Table of Contents
Gene linkage describes how genes that lie close together on the same chromosome tend to be inherited together rather than assorting independently. It refines and limits the scope of Mendel’s laws, which are strictly valid only for genes on different chromosomes or far apart on the same chromosome.
Genes on Chromosomes: Why Linkage Occurs
A chromosome is a long DNA molecule with many genes arranged linearly along it, like beads on a string. During meiosis, each pair of homologous chromosomes is sorted into gametes, and whole chromosomes (with all their genes) are moved together.
- Unlinked genes: Genes on different chromosomes (or very far apart on the same chromosome) assort independently. The allele combination in gametes follows Mendelian ratios (e.g., 1:1:1:1 in a dihybrid test cross).
- Linked genes: Genes that are physically close on the same chromosome tend to travel as a block through meiosis. Their alleles are found together in gametes more often than expected under independent assortment.
The basic idea: physical distance on a chromosome influences how likely alleles are to be separated during meiosis.
Complete vs. Incomplete Linkage
Complete linkage (no crossing over detected)
If two genes are so close together that no crossing over occurs between them in the region tested (or crossing over is extremely rare), the parental allele combinations are always transmitted together.
Example:
- Parent genotype:
AB/ab(on homologous chromosomes: one carriesAandB, the otheraandb). - With complete linkage:
- Gametes produced: only
ABandab. - Recombinant gametes
AbandaBdo not appear (or are so rare they are not detected).
In a test cross (AB/ab × ab/ab), all offspring show only the two parental phenotypes, no recombinant phenotypes.
Incomplete linkage (more typical)
In most real situations, crossing over during meiosis occasionally occurs between linked genes. This produces recombinant allele combinations.
- Parental combinations:
ABandab - Recombinant combinations after crossing over:
AbandaB
Linked genes with recombination:
- Still show more parental-type offspring than recombinant-type offspring.
- But recombinant types occur at a frequency less than 50% (often much less).
If recombination is frequent (up to about 50%), the genes seem nearly unlinked. If recombination is rare, they are very tightly linked.
Parental vs. Recombinant Types
For a pair of linked genes, in the heterozygous parent we distinguish:
- Parental (non-recombinant) combinations: Allele combinations in gametes that match those present in the parent’s original chromosomes.
- Recombinant combinations: New allele combinations not present in that parent’s chromosomes before meiosis, produced by crossing over.
Using a dihybrid AB/ab:
- Parental gametes:
AB,ab - Recombinant gametes:
Ab,aB
In progeny from a test cross, the two most frequent phenotypic classes usually represent the parental combinations, and the two least frequent classes represent recombinants.
Measuring Linkage: Recombination Frequency
Linkage is quantified using recombination frequency between two genes, defined (in a suitable test cross or mapping cross) as:
$$
\text{Recombination frequency} \ (\%) = \frac{\text{Number of recombinant offspring}}{\text{Total number of offspring}} \times 100
$$
Key points:
- 0% recombination: complete linkage (no detectable crossing over in the region).
- >0% and <50% recombination: genes are linked, with varying degrees of tightness.
- ≈50% recombination: genes are unlinked (either on different chromosomes or so far apart on the same chromosome that crossovers almost always separate them; they assort as if independent).
Note that recombination frequency never exceeds 50% in standard two-point crosses, even if multiple crossovers occur, because multiple crossovers can restore the parental arrangement and thus mask recombination events.
Coupling and Repulsion (Cis and Trans Configurations)
In a double heterozygote, the arrangement of alleles on homologous chromosomes matters for interpreting linkage.
Coupling (cis) configuration
Both dominant (or both wild-type) alleles are on the same chromosome:
- Chromosomes:
AB/ab - Here,
AandBare in coupling (on the same chromosome).
Parental gametes (more frequent): AB, ab
Recombinant gametes (less frequent): Ab, aB
Repulsion (trans) configuration
Each chromosome carries one dominant and one recessive allele:
- Chromosomes:
Ab/aB - Here,
AandBare in repulsion (on opposite homologues).
Parental gametes (more frequent): Ab, aB
Recombinant gametes (less frequent): AB, ab
This arrangement shapes which phenotypes appear most frequently in a cross, even if the recombination frequency between the two genes is the same.
Typical Test Cross Pattern for Linked Genes
A common way to detect linkage:
- Start with a double heterozygote, e.g.,
AB/ab. - Cross it to a double recessive tester,
ab/ab.
If A and B are unlinked:
- Offspring phenotypes appear in a 1:1:1:1 ratio (equal frequencies of
AB,Ab,aB,abphenotypes).
If A and B are linked:
- Two classes (parental types) are most frequent.
- Two classes (recombinant types) are less frequent.
- The proportion of recombinants gives the recombination frequency.
This pattern is the basic experimental sign of gene linkage.
Chromosome Interference and Map Distance Limits (Conceptual)
Because crossovers can occur multiple times along a chromosome:
- Multiple crossovers between two loci can go undetected if they restore the parental arrangement.
- As distance between genes increases, the chance of undetected multiple crossovers increases, so very large recombination frequencies underestimate true physical distance.
- Empirically, a recombination frequency of 1% is defined as 1 map unit or 1 centiMorgan (cM) in linkage mapping (the quantitative use of linkage, covered elsewhere).
Additionally, crossovers are not perfectly independent:
- A crossover in one region can reduce the chance of another nearby crossover; this phenomenon is called interference.
These nuances mean that linkage data need careful interpretation when building detailed genetic maps.
Linkage Groups and Chromosome Numbers
Genes that are linked to each other (i.e., show recombination frequencies less than 50% with at least some other genes in the set) form a linkage group.
Important consequences:
- The number of linkage groups in a species typically corresponds to the haploid chromosome number.
- As more genes are mapped, they can be assigned to particular chromosomes based on linkage relationships.
Thus, gene linkage was a crucial piece of evidence connecting heredity to chromosomes and allowing the construction of genetic maps along chromosomes.
Biological and Practical Significance of Gene Linkage
Gene linkage has several important implications:
- Deviation from Mendelian ratios: Linked genes do not always follow the simple dihybrid or trihybrid ratios expected under independent assortment. Recognizing linkage prevents misinterpretation of such deviations.
- Conserved trait combinations: In nature, beneficial combinations of alleles may be maintained due to tight linkage, affecting how populations evolve.
- Breeding and agriculture: Linkage can be advantageous (co-inheritance of desirable traits) or problematic (co-inheritance of a useful trait with a harmful or unwanted one). Breeders often exploit or try to break linkage using recombination.
- Human disease: Genes for certain inherited disorders can be linked to known marker genes or DNA markers. Detecting linkage between a disease and a marker is a basis for linkage analysis, used to localize and track disease genes in families.
In all these contexts, the central idea is the same: the closer two genes are on a chromosome, the more tightly their inheritance is linked, and the more often they behave as a unit across generations.