A geneticist is studying the inheritance of a trait in mice. He observes that the offspring of two parents who are homozygous recessive (gg) have a 25% chance of expressing the trait. Which of the following is the most likely genotype of the non-expressing offspring?

Core Concept

PILLAR 1 — MOLECULAR/CONCEPTUAL MECHANISM

Step-by-Step Analysis

At the molecular level, the expression of a recessive trait depends on whether a functional protein product is generated from the alleles present at a given locus. The dominant allele (G) encodes a protein—often an enzyme or structural polypeptide—that carries out its normal cellular function, such as catalyzing a step in a biosynthetic pathway or contributing to a membrane structure. The recessive allele (g) typically carries a mutation that either prevents the production of this protein entirely (a null allele) or renders it nonfunctional due to an amino acid substitution that disrupts active-site geometry, binding affinity, or tertiary folding stability. In a diploid organism, one functional copy of the gene (as in the Gg heterozygote) is generally sufficient to produce enough protein to yield the dominant phenotype—a phenomenon known as haplosufficiency. Only when both copies are the nonfunctional g allele does the trait manifest, because no functional protein is produced at all.

Why Other Options Are Wrong

Mendel's law of segregation explains the mechanistic basis for the 25% ratio: during meiosis I, homologous chromosomes—each carrying one allele at the locus—are pulled to opposite poles of the dividing cell. In a parent heterozygous at the locus (Gg), the G-bearing chromosome and the g-bearing chromosome separate into different gametes with equal probability. When two heterozygous parents each produce gametes, the four possible combinations—GG, Gg, gG, and gg—each occur with a probability of 1/4. The three genotypes GG, Gg, and gg thus appear in a phenotypic ratio of 3 dominant:1 recessive, with the genotypic ratio of 1 GG:2 Gg:1 gg.

PILLAR 2 — STEP-BY-STEP LOGIC

The critical clue in the stimulus is the 25% expression rate of the trait among offspring. A 25% (one-fourth) frequency of the recessive phenotype is the hallmark of a monohybrid cross between two heterozygous parents (Gg × Gg). Although the problem states that the parents are described as homozygous recessive (gg), the observed 25% ratio contradicts this: a gg × gg cross would yield 100% gg offspring, all expressing the trait. The most coherent explanation is that the parents are in fact heterozygous (Gg), and the geneticist's initial characterization was incorrect. From a Gg × Gg cross, the Punnett square yields 25% GG, 50% Gg, and 25% gg. The 25% who express the trait are the gg homozygotes. The remaining 75% who do not express the trait consist of two genotypic classes: GG (one-fourth of total offspring) and Gg (one-half of total offspring). Among the non-expressers, the conditional probabilities are P(Gg | non-expressing) = (1/2) / (3/4) = 2/3, and P(GG | non-expressing) = (1/4) / (3/4) = 1/3. Since 2/3 > 1/3, the most likely genotype of a randomly selected non-expressing offspring is Gg, which corresponds to option B.

PILLAR 3 — DISTRACTOR ANALYSIS

Option A (GG) tempts students who recognize that non-expressers must carry at least one dominant allele and then impulsively select the homozygous dominant genotype. The flaw is quantitative: among non-expressers, GG individuals constitute only one-third of the group, compared with two-thirds who are Gg. Selecting GG ignores the conditional probability calculation that Gg is twice as likely.

Option C (gg) traps students who take the problem statement at face value—accepting that both parents are gg—and conclude that all offspring must also be gg. This would be correct only if the parents were truly homozygous recessive, but it fails to account for the inconsistency: a gg × gg cross cannot produce only 25% expression. Choosing C requires ignoring the discordance between the stated parental genotype and the observed phenotypic ratio, reflecting a failure to apply Mendelian ratios as diagnostic evidence.

Option D (It cannot be determined) appeals to students who notice the apparent contradiction between the stated parental genotype (gg) and the 25% offspring ratio but then conclude the problem is unsolvable rather than inferring that the parental genotype must have been mischaracterized. This distractor reflects a passive approach to data interpretation. In contrast, the correct approach uses the 25% ratio as evidence to reconstruct the most probable parental cross (Gg × Gg) and then calculates the conditional genotype probabilities among non-expressers, arriving at Gg as the most likely genotype.