HER - Genetic Linkage [LESSON]

Genetic Linkage

In general, organisms have a lot more genes than chromosomes. For instance, we humans have roughly 19,000 genes on 23 chromosomes (present in two sets). Similarly, the fruit fly has around 13,000 genes on 4 chromosome pairs. The consequence? Each gene isn't going to get its own chromosome. In fact, quite a few genes are going to be lined up in a row on each chromosome, and some of them are going to be squished very close together. Does this affect how genes are inherited? In some cases, the answer is yes. Genes that are sufficiently close together on a chromosome will tend to "stick together," and the versions (alleles) of those genes that are together on a chromosome will tend to be inherited as a pair more often than not. This phenomenon is called genetic linkage. When genes are linked, genetic crosses involving those genes will lead to ratios of gametes (egg and sperm) and offspring types that are not what we'd predict from Mendel's law of independent assortment.

Let's take a closer look at why this is the case by watching the Linkage Gene Inheritance video below: 

When genes are on separate chromosomes, or very far apart on the same chromosomes, they assort independently. That is, when the genes go into gametes, the allele received for one gene doesn't affect the allele received for the other. In a double heterozygous organism (AaBb), this results in the formation of all 4 possible types of gametes with equal (25%) frequency.

Why is this the case? Genes on separate chromosomes assort independently because of the random orientation of homologous chromosome pairs during meiosis. Remember that homologous chromosomes are paired chromosomes that carry the same genes, but may have different alleles of those genes. One of the pair is the maternal chromosome and the other is the paternal chromosome of that set. The homologous pairs separate during meiosis I, and their lineup is random each time.  So, the maternal chromosome may be on the left one time and then on the right during another round of meiosis.  This results in a 25% chance of each gamete because independent assortment does a really good job of shuffling up the chromosomes. 

When genes are located on the same chromosome but really, really far apart, they still assort independently due to the high likelihood of crossing over occurring which separates the alleles. We still see a 25% chance of each gamete forming.

However, if the genes are closer together on the same chromosome, there’s a much higher chance of alleles traveling together into the same gamete.  We see in the image that gamete AB and ab have a much higher chance of forming than aB or Ab.

 

Now, we see gamete types that are present in very unequal proportions. The common types of gametes contain parental configurations of alleles—that is, the ones that were already together on the chromosome in the organism before meiosis. The rare types of gametes contain recombinant configurations of alleles, that is, ones that can only form if a recombination event (crossover) occurs in between the genes.

Why are the recombinant gamete types rare? The basic reason is that crossovers between two genes that are close together are not very common. Crossovers during meiosis happen at more or less random positions along the chromosome, so the frequency of crossovers between two genes depends on the distance between them.

 

Recombination Frequency 

If one parent is doubly heterozygous (AaBb) and the other is doubly homozygous recessive (aabb), then we can determine the frequency of recombination by this calculation:

In fruit flies, brown body is dominant over black body. Normal wings are dominant over dumpy wings. Calculate the recombination frequency using a BbNn fly with a bbnn fly using the following data. Data: Brown, normal - 300; Brown, dumpy - 154; Black, normal - 162; Black, dumpy - 318

Answer: Recombination frequency = 154 + 162 x 100/934 Recombination frequency ~ 33.8 %

Linkage Maps

Recombination frequency is not a direct measure of how physically far apart genes are on chromosomes. However, it provides an estimate or approximation of physical distance. So, we can say that a pair of genes with a larger recombination frequency are likely farther apart, while a pair with a smaller recombination frequency are likely closer together. Recombination frequency is between 0% (right next to each other) and 50% (assorting independently – either far apart on the same chromosome or on different chromosomes)

Comparison of recombination frequencies can also be used to figure out the order of genes on a chromosome. For example, let's suppose we have three genes, A, B, and C, and we want to know their order on the chromosome (ABC? ACB? CAB?) If we look at recombination frequencies among all three possible pairs of genes (AC, AB, BC), we can figure out which genes lie furthest apart, and which other gene lies in the middle.

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