Mendel's Experiments
How Mendel discovered the laws of inheritance
Gregor Mendel (1822โ1884), an Augustinian friar in Brno (now Czech Republic), performed meticulous crossing experiments with Pisum sativum (garden peas) from 1856 to 1863. He chose peas because they have easily observable, discrete traits that come in two distinct forms (tall/short, round/wrinkled, yellow/green seeds), they are normally self-fertilizing (so true-breeding lines are easy to establish), and they can be cross-pollinated artificially. He tracked seven traits and counted thousands of offspring with remarkable statistical rigor.
Mendel's results were published in 1866 but largely ignored until 1900 when three botanists (de Vries, Correns, Tschermak) independently rediscovered the same patterns and found Mendel's earlier paper. By 1900, the existence of chromosomes was known, providing a physical basis for Mendel's abstract 'factors' (now called alleles).
๐ก Punnett Squares โ Predicting Genotype and Phenotype Ratios
Punnett squares are a simple tool for predicting the frequency of different genotypes and phenotypes among offspring from a cross:
Monohybrid cross (Tt ร Tt):
T t
T: TT, Tt
t: Tt, tt
Genotype ratio: 1 TT : 2 Tt : 1 tt (1:2:1)
Phenotype ratio: 3 dominant (TT + Tt) : 1 recessive (tt) = 3:1
Testcross: To determine whether an individual with dominant phenotype is TT or Tt, cross it with a homozygous recessive (tt). If all offspring are dominant phenotype โ parent is TT. If half are dominant and half recessive โ parent is Tt. The testcross reveals unknown genotype by revealing hidden recessive alleles.
Dihybrid cross (RrYy ร RrYy): 16 possible combinations โ 9:3:3:1 phenotype ratio. Can be solved as two independent 3:1 ratios multiplied together: 9/16 round yellow, 3/16 round green, 3/16 wrinkled yellow, 1/16 wrinkled green.
L1
Law of Segregation โ alleles separate during gamete formation
The Law of Segregation (First Law): During gamete formation, the two alleles for a gene separate (segregate) so that each gamete receives only one allele. Fertilization then restores the diploid condition.
This law was derived from Mendel's monohybrid crosses. When he crossed true-breeding tall plants (TT) ร true-breeding short plants (tt), all F1 offspring were tall (Tt โ tall is dominant). When F1 plants were self-fertilized, F2 offspring were approximately 3 tall : 1 short. The short trait had 'disappeared' in F1 but reappeared in F2 in 1/4 of offspring โ proving that both alleles were present in F1 (not blended) and that they segregated cleanly during gamete formation.
The molecular basis: alleles are alternative forms of a gene at the same chromosomal locus. Homologous chromosomes separate during meiosis I, carrying their alleles to different cells โ this is the physical mechanism of segregation.
Memory trick: Law of Segregation = alleles separate during meiosis. TT ร tt โ all Tt (F1). Tt ร Tt โ 3T_:1tt (F2). The 3:1 ratio reveals segregation of one gene with two alleles.
L2
Law of Independent Assortment โ genes on different chromosomes assort independently
The Law of Independent Assortment (Second Law): Alleles of different genes assort independently of each other during gamete formation. This gives a 9:3:3:1 ratio in F2 from a dihybrid cross.
Mendel crossed plants differing in seed shape (round R vs wrinkled r) and seed color (yellow Y vs green y). F1 offspring all showed the dominant phenotypes (round, yellow โ RrYy). F2 offspring showed a 9 round yellow : 3 round green : 3 wrinkled yellow : 1 wrinkled green ratio โ exactly what is expected if the two genes assort independently (the alleles of the R gene assort independently of the alleles of the Y gene during meiosis).
The molecular basis: genes on different chromosomes (or far apart on the same chromosome) are on independently assorting homologs. When homologous pairs align at metaphase I, each pair orients randomly relative to the others โ either homolog can go to either pole. This random orientation is independent assortment.
Memory trick: Independent assortment = genes on different chromosomes sort independently. Dihybrid cross F2 ratio = 9:3:3:1. The 9:3:3:1 can be derived by multiplying two 3:1 ratios: (3:1)(3:1) = 9:3:3:1.
Dom
Dominance, recessiveness, and incomplete dominance
Dominant alleles produce their phenotype whether present in one copy (heterozygous) or two copies (homozygous). Recessive alleles only produce their phenotype when present in two copies (homozygous recessive). In heterozygotes, the dominant allele's phenotype is expressed; the recessive allele's phenotype is masked.
At the molecular level, dominant alleles often encode a functional protein; recessive alleles often encode a non-functional protein or no protein. In a heterozygote, one functional copy produces enough protein for normal phenotype (haploinsufficiency โ when one copy is not enough โ is the basis for dominant loss-of-function mutations).
Incomplete dominance: The heterozygote shows an intermediate phenotype (red flower ร white flower โ pink flower). Neither allele is fully dominant.
Codominance: Both alleles are fully expressed in the heterozygote โ different from incomplete dominance (where there is blending). ABO blood type: blood type AB individuals express both A and B antigens on their red blood cells.
Memory trick: Dominant = expressed in one copy. Recessive = needs two copies. Incomplete dominance = heterozygote is in the middle. Codominance = heterozygote shows both (AB blood type = codominant).
๐ฌ Applied Scenario โ Mendelian Genetics in Clinical Genetics
Mendelian inheritance patterns are the foundation of clinical genetic counseling:
A
Autosomal recessive disease โ cystic fibrosis. CF follows classic Mendelian autosomal recessive inheritance. Two carrier parents (Ff ร Ff) have: 1/4 FF (unaffected, non-carrier), 2/4 Ff (unaffected carrier), 1/4 ff (affected with CF). Genetic counseling for carrier couples: 25% chance of affected child per pregnancy, 50% chance of carrier, 25% chance of unaffected non-carrier. These are probabilities per pregnancy โ not cumulative (having one affected child does not reduce the probability for subsequent children).
B
Autosomal dominant disease โ Huntington's disease. Huntington's is autosomal dominant โ one copy of the mutant allele is sufficient to cause the disease. If one parent is affected (Hh heterozygote, since HH is usually lethal), each child has 50% chance of inheriting H โ 50% risk of Huntington's. The disease has late onset (typically 30โ50 years) โ affected individuals may have children before knowing they carry the allele, which is why it persists in the population.
C
Testcross in genetic counseling. A person with dominant phenotype (e.g., normal hearing when deafness is recessive) wants to know their genotype. If they have an affected sibling (dd), their parents must be carriers (Dd ร Dd). The person with normal hearing has a 2/3 chance of being a carrier (Dd) and 1/3 chance of being homozygous dominant (DD) โ using conditional probability based on their unaffected phenotype.
D
Chi-square test โ is my ratio actually Mendelian? Mendel's ratios (3:1, 9:3:3:1) are expected ratios based on probability. Actual experimental results will deviate by chance. The chi-square (ฯยฒ) test determines whether the deviation between observed and expected values is within the range of chance variation or is statistically significant (suggesting a non-Mendelian mechanism). ฯยฒ = ฮฃ[(O-E)ยฒ/E]. Compare to critical value at appropriate degrees of freedom (df = number of phenotypic classes - 1).
๐ Exam Application
Mendelian genetics is heavily tested โ master crosses, ratios, and laws:
1. Law of Segregation: Alleles separate during gamete formation. Monohybrid cross F2 โ 3:1 phenotype ratio, 1:2:1 genotype ratio.
2. Law of Independent Assortment: Genes on different chromosomes assort independently. Dihybrid cross F2 โ 9:3:3:1 phenotype ratio.
3. Dominance types: Complete dominance (3:1), incomplete dominance (1:2:1 phenotype), codominance (both alleles expressed โ AB blood type).
4. Testcross: Cross unknown dominant phenotype ร homozygous recessive. All dominant offspring โ homozygous. 1:1 dominant:recessive โ heterozygous.
5. Clinical ratios: Autosomal recessive โ carrier ร carrier โ 1/4 affected. Autosomal dominant (affected ร unaffected) โ 1/2 affected.
โ ๏ธ The Most Common Mendelian Mistakes
Mendel's ratios are PROBABILITIES, not guarantees. A 3:1 ratio means each offspring has a 3/4 chance of dominant phenotype โ it does not mean that in every family of 4 children, exactly 3 will be dominant. In small families, random variation can produce very different ratios. 'My parents are both carriers (Ff ร Ff) and I have 3 affected siblings โ does that mean my next sibling will be unaffected?' No โ each pregnancy is independent. Probability of affected = 1/4 regardless of previous outcomes (same logic as coin flips).
Genotype ratio โ phenotype ratio. From Tt ร Tt: genotype ratio is 1 TT : 2 Tt : 1 tt (1:2:1). Phenotype ratio (assuming complete dominance) is 3 dominant (TT + Tt) : 1 recessive (tt) (3:1). The genotype and phenotype ratios are different. Exams frequently ask for both โ make sure you're answering the right question.
Independent assortment requires genes on DIFFERENT chromosomes (or far apart on the same chromosome). Linked genes (on the same chromosome close together) do NOT assort independently โ they tend to stay together (linkage), violating the 9:3:3:1 ratio. Mendel happened to choose traits on different chromosomes โ which is why his results showed clean 9:3:3:1 ratios. If he had studied linked genes, he might have discovered linkage instead of independent assortment.
โ Quick Self-Test
1. State Mendel's two laws of inheritance.
2. What are the expected genotype and phenotype ratios from a monohybrid cross (Tt ร Tt)?
3. What is the purpose of a testcross?
4. What is the difference between incomplete dominance and codominance?
5. What dihybrid cross phenotype ratio does Mendel's second law predict?
Answers:
1. Law of Segregation (First Law): The two alleles for each gene segregate (separate) from each other during gamete formation, so each gamete carries only one allele for each gene. Law of Independent Assortment (Second Law): Alleles of different genes (on different chromosomes) assort into gametes independently of one another.
2. Genotype ratio: 1 TT : 2 Tt : 1 tt (1:2:1). Phenotype ratio (complete dominance): 3 dominant phenotype (TT + Tt) : 1 recessive phenotype (tt) = 3:1.
3. A testcross crosses an individual of unknown genotype (showing dominant phenotype) with a homozygous recessive individual (tt). If all offspring show dominant phenotype โ the unknown parent is homozygous dominant (TT). If half show dominant and half show recessive phenotype โ the unknown parent is heterozygous (Tt). This reveals whether a dominant-phenotype individual is homozygous or heterozygous.
4. Incomplete dominance: the heterozygote shows an intermediate phenotype between the two homozygotes (red ร white โ pink). Neither allele is fully dominant. Phenotype ratio from Rr ร Rr is 1 red:2 pink:1 white (1:2:1). Codominance: both alleles are fully and simultaneously expressed in the heterozygote โ no blending, both phenotypes present. Example: ABO blood type AB โ both A and B antigens are expressed on red blood cells.
5. A dihybrid cross (RrYy ร RrYy) produces a 9:3:3:1 phenotype ratio: 9/16 dominant for both traits, 3/16 dominant for first/recessive for second, 3/16 recessive for first/dominant for second, 1/16 recessive for both traits. This ratio demonstrates that the two genes assort independently.