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Some Genes Are Transmitted to Offspring in Groups via the Phenomenon of Gene Linkage

A schematic shows the dorsal side of a black-bodied fruit fly in silhouette with its wings outstretched. The wings are smaller than normal wings and have a jagged back edge.

Black fly with short wings

Although Mendel's principle of independent assortment states that alleles of different genes will segregate independently into gametes, in reality, this is not always the case. Sometimes, alleles of certain genes are inherited together, and they do not appear to undergo independent assortment at all.

Indeed, shortly after Mendel's discoveries about inheritance patterns became widely known, numerous researchers began to notice exceptions to his principles. For example, they realized that some crosses contradicted Mendel's principle of independent assortment, because these crosses produced organisms with certain phenotypes far more frequently than traditional Mendelian genetics predicted.

Based on these findings, these scientists hypothesized that certain alleles of one gene were somehow coupled with certain alleles of another gene; however, they were not sure how this could occur. This phenomenon is now known as genetic linkage, and it generally describes an inheritance pattern in which two genes located in close proximity to each other on the same chromosome have a biased association between their alleles. This, in turn, causes these alleles to be inherited together instead of assorting independently. Genetic linkage is a violation of the Mendelian principle of independent assortment.

Independent assortment in test crosses

To understand linkage, we must first compare it to an example of independent assortment of parental gametes. The best way to generate such an example is through a dihybrid test cross, which considers two different genes during a cross between two heterozygote parents. Mendel's principle of independent assortment predicts that the alleles of the two genes will be independently distributed into gametes.

Thus, according to Mendel's principles, a dihybrid cross between two heterozygous fruit flies with brown bodies and red eyes (BbEe X BbEe) should yield offspring with nine possible genotypes (BBEE, BBEe, BBee, BbEE, BbEe, Bbee, bbEE, bbEe, and bbee) and four possible phenotypes (brown body with red eyes, brown body with brown eyes, black body with red eyes, and black body with brown eyes) (Figure 1, left). In this case, the ratio of phenotypes observed among the offspring is 9 (brown body, red eyes): 3 (brown body, brown eyes): 3 (black body, red eyes): 1 (black body, brown eyes) (Figure 1, right). This 9:3:3:1 phenotypic ratio is the classic Mendelian ratio for a dihybrid cross in which the alleles of two different genes assort independently into gametes.

A Punnett square diagram shows the resulting phenotypes and genotypes from crossing a female parent and a male parent, both with the genotype uppercase B lowercase b, uppercase E lowercase e. The genotypes of the resulting offspring produce one of four phenotypes in the following ratio: 9 flies with brown bodies and red eyes, 3 flies with brown bodies and brown eyes, 3 flies with black bodies and red eyes, and 1 fly with a black body and brown eyes.

Figure 1: A classic Mendelian example of independent assortment: the 9:3:3:1 phenotypic ratio associated with a dihybrid cross (BbEe × BbEe).

Figure Detail

In another example of Mendel's independent assortment principle, a test cross between a heterozygous BbEe fly and a homozygous bbee fly will yield offspring with only four possible genotypes (BbEe, Bbee, bbEe, and bbee) and four possible phenotypes (brown body with red eyes, brown body with brown eyes, black body with red eyes, and black body with brown eyes), as shown in Figure 2. Thus, in this case, the ratio of phenotypes observed among the offspring will be 1 (brown body, red eyes): 1 (brown body, brown eyes): 1 (black body, red eyes): 1 (black body, brown eyes).

A Punnett square diagram shows the resulting phenotypes and genotypes from crossing a female parent and a male parent. The female parent has the genotype uppercase B lowercase b, uppercase E lowercase e. The male parent has the genotype lowercase B lowercase B, lowercase E lowercase E. The genotypes of the resulting offspring produce one of four phenotypes in the following ratio: 4 flies with brown bodies and red eyes, 4 flies with brown bodies and brown eyes, 4 flies with black bodies and red eyes, and 4 flies with a black bodies and brown eyes (the ratio is one to one to one to one).

Figure 2: This 1:1:1:1 phenotypic ratio is the classic Mendelian ratio for a test cross in which the alleles of the two genes assort independently into gametes (BbEe × bbee).

Figure Detail

Exceptions to independent assortment

A schematic shows the dorsal side of two brown-bodied fruit flies in silhouette with their wings outstretched. The fly at left has normal, oval-shaped wings, while the fly at right has smaller, shriveled wings, called vestigial wings. The normal-winged fly has a genotype of either uppercase V, uppercase V or uppercase V, lowercase v. The fly with vestigial wings has the genotype lowercase v lowercase v.

Figure 3: In fruit flies, the dominant V allele produces long wings, whereas the recessive v allele produces vestigial wings. Thus, flies with the genotype VV or Vv will have long wings, and flies with the genotype vv will have vestigial wings.

In nature, some fruit fly traits like those described above assort independently, whereas others do not. As an example, consider the relationship between fruit fly body color and wing length. Here, the gene for wing length is represented by two alleles, V and v; the V allele codes for long wings, which is the dominant phenotype, and the v allele codes for short, misshapen wings (called vestigial wings), which is the recessive phenotype (Figure 3).

A schematic illustration shows the expected and observed phenotypic ratio from a cross between a heterozygous fruit fly with brown body color and normal wings and a homozygous fruit fly with black body color and vestigial wings. The phenotype is shown as an illustration of a fruit fly silhouette with its wings outstretched. The expected and observed ratio is shown as a number beside the associated phenotype. In a cross between a fruit fly with the genotype uppercase B lowercase b, uppercase V lowercase v and a fruit fly with the genotype lowercase b lowercase b, lowercase v lowercase v, the expected phenotypic ratio is 1 brown-bodied fly with normal wings to 1 brown-bodied fly with vestigial wings to 1 black-bodied fly with normal wings to 1 black-bodied fly with vestigial wings. Instead, the observed phenotypic ratio is 5 brown-bodied flies with normal wings to 1 brown-bodied fly with vestigial wings to 1 black-bodied fly with normal wings to 5 black-bodied flies with vestigial wings. This indicates that the body color gene and the wing shape gene are linked.

Figure 4: On the left is the expected phenotypic ratio of the offspring from a BbVv × bbvv cross (1:1:1:1). However, because the alleles BV and bv are linked, the observed phenotypic ratio is much different (5:1:1:5) than the expected ratio.

In order to observe the inheritance pattern associated with fruit fly body color and wing length, a test cross between a BbVv fly and a bbvv fly can be performed. The results of this cross, however, will not follow the classic 1:1:1:1 phenotypic ratio expected with independent assortment. Instead, the offspring of this particular cross will be present in a 5:1:1:5 ratio (5 brown body with long wings: 1 brown body with vestigial wings: 1 black body with long wings: 5 black body with vestigial wings). These results indicate that there is a bias toward brown body color and normal wings being inherited together (BV), as well as toward black body color and vestigial wings being inherited together (bv), from the parent with the BbVv genotype (Figure 4). Note that the parent with the bbvv genotype can only contribute bv alleles.

What is the reason for this 5:1:1:5 non-Mendelian phenotypic ratio? It turns out that the body color and wing length genes are linked, which means they are located very close to each other on the same chromosome. The consequence of this is that these gene alleles are much less likely to segregate independently into gametes. In addition, if two genes are linked in this way, then gametes are more likely to contain specific allele combinations. In this example, those combinations of alleles are BV and bv. As such, the heterozygous parent produces more BV and bv gametes than Bv and bV gametes. (Recall that the homozygous parent can only produce bv gametes.) This is why, when the BbVv fly is crossed with the bbvv fly, the resulting offspring are more likely to have BbVv and bbvv genotypes than Bbvv and bbVv genotypes, and the observed phenotypic ratio is 5:1:1:5. In fact, because the alleles do not assort independently into gametes during meiosis, Punnett squares like the ones shown in Figures 2 and 3 cannot be used to accurately predict inheritance patterns for crosses involving linked genes.

To return to the fruit fly example, linkage means that the BbVv parent is more likely to produce gametes that match those contributed by its own parents: BV and bv. Therefore, offspring with parental genotypes (BbVv and bbvv) are more common than offspring with non-parental, or recombinant, genotypes (Bbvv and bbVv) after the test cross. This means the parental genotypes and their corresponding phenotypes are observed five times more often than the recombinant genotypes and their corresponding phenotypes.

Summary

What is the lesson to be learned from the body color-wing length example? In short, whenever two genes are linked because of their location on a chromosome, their alleles will not segregate independently during gamete formation. As a result, test crosses involving alleles of linked genes will yield phenotypic ratios that stray from the classic Mendelian ratios. Also in the case of linked genes, the phenotypic ratio will show higher numbers of offspring with the parental genotypes than offspring with the recombinant genotypes.

Make your own fly

Thomas Hunt Morgan

The fly geneticist and his remarkable findings

Breeding flies is an exciting way to learn genetics. There are many possible allele combinations within a fruit fly, and you can explore them via the interactive image below. Just click on a genotype button from each category below to make your own customized fly (Drosophila melanogaster).