink flowers 

  • Lethal gene

    • A gene where particular allele combinations lead to the death of an individual; can be either dominant or recessive

  • Pleiotropic genes 

    • Those that have >1 distinguishable effect

      • Ex. gene for Marfan syndrome causes a host of symptoms

  • Sex-linked genes

    • X-linked: 

      • More common in males due to there only being one X chromosome 

        • Ex. color blindness

      • Females are more likely to be carriers but not present with any symptoms

    • Y-linked: 

      • Much rarer

      • Only occurs in males

  • Recessive epistatic genes/inhibting genes

    • When present, it blocks expression of alleles at locus 1

      • Ex. Coat color in Labs

31 January 2025: Inheritance II

• Non-Mendellian inheritance

  • Genetic linkage (Punnett & Bateson, 1905)

    • When alleles at separate loci are inherited together and thus do not obey Mendel’s law of independent assortment

      • Alleles from loci that are located close together on the same chromosome are less likely to be ‘split’ apart by crossing over and recombination

        • Such loci are described as being linked

          • Ex. Drosophila eye colour and wing length

  • Cytoplasmic inheritance (Carl Correns, 1925)

    • Some traits are inherited from organellar DNA

    • 2 observations:

      • Natural selection works to increase frequency of genes that have beneficial phenotypic effects

      • Genes ‘cooperate’ with other genes within an organism to ensure their own transmission to descendants

        • Intragenomic conflict:

          • When genes or alleles evolve ways of transmitting themselves preferentially over others

  • Meiotic drive

    • Any process which causes some genetic variants to be over-represented in the gametes which are formed during meiosis

      • Ex. the T locus in mice

        • TT normal long tails, Tt short tails, tt sterile

        • 90% of Tt individuals transmit t and not T to their offspring

          • t is a segregation distorter

      • These kinds of effects can also be brought about by intracellular parasites

        • Ex. the bacterial genus Wolbachia

  • B chromosomes

    • B chromosomes (= ‘supernumerary’ or ‘accessory’ chromosomes) can also be transmitted in germline cells more frequently than expected from Mendelian inheritance expectations, and can accumulate ‘selfishly’

      • They have been found in all major groups of animals and plants.

• The determination of continuous characters

  • Polygenic/quantitative characters

    • Individual heritable characters are often controlled by groups of several genes

    • Variation is continuous or quantitative (‘adding up’) - also called quantitative inheritance

  • Continous characters

    • Controlled by several loci, each with small effect

    • Each one follows Mendelian inheritance patterns

    • Discrete traits tend to be generated by single loci, continuous traits by many loci

    • The substitution of one allele for another is often undetectable

    • The environment often has a substantial influence

    • Different genotypes can produce the same phenotype

      • Ex. Kernel color in wheat

        • The same phenotype can be generated from many different genotypes

  • Phenotypic plasticity

    • When a genotype expresses different phenotypes depending on the environment

      • These kinds of effects are well known, even if not yet fully understood, ex. in field of human medicine:

        • Some genotypes are more prone to developing classes of disease from exposure to environmental hazards than others

          • Ex. certain genotypes may be more prone to addiction, autoimmune disorders, etc, based on their environment  

        • Also in animals:

          • Ex. non-swarming grasshoppers exhibit density-dependent phenotypic plasticity reminiscent of swarming locusts

    • If different genotypes have different kinds of phenotypic plasticity, we call the effect a genotype-environment interaction

  • Phenotypic variation

    • Total phenotypic variation is due to:

      • Environment

      • Genetics

      • Interaction between genes and environment

    • This combination of genotype and environment in many continuous/quantitative characters tends to lead to an even greater, ‘smoother’, distribution of phenotypes

      • But only in quantitative genetic traits

11 February 2025: Natural Selection

• Artificial selection

  • Standing genetic variation 

    • Presence of alternative forms of a gene (alleles)

  • Evolution is limited by standing variation until new mutations accumulate

• Heritability and fitness

  • Heritability

    • Heritability is the proportion of phenotypic variation (VP) that is due to genetic variation (VG), where VE = phenotypic variation due to the environment

      • VP = VG + VE + VGxE

        • H2 = VG/VP

          • Broad sense heritability: the fraction of the variance that is potentially due to genetic causes

            • Note – it does not measure whether a trait has a genetic basis: no heritability does not mean the trait has no genetic basis

    • So, characters that have high heritability can be easily selected for:

      • Ex. after 40 generations of artificial selection

  • For natural selection to operate, there needs to be trait heritability but also variation in fitness:

    • The average genetic contribution of a particular genotype or phenotype to the next generation

      • Selection typically acts on small differences in fitness:

        • Fitter genotypes spread through the population while less-fit genotypes gradually decline

          • And remember that it can only act on heritable variation

      • Humans have used artificial selection to enhance traits that are beneficial (for food or other resources):

        • Ex. corn, watermelon, tomatoes, etc.

      • In nature, it is the environment that affects relative fitness

• Detecting natural selection

  • Experimental manipulation

    • Guppies evolve to have larger, but fewer, offspring in the presence of a predator that predominantly eats juveniles

  • Trends associated with environmental change

    • Mimic behavuoirs

  • Inter-specific comparisons

    • Competition and constraint drove Cope's rule in the evolution of giant flying reptiles

  • Changes in allele frequencies

    • Ex. mosquitoes and being resistant to DDT over many generations

      • Allele frequencies changed

• Modes of selection

  • Directional

    • Occurs when one extreme phenotype is favored over other phenotypes

      • Ex. large beaks are favoured much more over smaller beaks in finches after a drought 

  • Stabilizing 

    • A type of selection that  favors average traits and selects against extreme traits; traits don’t change much over time

      • Ex. galling flies are attacked by birds and parasitoid wasps, so ones with less coloring are favoured over ones that have more coloring 

  • Disruptive

    • Occurs when extreme traits (both sides) in a population are favored over intermediate traits

      • Ex. Lazuli bullings are either very dull or very bright, there’s almost no individuals in between (males tend to be very bright, females very dull

        • Sexual selection

11 February 2025: Selection and Drift

• The maintenance of polymorphism (variations in DNA sequences that are present in a significant portion of a population) though/the reason why selection doesn’t lead to uniformity:

  • i. Balancing selection

    • Maintains a balance or equilibrium between different morphs or alleles

      • Can be assessed at the phenotype or genetic level

    • Two main kinds of balancing selection:

      • Negative frequency-dependent selection

        • Examples:

          • Left handedness in humans: general population: male ~13%; female ~10%

            • Higher in interactive sports, acts as an advantage 

          • Ex. Scale-eating cichlid fish Perissodus microlepis

        • Apostatic selection

          • A type of selection that occurs when predators preferentially eat common prey over rare prey

            • Rare phenotypes have an advantage

            • More likely to be ignored by predators

        • Hosts and parasites (or competitors) are in an arms race

          • Constant adaptation by the parasite to overcome the host’s immune defenses

          • Co-evolution among hosts evolving new defenses

        • Red Queen hypothesis

          • Have to keep evolving in order to stay in the same place

        • Common genotypes are more easily overcome by the parasite

        • Rare genotypes are less-frequently encountered, and eventually spread through the population

          • Rarity an advantage: negative frequency-dependent selection

        • Note that positive frequency selection also occurs,

          •  Ex. mimicry

      • Heterozygote advantage

        • Resistant rats:

          • Structurally different enzyme, not affected by Warfarin less efficient in Vitamin K recycling

            • i.e. there is a cost to resistance

  • ii. Spatial and temporal effects

    • But other circumstances can also maintain polymorphisms

      • Spatial variation in selection

        • Rock pocket mouse

      • Temporal variation in selection

        • Ex. Biston betularia

• Genetic drift

  • Regardless of selection, not all individuals will successfully breed into the next generation just by chance

    • In populations that are very large, this is unlikely to affect the frequencies of alleles significantly

    • In small populations genetic drift can very rapidly erode genetic diversity

  • Alleles can randomly reach fixation in small populations very quickly through drift

  • Fixed or lost alleles

    • The probability that an allele is fixed or lost is related to its starting frequency and the size of the effective population

    • Most new mutations are lost to drift (they are at very low frequency) but the average time that will take will vary according to the effective population size

  • Drift can have a profound effect if populations go through bottleneck or founding events

    • Ex. bottlenecks in northern elephant seals or founder events (when a new population is established from a small number of individuals drawn from a large ancestral population)

      • Such events can lead to isolated populations having quite different genetic variation than others

        • Drift can result in deleterious (alleles that reduce fitness in an organism) alleles reaching high frequencies

12 February 2025: The evolution of sex

• Why does sex exist?

  • Sexually reproducing organisms:

    • Different varieties of organisms produce different, specialized cells by meiosis: gametes

      • These combine by fertilization to form a new individual

    • Gametes can be identical (isogamy)

    • Often, they are not (anisogamy) and the type with the smaller cell is the male

  • Asexual reproduction:

    • Binary fission

      • Ex. bacteria, protists & some unicellular fungi

    • Budding 

      • Ex. baker’s yeast, hydra, anemone

    • Vegetative reproduction

      • Plants

    • Spores 

      • Ex. some fungi, some algae

        • Note that many fungi produce spores sexually as well as asexually

    • Fragmentation 

      • Ex. lichens, annelids, sea stars, plants

    • Parthenogenesis

      • Ex. rotifers, insects, reptiles, amphibians

  • Sex is costly

    • Usually requires two separate sexes

    • Usually need to spend time finding partner (or gamete)

    • May need to fight other members of your own sex to access a mate

    • Need to persuade partner to mate (courtship)

    • Need to produce gametes, most of which are wasted

    • Risk catching diseases

    • Your own alleles are diluted 50% with those of partner!

  • Two fold cost of sex

    • Sexual females have half as many daughters as do asexual females

    •  If a sexual and asexual female produce the same number of offspring… …the asexual population grows at twice the rate

  • Sex is common

    • It has been around for about 1.2 billion years

    • Now most life forms are sexual

      • Though most organisms (Bacteria & Archaea) are asexual

    • Sex works

      • Experiments show that sexual lineages usually outcompete asexual lineages in the long term

  • Potential advandatges of sex

    • Leads to unique combinations of alleles:

    • Alleles segregate independently into gametes

    • Fertilization combines alleles from different lineages

    • Crossing over shuffles alleles between chromosomes

    • Three possible advantages:

      • Generates genetically diverse offspring

      • Eliminates costly mutations quickly

      • Allows beneficial alleles to combine

        • Muller’s ratchet: without recombination, deleterious mutations will accumulate

          • Remember that most mutations are detrimental to the organism

  • Asexual vs. sexual reproduction

    • Asexual reproduction:

      • Requires less energy

      • No costly non-reproducing sex

      • Quicker

      • Offspring are clones of the parents

    • Sexual reproduction:

      • Requires more time and energy

      • Two-fold cost of producing males

      • Offspring are genetically diverse

      • Mutations are more easily purged

      • Beneficial mutations can combine more easily

• How can we define the sexes?

  • Macroscopic differences between male and female

    • Sexual dimorphism 

    • Differences between gametes

      • Sex determination systems

        • Ex. ZW system

          • Occurs in birds, some fish

          • Females ZW, males ZZ

      • Environmental sex determination

        • Ex. temperature-dependent

        • Egg temperature

          • 23-27 °C, mostly male

          • ~30 °C, female

        • Hormone mediated

    • Reproductive parasites

      • Ex. Wolbachia

        • Intracellular parasites/endosymbionts

          • Arthropods, nematodes

        • Transmission via host egg, but not sperm

    • Infection-induced sex determination

      • Armadillidium vulgare

        • Isopod crustacean

        • Androgenic gland

          • Male hormone ↑ by Z chromosome

          • Male hormone ↓ by W chromosome

            • (∴ ZW = ‘female’)

    • Feminisation by Wolbachia

      • Degradation of gland

      • Suppression of ‘male’ gene

    • Hermaphrodites

      • Frequent in invertebrates, occasional in vertebrates, usual in plants

        • Seqeuntial

          • Ex. clownfish

        • Simultanous

          • Ex. garden snail

  • Differences between gametes

    • Cells that ‘fuse’ = fertilization

    • Morphologically different:

      • Heterogamy (anisogamy)

        • Larger produced by female (egg/ovum)

        • Smaller produced by male (sperm/spermatozoan)

    • Carry one set of chromosomes (haploid)

      • Gametes contain mix of alleles from parents due to independent assortment and recombination

    • Isogamy

      • Gametes can look the same

  • Inhertiance from one parent

    • Mitachondrial DNA (mtDNA)

      • Uniparental (non-Mendelian) inheritance

        • input bias

        • Unequal cytokinesis

        • Selective destruction of mitochondria in gametes

        • Disappearance of mtDNA

        • Sperm organelles fail to enter egg

        • Selective destruction of mitochondria in zygotes

      • Mitochondria are maternally inherited

        • Usually

    • Nuclear DNA is inherited from all ancestors

    • Contribution of one gamete much greater than other:

      • Ovum, large cytoplasm: nucleus ratio

        • Ex. 105 mitochondria (or orders of magnitude more)

    • Selective silencing

      • Chlamydomonas reinhardtii

        • Plus (+) mating type

          • mtDNA destroyed

    • Why uniparental inheriatance

      • BIparental inheritance leads to cytoplasmic mixing (heteroplasmy)

        • Competition between mitochondria that are genetically different

          • Smaller genome → more rapid replication

            • ∴ Competes more effectively

            • But smaller genome may compromise ATP generation for the cell 

      • Uniparental inheritance

14 February 2025: Sexual selection

• History of the concept

  • Why do some sexes (usually males) have elaborate traits that appear detrimental to survival?

    • Darwin (1871) proposed two explanations:

      • Traits are useful in male-male combat

      • Traits preferred by females ‘secondary sex(ually selected) traits’

        • Darwin viewed sexual selection as a separate process from natural selection

    • This doesn’t explain some important phenomena:

      • Female solicitation and multiple mating

      • Higher reproductive output for females that have multiple mates

      • Male sperm limitation

      • Monogamy

      • Polyandry

      • Male mate choice

      • Sex role reversal

    • Parental investment theory (Trivers 1972):

      • The sex which exhibits less parental investment (not necessarily the male) will have to compete to mate with the opposite sex

      • In species where both sexes invest heavily, they should be mutually choosy

        • Choosiness by one sex leads to sexual dimorphism:

          • Ex. peacocks, mallard ducks, etc

      • Parental investment is any investment made by the parent that benefits their current offspring at the expense of future offspring.

        • Cost of producing gametes, parental care, etc

• Intra-sexual selection

  • Definition: members of the same sex compete for mates

    • In many systems, males fight for exclusive mating access to female group (evolution of weaponry: price is high but rewards can be enormous)

      • Consequence: intense intrasexual section

        • Has led to the evolution of a raft of interesting alternative male strategies - ex. sneaker males

• Evolution of male choice 

  • Selection of the mate is dependent on their ‘attractiveness’

    • In most cases, females choose among competing males

      • BUT – there are many exceptions

        • AND – even in the more common cases, males are also choosy

  • Evolution of inter-sexual selection

    • Direct phenotypic benefits

      • Choosy individuals receive direct benefits from their mates

        • Food, breeding territory, parental care, etc.

          • Ex. Male damselfish defend permanent territories

      • Females choose mates on the basis of their territory (e.g. size, structure).

      • Female choice directly affects egg survival

      • Ex. Tiger moths

        • Males produce spermatophores ~11% of their body weight

        • Contain sperm, nutrients, and pyrrolizidine alkaloids

        • Female gains:

          • Produce 32 more eggs for each additional mating due to nutritional ‘gift’

          • Additionally, alkaloids incorporated into eggs protect them from predators

      • But females are choosy even when they gain nothing but gametes: indirect or genetic benefits. How have these evolved? (they often seem very costly to male carriers)

    • Sensory bias hypothesis

      • Female mating preferences may be by-products of selection on sensory systems; males evolve traits that “exploit” these biases

        • Ex. Xiphophorus genus: swordtails and platyfish

          • Swordlessness is the primitive state

          • Female platyfish prefer conspecific males with artificial swords

          • A pre-existing bias for swords?

    • Fisherian runaway

      • Fisher (1930): male ornamentation is the result of female preference for males with the most exaggerated ornaments

        • Initial female preference is arbitrary

        • Strong female choice for the male ornament results in runaway sexual selection, leading to the further exaggeration of the trait

        • Preference for the trait (in females) becomes genetically linked to expression of the trait (in males)

        • Continues until the costs imposed by natural selection balance the benefits of sexual selection.

      • Runaway selection drives traits past their natural-selection optimum

    • Sexy son hypothesis

      • Closely related to Fisherian runaway selection

      • Assumes an indirect benefit to female choice due to the attractiveness of their sons

        • Females that mate with an attractive male will produce attractive sons

          • Their fitness will be increased as a result of their sons’ higher mating success

    • Indicator traits

      • Handicap principle (Zahavi 1975)

        • The handicap principle: reliable signals must be costly to the signaller

          • → Only high-quality individuals can afford the cost of the signal.

        • If signals are cheap, all individuals can display them, so they provide no information to the receiver

        • Hamilton-Zuk Hypothesis (1982)

          • A special case of the Handicap Principle

            • Sexual ornaments are indicators specifically of parasite and disease resistance

              • Ex. intestinal nematodes adversely affect male secondary sexual characters

      • Runaway Selection vs Handicap Principle

        • Runaway selection:

          • Genes for attracting females only

          • Signal and preference for signal become linked

          • No positive relationship between signal and genetic quality

          • Signal negatively or uncorrelated with condition

        • Handicap principle:

          • Genes for survival/reproduction, not just attractiveness

          • Not necessary for signal and preference to be linked

          • Signal positively associated with genetic quality

          • Signal may be positively associated with condition

    • The lek: assembly areas for displaying to attract females

      • Leks occur when males are unable to defend females or resources

        • Different than harems, where several females congregate near one male for reproduction 

      • So why do males do it?

        • Males settle where encounter rate is high (hotspots)

        • Aggregate to reduce predation

        • Aggregate to increase attraction rate

        • Females prefer aggregates for mate choice

      • The lek paradox

        • Strong skew in male reproductive success

        • A few generations of mating should eliminate most genetic variation

        • Yet females remain choosy

        • What maintains variability in attractiveness?