Questions: Unequal Crossing Over and Gene Duplication

Question 1

During meiosis, two chromosomes each carry tandem copies of a gene (copy 1 and copy 2). Instead of aligning copy 1 with copy 1, the recombination machinery aligns copy 1 on one chromosome with copy 2 on the other. What are the products of the resulting crossing over event?

• A. Both chromosomes end up with two copies of the gene — both products gain a duplication
• B. One chromosome gains an extra copy (duplication) while the other loses a copy (deletion) — the products are reciprocal consequences of the same misalignment
• C. The misalignment is detected and repaired before crossing over occurs, producing no change
• D. Both chromosomes end up with the original single copy because the misalignment creates a deletion in both

Answer: (B)

Unequal crossing over produces reciprocal products because the physical exchange is conserved: what one chromosome gains, the other must lose. If chromosome A aligns copy 1 opposite copy 2 on chromosome B, then the segment between them is exchanged; chromosome A receives an extra copy while chromosome B loses one. This reciprocity is a direct consequence of the mechanics of crossing over — no material is created or destroyed, it is exchanged.

Question 2

Why is gene duplication through unequal crossing over evolutionarily important, rather than simply a replication error?

• A. It increases genome size, which is always advantageous because larger genomes encode more protein diversity
• B. It creates two copies where there was one, allowing one copy to accumulate mutations and acquire new functions while the original maintains its essential ancestral role
• C. It primarily produces deletions that eliminate nonfunctional pseudogenes, streamlining the genome
• D. It generates variation within a single gene, enabling that gene to simultaneously perform multiple contradictory functions

Answer: (B)

The evolutionary significance lies in the relaxation of selective constraint. A single-copy essential gene cannot tolerate most mutations — any change that impairs function is lethal or deleterious. After duplication, one copy continues to be selected to maintain ancestral function while the other is free to experiment. Over time the duplicate may evolve a new function (neofunctionalization), partition the original function (subfunctionalization), or degrade into a pseudogene. The globin, immunoglobulin, and olfactory receptor gene families all arose through this mechanism.

Question 3

The recombination machinery aligns homologous chromosomes using physical chromosome position — it finds the matching segment by locating the same chromosomal address — which prevents tandem repeats from causing misalignment.

• T. True
• F. False

Answer: False

This is the key misconception. The recombination machinery uses DNA sequence similarity, not chromosomal position, to find matching regions. It cannot 'know' that copy 1 and copy 2 are at different positions; it only sees that they share very similar sequences. When a chromosome contains tandem repeats with nearly identical sequences, the machinery can pair copy 1 on one chromosome with copy 2 on the other. This sequence-based recognition, rather than position-based recognition, is exactly what makes tandem repeats prone to unequal crossing over.

Question 4

After gene duplication, one copy is free to accumulate mutations that would be lethal in a single-copy gene, because the other copy continues to maintain the original essential function.

• T. True
• F. False

Answer: True

This redundancy is the engine of gene family evolution. When a gene exists in a single copy, purifying selection eliminates nearly all mutations that impair its function. After duplication, one copy is 'buffered' — it can tolerate loss-of-function mutations in the duplicate because the original still works. This relaxation of constraint allows exploration of sequence space that would otherwise be forbidden, and eventually produces new gene functions. The globin gene family's developmental specialization (embryonic, fetal, adult hemoglobins) is a direct product of this evolutionary freedom.

Question 5

Explain why tandem repeats make unequal crossing over more likely, and describe what determines which product receives the duplication versus the deletion.

Model answer: Tandem repeats present the recombination machinery with multiple regions of near-identical sequence. Since alignment is sequence-based, copy 1 on one chromosome can pair with copy 2 on the other ('slippage'). Crossing over at this misaligned position exchanges unequal segments. Which product receives the duplication versus deletion is determined by the direction of the slip: the chromosome that gains the segment between the two different repeat copies receives an extra copy (duplication), while the partner chromosome loses that segment (deletion). The two outcomes are always reciprocal — the same misalignment event produces both simultaneously.

This mechanism explains why large gene families are especially concentrated in genomic regions with abundant tandem repeats. The olfactory receptor loci and immunoglobulin gene clusters are both tandemly arranged and have undergone extensive unequal crossing over throughout vertebrate evolution. The same mechanism also produces copy number variants (CNVs) that underlie many human phenotypic differences and disease susceptibilities.