Natural Selection and Mouse Coat Color Genetics

Coat Color Genetics

• Coat color in rock pocket mice is controlled by the melanocortin-1 receptor gene (Mc1R).
• The Mc1R gene contains two alleles: A1 for dark coloration (dominant) and A2 for light coloration (recessive).
• Possible genotypes include A1A1 (dark), A1A2 (dark), and A2A2 (light)

Natural Selection's Impact on Mouse Populations

• Dark-colored mice are more prevalent on dark lava fields.
• Light-colored mice are more common on sandy-colored rocks.
• Mismatched mice experience higher mortality rates.

Modeling Natural Selection: Allele and Genotype Frequencies

• p refers to the frequency of the dark (A1) allele, while q refers to the frequency of the light (A2) allele.
• According to the Hardy-Weinberg principle, the anticipated genotype frequencies before selection include is: A1A1 = p², A1A2 = 2pq, and A2A2 = q².
• A2A2 individuals on dark lava fields face reduced relative fitness.

Fitness Values Assignment

• Relative fitness (w) values are based on survival rates.
• w(A1A1) = 1 (dark-colored, no selection against them)
• w(A1A2) = 1 (dark-colored, no selection against them)
• w(A2A2) = 1-s (light-colored, reduced survival)
• For instance, if s=0.1, then w(A2A2) = 0.9

Selection Genotype Frequencies After

• The number of surviving individuals across genotype classes is proportional to each genotype's fitness: p²*1, 2pq*1, q²*(1-s).
• Genotype frequencies are normalized: w = p²*1+2pq*1+q²*(1-s)

Numerical Example to Illustrate Selection's Impact

• If p=0.5, q=0.5, and s=0.1,
• The normalized total fitness w¯=(0.5²*1)+(2*0.5*0.5* 1)+(0.5²*0.9) = 0.25+0.5+0.225=0.975

A1 Allele Frequency Computation after Selection Event

• The new allele frequency of A1 (p') can be calculated, p'=(p²*1)+(pq* 1)/w
• p' is found to be 0.513 (0.5/0.975=0.513. When P increases from 0.5 to 0.513, it shows A1 is increasingly over generations due to selection
• A1 allele increases over generations of selection, A1 frequency will approach 1
• A2 becomes rare in dark lava habitats and mice evolve predominantly dark coloration in these habitats over time

Frequency-Independent Selection Modes

• Fitness of a genotype is not influenced by how common or rare it is in a population.
• Frequency-dependent selection is where the fitness of a trait depends on its prevalence within a population.

Directional Selection

• One allele is consistently favored over the other.
• The favored allele approaches fixation, while the disfavored allele is lost.
• In pocket mice, the A1 allele is favored, leading to a gradual decline in the A2 allele in dark lava environments.
• Fitness ranking can either be w(A1A1)>w(A1A2)>w(A2A2) or w(A1A1)>w(A1A2)=w(A2A2).

Overdominance

• Heterozygous individuals (A1A2) have the highest fitness.
• Homozygous individuals (A1A1 and A2A2) have lower fitness.
• This leads to a stable polymorphism where both alleles are maintained.
• Sickle-cell trait in humans is an example and AS carriers are resistant to malaria, while AA (normal) is vulnerable and SS (sickle-cell disease) is harmful
• w(A1A2) > w(A1A1) > w(A2A2) or w(A1A2) > w(A2A2) > w(A1A1) is the ranking

Underdominance (Heterozygous Disadvantage)

• Heterozygotes (A1A2) have a lower fitness than both homozygotes
• One allele will go to fixation depending on initial allele frequencies.
• Chromosome inversions are an example and heterozygotes may have unbalanced gene expression leading to reduced fitness
• The ranking is w(A1A1)>w(A1A2)
• Outcome is one allele will go to fixation depending on initial allele frequencies

Stabilizing Selection on Quantitative Traits

• Selection can favor intermediate phenotypes while selecting against extreme ones, when trait is controlled by multiple genes.
• Birth weight in humans is an example where very low and very high birth weights are selected against due to higher infant mortality

Positive Frequency-Dependent Selection

• Fitness increases as a trait becomes more common.
• Leads to fixation of one allele and the loss of genetic variation, because rare traits are selected against.
• Mimicry in toxic species is an example where toxic species use warning coloration and predators learn to avoid common warning colors. Individuals with rare patterns at a disadvantage,
• Coordinated acorn production in oak trees is an example where trees produce acorns in sync to overwhelm predators.
• Snail shell coiling is where some flat snail species can only mate with individuals have the same shell coil direction, so the more common has a reproductive advantage.

Negative Frequency-Dependent Selection

• Fitness decreases as a trait becomes more common.
• Maintains genetic diversity preventing allele fixation.
• Stable polymorphism is a result as neither can fully dominate.
• Negative dependent selection maintains variation, while positive eliminates it by common traits

Selection Types Based on Timing

• Viability selection involves survival rate variations before reproduction.
• Fecundity selection stems from differences in offspring numbers produced.
• Both factors often determine fitness

Allele Frequencies Affected by Mutation

• Mutation causes one allele to change into another
• A1 will mutate to A2 with probability μ
• A2 will mutate to A1 with probability v
• These mutation events will alter the A1 and A2 allele frequencies
• Alleles are lost/gained based on probabilities, the probability of an A1 allele lost is p * μ
• The number of gained A1 alleles from A2 is = q * v
• If μ is larger, A2 will dominate
• if v is larger, A1 will dominate
• Equilibrium is reached if μ=v, and both alleles are present at equal frequencies (p=q=0.5) .

Mutation-Selection Balance

• Harmful mutations are introduced into the population.
• Natural Selection removes harmful alleles.
• the Rate at which new mutations arise is balanced out by natural selection.
• The model to setting this involves:
• Two alleles a single locus with A1 being normal and A2 being harmful
• Due to diploid, the genotypes A1A1 = (fitness = 1), A1A2 = (fitness = 1, unless dominant) A2A2 = fitness (1-s)
• Mutation will occur in one direction from, A1 -> A2 at rate μ, At equilibrium selection removes A2 as quickly as they appear
• when A2 is recessive, and with high the mutation persistent selection is strong, fewer A2 alleles will persist