SB 3: Ch. 2.1 Extensions to Mendel's Laws

How to experiment with an enormous phenotypic variation pool?

• Geneticists limit the number of variables under investigation at any one time

• Mendel used pure-breeding strains of peas that had antagonistic characters of a single trait controlled by alternate alleles of only a single gene (narrowed)

• Modern geneticists use inbred populations of organisms (pure-breeding)

Complete Dominance

• If a hybrid (F1) is identical to one parent (P) for the trait under consideration, the allele carried by that parent is deemed completely dominant

• Ex: A mating between a pure-breeding white line and a pure-breeding blue line produces F1 hybrids that are white, the white allele is completely dominant to the blue allele

Incomplete Dominance

• Heterozygote has a phenotype that is an intermediate between those of the pure-breeding parents

Incomplete Dominance Biochemical Explanation

• A gene specifies a protein/enzyme required for red pigment production

• The white allele, a, does not give rise to a functional enzyme, but A does

• The amount of red pigment is proportional to the number of functional enzymes

• So, AA produces enough pigment to be fully red

• In Aa, one copy of the red allele A per cell results in only enough pigment to make pink flowers

• In aa, there is no functional enzyme so no red pigment

Codominance

• F1 heterozygotes exhibits traits of both parents

• Phenotypic and genotypic ratios line up: 1:2:1 (dominant homo, hetero, recessive homo)

Mendel’s Law of Segregation still holds

• Dominance relations are determined by proteins and their biochemical functions

• Dominance relations have no bearing on the segregation of the alleles during gamete formation

Genes can have 2+ alleles, ABO Blood types

• 3 alleles, each person carries only 2 > six possible genotypes exist with 4 different phenotypes

• Law of Segregation remain intact, the two alleles of gene separate during gamete formation

• An allele is not inherently dom/rec, this depends on its relativity to a second allele > dominance relations are unique to a pair of alleles

Genes can have 2+ alleles, Lentil seed coat patterns

• Dominance series (alleles listed in order from most dominant to most recessive)

• Marble1, Marble2, spotted = dotted, clear

• Marble1 x any other allele = a 3:1 ratio of Marble1 to any other allele, meaning it is the most dominant

• Other analogous crosses reveal 3:1 or 1:2:1 ratios, showing the phenotypic patterns are determined by different alleles of the same gene

Source of New Alleles

• Multiple alleles of an allelic series arise though chance alterations of genetic material (mutations) that spontaneously arise

Allele frequency

• Each organism carries 2 copies of every gene; calculate the number of copies of a gene in a given population by multiplying the number of individuals by 2

• # of alleles of a gene / # of gene copies = allele frequency

Polymorphic genes

• Genes with more than one common allele

• Example: Ia, Ib, and i are all common frequencies in the ABO blood type system (high frequency alleles of a polymorphic gene) making them common variants

Pleiotropy

• One gene determines multiple distinct traits

• Example: Mendel noticed that specific seed coat colors are associated with specific flower colors

• Understandable since each gene determines a specific protein/RNA that can have many effects

Pleiotropic recessive lethal allele - Mice coat color example

• Ay is pleiotropic; it affects two traits differently

1. Coat color, Ay is dominant

• A cross between AA x AyA leads to a 1:1 ratio of yellow to brown

• Since no homo AyAy are possible, this means all the yellow mice are hetero AyA and Ay is the dominant allele

2. Survival/viability trait, Ay is recessive

• A cross between AyA x AyA leads to a 2:1 ratio, not 3:1 of yellow to brown

• The missing ¼ is the AyAy homo which died before birth

• Ay is a recessive lethal allele

• A single gene (A^Y) affects two separate traits (coat color AND viability). It can have different dominance relationships for each trait

Why do recessive (lethal) alleles usually stay hidden?

• Detecting A^Y is easy because it's dominant for a visible trait (yellow coat)

• Most recessive lethal mutations don't control a visible trait in a dominant way → hidden in heterozygotes

• Lethal mutations can arise in many genes → most animals carry some recessive lethal mutations

• Homozygosity for these is rare, often caused by consanguineous matings

• Mechanism: if mutation prevents production of a crucial molecule →

  • Homozygotes: make 0% of the molecule → don't survive

  • Heterozygotes: make ~50% of wild-type amount → usually enough to sustain normal cellular processes

Delayed lethality (not in utero)

• Some mutations let homozygotes survive birth, then die later from the defect

• Example: Tay-Sachs disease

  • Caused by absence of active lysosomal enzyme Hexosaminidase A → toxic waste product accumulates in nerve cells

Transmission (passing on) of lethal alleles matters!!!!!!!!!!!!

• In recessive alleles with EARLY lethality (prenatal/childhood), the allele is passed on by heterozygote carriers since homozygotes die before reproducing (and because the lethality can be masked by a dominant allele)

• In recessive alleles with late-onset lethality, homozygotes CAN reproduce before symptoms are severe (Example: Friedreich ataxia)

• Dominant alleles with late-onset lethality can also be passed on (Example: Huntington)

• Dominant alleles with early lethality cannot be passed on (cannot be masked) THUS all such alleles must arise from new mutations

Pleiotropy in Sickle-Cell Disease - HbB gene

• Normal: HbBa HbBa, Carrier: HbBa HbBs, Diseased: HbBs HbBs

• Recessive lethality in homozygotes: heart failure from stress on circulatory system, die in childhood, adolescence, or early adulthood

• HbBs homozygotes: hemoglobin aggregates into long fibers after releasing O₂ → deforms RBC from biconcave disk → sickle shape

• Consequences: clogs small blood vessels → reduced O₂ flow → muscle cramps, shortness of breath, fatigue; sickled cells are fragile/break easily → low RBC count (anemia)

• Upside: Hbβ^S Hbβ^S homozygotes are resistant to malaria — disease can't multiply well in sickled cells (cells break down before the parasite can multiply)

Sickle-Cell disease - heterozygote advantage (balancing selection)

• Complex dominance relationship shows why the harmful HbBs allele stays common in some populations

• In malaria-endemic (native) areas:

  • HbBs HbBs = die of sickle cell

  • HbBa HbBa = die of malaria (because there are no sickle cells to prevent disease multiplication)

  • HbBa HbBs (heterozygotes) = relatively immune to both, best survival

• Result: both alleles persist at high frequency in tropical/malaria regions