Gene Linkage and Genetic Maps

Summary

This video explores the work of Thomas Hunt Morgan on X-linked genes and linkage in inheritance, focusing on experiments with fruit flies. Morgan's research showed that genes located on the same chromosome tend to be inherited together, but can occasionally separate due to a process later known as crossing over. This finding led to the development of genetic mapping by Alfred Sturtevant, who used recombination frequencies to estimate the distance between genes. Their work confirmed the chromosome theory of inheritance and laid the foundation for modern genetic mapping techniques.

Takeaways

• 🔬 Morgan's early work on X-linked genes supported the chromosome theory of inheritance.
• 🧬 Linkage in inheritance refers to the tendency of genes on the same chromosome to be inherited together.
• 🔗 Homologous chromosomes undergo crossing over during meiosis, creating recombinant chromosomes and leading to genetic variation.
• 🐝 Morgan studied fruit flies and observed how body color and wing type traits were inherited across generations.
• 👩‍🔬 Dominant traits, like gray body and normal wings, and recessive traits, like black body and vestigial wings, were used in Morgan's experiments.
• 👶 Morgan's test cross experiment with heterozygous females and recessive males showed results that pointed to linkage, but also indicated that recombination was occurring.
• 📉 The experiment produced genotypes in proportions between independent assortment and complete linkage, suggesting a process of allele recombination.
• 🔄 Crossing over during meiosis, discovered later, explained how linked genes could sometimes separate and recombine.
• 🗺 Alfred Sturtevant, Morgan’s student, developed the idea of a genetic map, linking the distance between genes with recombination frequency.
• 🧩 Sturtevant’s genetic mapping laid the groundwork for future genetic sequencing and solidified the chromosome theory of inheritance.

Q & A

What evidence first supported the chromosome theory of inheritance?

Early experiments with X-linked genes provided some of the first overwhelming evidence for the chromosome theory of inheritance.

Why is it logical that many genes on a chromosome are inherited together?

Each chromosome contains hundreds or thousands of genes, and since humans have only 23 pairs of homologous chromosomes, it is logical that genes on the same chromosome are inherited together.

What is the role of crossing over during meiosis in inheritance?

Crossing over during prophase I of meiosis produces recombinant chromosomes, which results in some genes on the same chromosome being inherited separately, rather than all genes being inherited together.

What traits were examined in Morgan’s experiment with fruit flies?

Morgan examined two traits: body color (gray body is dominant, black body is recessive) and wing type (normal wings are dominant, vestigial wings are recessive).

What were the results of the testcross in Morgan’s experiment?

The testcross showed that most offspring displayed one of two dominant genotypes, but some showed recombinant genotypes that would have been unexplainable without crossing over.

What conclusion did Morgan draw from the results of his fruit fly experiments?

Morgan concluded that the two genes were on the same chromosome, but that some process, later understood as crossing over, allowed for the rearrangement of alleles and the creation of recombinant genotypes.

What did Alfred Sturtevant contribute to genetics after Morgan's experiments?

Alfred Sturtevant developed the concept of a genetic map, using recombination frequencies to determine the distance between genes on a chromosome and their relative positions.

How does recombination frequency relate to the distance between genes on a chromosome?

Recombination frequency reflects how likely crossing over will occur between two genes. The farther apart the genes are, the more likely recombination will occur, indicating greater distance on the chromosome.

What is a linkage map and how was it created?

A linkage map is a genetic map showing the relative positions of genes on a chromosome, created by calculating recombination frequencies between different pairs of genes.

How did the work of Morgan and Sturtevant support the chromosome theory of inheritance?

Their work provided strong evidence that genes are located on chromosomes, with their positions and inheritance patterns explained by recombination and linkage, which supported the chromosome theory of inheritance.

Outlines

00:00

🔬 Introduction to Gene Linkage and Inheritance

Professor Dave introduces the concept of gene linkage by discussing early experiments on X-linked genes, which supported the chromosome theory of inheritance. He references the work of Thomas Hunt Morgan, whose experiments with fruit flies paved the way for understanding how genes on the same chromosome are inherited together. Dave explains that, although humans have only 23 pairs of chromosomes, each chromosome contains hundreds to thousands of genes, and these are generally inherited together unless crossing over occurs during meiosis, leading to recombinant chromosomes. Morgan's work with flies helped lay the foundation for this understanding.

05:05

🧬 Morgan's Experiment: Traits, Crossbreeding, and Testcross

Morgan conducted experiments with fruit flies, examining two traits: body color and wing type. Dominant traits were gray body and normal wings, while recessive traits were black body and vestigial wings. After breeding homozygous dominant and recessive flies, Morgan performed a testcross using F1 generation females and homozygous recessive males. The experimental outcome showed unexpected results: while the genes were likely linked on the same chromosome, some offspring showed recombinant genotypes, suggesting a process that allowed for rearrangement of alleles — later understood as chromosome crossover during meiosis.

🧩 Understanding Crossing Over and Genetic Recombination

Morgan's experimental findings hinted at a process that could break the linkage between genes, which we now know as crossing over during meiosis. This process allows homologous chromosomes to swap portions containing different genes, leading to recombination and new combinations of alleles. The results from Morgan's experiment with heterozygous females and homozygous recessive males confirmed that crossing over allowed for the presence of previously unexplained recombinant genotypes in the offspring.

📊 Sturtevant's Genetic Mapping and Recombination Frequency

Morgan's student, Alfred Sturtevant, took the understanding of recombination further by working on genetic mapping. He theorized that the likelihood of crossing over between two genes depended on their distance from each other on the chromosome — the farther apart the genes, the more likely they would recombine. Sturtevant developed a method to calculate the recombination frequency between genes, using it to create an early linkage map of genes along chromosomes in fruit flies. Although approximate, this effort greatly supported the chromosome theory of inheritance and laid the groundwork for future gene mapping and sequencing efforts.

Keywords

💡Chromosome theory of inheritance

This theory posits that genes are located on chromosomes, which are the structures responsible for passing genetic information during reproduction. In the video, it is referred to as an established concept that was supported by early experiments on X-linked genes and later strengthened by the work of Thomas Hunt Morgan with fruit flies.

💡Linkage

Linkage refers to the phenomenon where genes that are located on the same chromosome tend to be inherited together. In the video, linkage is discussed in the context of Morgan’s fruit fly experiments, where traits like body color and wing type did not assort independently because the genes controlling them were on the same chromosome.

💡Crossing over

Crossing over is the process during meiosis in which homologous chromosomes exchange segments, resulting in recombinant chromosomes. In the video, it is used to explain why some offspring in Morgan’s experiments had unexpected combinations of traits, as the genes for these traits were on the same chromosome but were sometimes separated by crossing over.

💡Recombination frequency

Recombination frequency measures how often crossing over occurs between two genes during meiosis. A higher recombination frequency suggests that genes are farther apart on a chromosome. In the video, this concept is used by Sturtevant to calculate distances between genes on a chromosome, leading to the creation of a genetic linkage map.

💡Testcross

A testcross involves breeding an individual showing a dominant phenotype but unknown genotype with a homozygous recessive individual to determine the unknown genotype. In the video, Morgan used a testcross to breed heterozygous flies with homozygous recessive ones, helping to reveal the effects of linkage and recombination.

💡Genetic map

A genetic map is a representation of the relative positions of genes on a chromosome, determined by recombination frequencies. In the video, Sturtevant’s work on creating a genetic map of fruit fly genes is highlighted as an early effort to understand the physical layout of genes and how crossing over affects inheritance.

💡Heterozygous

Heterozygous refers to having two different alleles for a particular gene. In the video, Morgan’s F1 generation of flies is described as heterozygous for both body color and wing type, which helped to explain the outcomes of his testcross and the role of recombination in creating new trait combinations.

💡Independent assortment

Independent assortment is the principle that genes on different chromosomes are inherited independently of one another. In the video, the possibility of independent assortment is considered for Morgan’s experiment, but since the genes for body color and wing type are on the same chromosome, independent assortment does not apply.

💡Homologous chromosomes

Homologous chromosomes are pairs of chromosomes that contain the same genes but may have different alleles. The video explains that during meiosis, homologous chromosomes can exchange genetic material through crossing over, which results in recombination and affects how traits are inherited.

💡Recessive

A recessive trait is only expressed when an individual has two copies of the recessive allele. In the video, the recessive traits discussed are black body color and vestigial wings in fruit flies. These traits only appear in flies that are homozygous recessive for the alleles governing these characteristics.

Highlights

Early experiments on X-linked genes provided strong evidence for the chromosome theory of inheritance.

Thomas Hunt Morgan's work with fruit flies helped advance understanding of inheritance and gene mapping.

Humans have 23 pairs of homologous chromosomes, and many genes on the same chromosome tend to be inherited together.

Crossing over during prophase I of meiosis leads to the recombination of chromosomes, breaking the 100% inheritance linkage.

Morgan’s experiments with body color and wing type in fruit flies examined inheritance patterns involving dominant and recessive traits.

Dominant traits in Morgan’s experiment were gray body and normal wings, while recessive traits were black body and vestigial wings.

Morgan performed a test cross by breeding F1 heterozygous females with homozygous recessive males.

If genes are on separate chromosomes, we expect a 1:1:1:1 ratio of genotypes in offspring, due to independent assortment.

If genes are linked on the same chromosome, only two genotypes should be produced, but Morgan found something in between.

Morgan’s findings led him to conclude that linked genes sometimes break apart and recombine, suggesting a process like crossing over.

Crossing over during meiosis allows homologous chromosomes to swap parts, creating new gene combinations in gametes.

Alfred Sturtevant, one of Morgan’s students, created the first genetic map by calculating gene distances based on recombination frequency.

Sturtevant reasoned that the farther apart two genes are, the more likely crossing over would cause recombination between them.

Recombination frequency helps estimate the distance between genes on a chromosome, leading to the creation of linkage maps.

Sturtevant’s mapping of fruit fly genes was an early attempt at gene mapping, which laid the groundwork for later DNA sequencing efforts.

The discovery and mapping of genes in fruit flies strongly supported the chromosome theory of inheritance.

Transcripts

Professor Dave again, let’s map some genes.

We just looked at some early experiments regarding X-linked genes, which produced some of the

first overwhelming evidence for the chromosome theory of inheritance.

This set the stage for further efforts, largely by Thomas Hunt Morgan and his flies whom we

previously introduced, so let’s take a look at what happened next.

First let’s discuss how linkage affects inheritance in general.

Humans have just 23 pairs of homologous chromosomes, but each chromosome contains hundreds or even

thousands of genes.

Thus it is logical that many or most of the genes on a particular chromosome are inherited

together.

However we now know that homologous chromosomes cross over during the prophase I of meiosis,

producing recombinant chromosomes, so it will not be the case that 100% of the genes on

a chromosome will be passed on to the offspring produced by fertilization of a particular

gamete.

This was not known by Morgan, but he did some work that set the stage for this understanding,

again by looking at flies.

In this case, two traits were examined.

Body color, and wing type.

Dominant traits are gray body and normal wings, represented by B+ and VG+, while recessive

traits are black body and smaller vestigial wings, represented by B and VG. Morgan took

flies that were homozygous dominant for both traits, and bred them with flies that were

recessive for both traits.

The F1 generation was, as expected, heterozygous for both, and thus displayed both dominant

phenotypes, so all gray with normal wings.

Then he bred females from the F1 generation with more homozygous recessive males to perform

a testcross.

Consider the possibilities.

The gametes produced by the male must contain the recessive allele for each trait.

The gametes produced by the female could be of four combinations, given the four alleles

present in the organism.

Thus we would expect the offspring to display any of the four following genotypes, resulting

in either both dominant phenotypes, just one, or just the other, or neither.

Now here’s the interesting part.

Let’s say the genes that control these traits are on separate chromosomes.

We would expect for the law of independent assortment to hold true, and each of these

four results would be equally probable, resulting in about 25% of each genotype in the F2 generation,

or a 1 to 1 to 1 to 1 ratio.

Instead, if the genes were on the same chromosome, it could have been expected that the alleles

would not separate, and only two genotypes would be possible, resulting in a 1 to 1 to

0 to 0 ratio.

The experimental results showed something in between, closer to the second option, producing

much more of the first two genotypes, but also some of the latter two.

Morgan concluded that the two genes were indeed on the same chromosome, but that some process

must sometimes break the connection between these genes and allow for rearrangement of alleles.

Later, once we discovered that crossing over occurs during meiosis, this made perfect sense.

Sometimes, homologous chromosomes can swap a portion of the chromosome containing one

gene and not the other, resulting in a new combination for the gamete that would not

have previously been expected.

This is what is happening with the heterozygous females from the F1 generation in Morgan’s

experiment, allowing for some eggs to contain recombinant chromosomes, and fertilization

of these is what accounts for the offspring with the genotypes that would have been unexplainable

without this kind of process.

Once this was understood, one of Morgan’s students, Alfred Sturtevant, worked on the

notion of a genetic map, meant to elucidate the specific loci of genes within a chromosome.

He reasoned that if crossing over can happen anywhere on the chromosome, then the farther

apart two genes are, the more likely it is that crossing over will result in recombination.

In other words, the more DNA there is in between two genes, the more likely it is that crossing

over will occur somewhere between them, thus allowing for recombination with respect to

those genes, which we can describe as a recombination frequency.

By looking at quantitative data regarding recombination frequencies for a variety of

different pairs of genes, he was able to calculate how far apart different genes are on a chromosome,

and thus in essence create a linkage map.

For instance if there is a recombination frequency of 9.5% for genes A and B, and the same for

B and C, and 17% for A and C, the only way to place these genes within the chromosome

that is consistent with this data is like this, with the genes in this order, and approximately

this far apart.

This is of course quite complicated, but it represents an early attempt to map genes,

and Sturtevant and his colleagues were quite successful in mapping many of the fruit fly

genes along the four pairs of chromosomes in the organism.

Although only approximate, it paved the way for future sequencing efforts, and corroborated

the chromosome theory of inheritance far beyond reasonable doubt.