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AP®︎/College Biology
The chromosomal basis of inheritance
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Thomas Hunt Morgan's experiments. The fruit fly (Drosophila melanogaster) as a model system.
Key points:
- Boveri and Sutton's chromosome theory of inheritance states that genes are found at specific locations on chromosomes, and that the behavior of chromosomes during meiosis can explain Mendel’s laws of inheritance.
- Thomas Hunt Morgan, who studied fruit flies, provided the first strong confirmation of the chromosome theory.
- Morgan discovered a mutation that affected fly eye color. He observed that the mutation was inherited differently by male and female flies.
- Based on the inheritance pattern, Morgan concluded that the eye color gene must be located on the X chromosome.
Introduction
Where are genes found in a cell? Odds are, you've already heard the punchline: genes lie on chromosomes. You may have even have heard the second punchline, the one that ushered in the modern genetic era: genes are stretches of DNA that specify proteins.
However, these were not always things that you could look up on Khan Academy! When Gregor Mendel began studying heredity in 1843, chromosomes had not yet been observed under a microscope. Only with better microscopes and techniques during the late 1800s could cell biologists begin to stain and observe subcellular structures, seeing what they did during cell divisions (mitosis and meiosis).
Eventually, some scientists began to study Mendel’s long-ignored work and re-evaluate his model in terms of the behavior of chromosomes. Around the turn of the 20th century, the biology community started to make the first tentative connections between chromosomes, meiosis, and the inheritance of genesstart superscript, 1, end superscript.
The chromosome theory of inheritance
Who figured out that genes are on chromosomes? Walter Sutton and Theodor Boveri generally get credit for this insight. Sutton, who was American, studied chromosomes and meiosis in grasshoppers. Boveri, who was German, studied the same things in sea urchins.
In 1902 and 1903, Sutton and Boveri published independent papers proposing what we now call the chromosome theory of inheritance. This theory states that individual genes are found at specific locations on particular chromosomes, and that the behavior of chromosomes during meiosis can explain why genes are inherited according to Mendel’s lawsstart superscript, 2, comma, 3, end superscript.
Observations that support the chromosome theory of inheritance includestart superscript, 4, end superscript:
- Chromosomes, like Mendel's genes, come in matched (homologous) pairs in an organism. For both genes and chromosomes, one member of the pair comes from the mother and one from the father.
- The members of a homologous pair separate in meiosis, so each sperm or egg receives just one member. This process mirrors segregation of alleles into gametes in Mendel's law of segregation.
- The members of different chromosome pairs are sorted into gametes independently of one another in meiosis, just like the alleles of different genes in Mendel's law of independent assortment.
The chromosome theory of inheritance was proposed before there was any direct evidence that traits were carried on chromosomes, and it was controversial at first. In the end, it was confirmed through the work of geneticist Thomas Hunt Morgan and his students, who studied the genetics of fruit fliesstart superscript, 5, end superscript.
T. H. Morgan: Fun with fruit flies
Morgan chose the fruit fly, Drosophila melanogaster, for his genetic studies. What fruit flies may lack in charisma (depending on your taste in insects), they make up for in practicality: they're cheap, easy, and fast to grow. You can raise hundreds of them in a little bottle with sugar sludge at the bottom, and many geneticists still do this today!
Morgan's crucial, chromosome theory-verifying experiments began when he found a mutation in a gene affecting fly eye color. This mutation made a fly's eyes white, rather than their normal red.
Unexpectedly, Morgan found that the eye color gene was inherited in different patterns by male and female fliesstart superscript, 6, end superscript. Male flies have an X and a Y chromosome (XY), while female flies have two X chromosomes (XX). It didn't take Morgan long to realize that the eye color gene was being inherited in the same pattern as the X chromosome.
This may have come as a surprise to Morgan, who had been a critic of the chromosome theorystart superscript, 7, end superscript!
A "sex limited" inheritance patternstart superscript, 6, end superscript
What made Morgan think that the eye color gene was on the X chromosome? Let's look at some of his data. The first white-eyed fly he found was male, and when this fly was crossed with normal, red-eyed female flies, the start text, F, end text, start subscript, 1, end subscript offspring were all red-eyedstart superscript, times, end superscript—telling Morgan that the white allele was recessive. So far, so good, no surprises there.
But when the start text, F, end text, start subscript, 1, end subscript flies were crossed to each other, something strange happened: all of the female start text, F, end text, start subscript, 2, end subscript flies were red-eyed, while about half of the male start text, F, end text, start subscript, 2, end subscript flies were white-eyed. Clearly, the male and female flies were inheriting the trait in different patterns. In fact, they were inheriting it in the same pattern as a particular chromosome, the X.
X marks the spot
Let's see how inheritance of the X chromosome can explain what Morgan saw. Earlier, we said that female flies have an XX genotype and male flies have an XY genotype. If we stick the eye color gene on the X chromosome (writing it as a little subscript, w, plus for red and w for white), we can use a Punnett square to show Morgan's first cross:
The predictions match the start text, F, end text, start subscript, 1, end subscript phenotypes, but this set of phenotypes could also be explained by a gene that is not on the X chromosome, since all the flies were red-eyed (regardless of sex). So the real test comes when the start text, F, end text, start subscript, 1, end subscript flies are mated to make the start text, F, end text, start subscript, 2, end subscript generation:
Here is where the X makes the difference. Our Punnett square with the eye color gene on the X chromosomes correctly predicts that all of the female flies will have red eyes, while half of the male flies will have white eyes. The male flies get their only X chromosome from their mother, who is heterozygous (start text, X, end text, start superscript, w, plus, end superscript, start text, X, end text, start superscript, w, end superscript), leading to the fifty-fifty split of phenotypes.
Confirming the model
Morgan did lots of other experiments to confirm an X chromosome location for the eye color gene. He was careful to rule out alternative possibilities (for instance, that it was simply impossible to get a white-eyed female fruit fly)start superscript, 6, end superscript.
Pulling together all of his observations, Morgan concluded (correctly) that the gene must lie on, or be very tightly associated with, the X chromosomestart superscript, 7, comma, 9, end superscript. A strong confirmation of this conclusion came later, from Morgan's student Calvin Bridges. Bridges showed that rare male or female flies with unexpected eye colors were produced through nondisjunction (failure to separate) of sex chromosomes during meiosis—basically, the exception that proved the rulestart superscript, 10, comma, 11, end superscript.
Morgan also found mutations in other genes that were not inherited in a sex-specific pattern. We now know that genes are borne on both sex and non-sex chromosomes, in species from fruit flies to humans.
Want to join the conversation?
What is another definition for "hemizygous?"(17 votes)
A chromosome in a diploid organism is hemizygous when only one copy is present. The cell or organism is called a hemizygote. Hemizygosity is also observed when one copy of a gene is deleted, or in the heterogametic sex when a gene is located on a sex chromosome.(19 votes)
What if a white eyed male fruit fly (genotype XwY) is crossed with a heterozygous (i.e. with genotype Xw+Xw) female fruit fly?
Don't we get a white eyed female fruit fly?(8 votes)
You may get a white female with a XwXw genotype or a red-eyed female with a XwXw+ genotype. Morgan used this to verify his hypothesis further.
Open the hidden experiment tab under the "Confirming the model" subheading above.
Hope this helped. :)(12 votes)
Hello! I dont understand why the mutant is on the X chromosome if we said that it is defining by the sex chromosome?? if it's only for male (XY) and female has both XX, I would predict that the mutant would be on the Y chromosome, which only the male has.
thnks!(4 votes)
If the white eye trait was linked to having the Y chromosome, then you would expect that:
a) all male offspring of white-eyed males had white eyes, because they should all inherit their father's Y chromosome. In actual case they had red eyes though.
b) It would not be possible to have white eyed females, because they don't have a Y chromosome. However, in the actual case, Morgan performed experiments by crossing females which were offspring of a white-eyed male with another white eyed male, and found you can get white eyed females, so the trait is not linked to the Y chromosome. This suggests the white eyed trait is X-linked but recessive, so females only show this phenotype when they have two copies of it, and no red-eye version.
Hope that helped!(14 votes)
It is stated in the second to the last paragraph that Bridges showed more detail about Morgan's findings wherein he showed that rare male or female flies with the unexpected eye colors were produced through nondisjunction of sex chromosomes during meiosis, and since it is meiosis they should bed divided. What then is left in the cell? Does it have both X and Y? If so what about the other cell that was supposed to inherit the other sex chromosome.(3 votes)- Bridges found rare flies with surprising inheritance patterns: daughters that inherited X-linked traits (like eye colour) only from their mother, and sons that inherited their X-linked traits from their father. Due to these inheritance patterns he suggested that these daughters were XXY, and the sons were XO (unlike in humans, in drosophila, sex is determined by how many X chromosomes are present, rather than depending on the Y chromosome). His explanation was that nondisjunction had occurred during meiosis in the mother, producing egg cells with XX or no sex chromosomes. When these rare eggs were fertilized by sperm carrying either X or Y, the offspring were the XXY daughters with 2X chromosomes from the mother, and X0 sons inheriting an X from the father (those with XXX and Y0 combinations died). He also looked under a microscope and saw that these were indeed the chromosome combinations that the flies had. This work provided further evidence that inherited traits, which could be studied using the breeding experiments of genetics, are linked to physical chromosomes, that were being studied for example with dyes and microscopy.
There is more information where I read most of this, here: https://embryo.asu.edu/pages/calvin-bridges-experiments-nondisjunction-evidence-chromosome-theory-heredity-1913-1916
And here is another interesting article on the chromosome theory, Bridges' contribution, and its impact http://www.genetics.org/content/202/1/15(5 votes)
Is this a mistake in the text? Emphasis mine.
Morgan did lots of other experiments to confirm an X chromosome location for the eye color gene. He was careful to rule out alternative possibilities (for instance, that it was simply impossible to get a white-eyed female fruit fly).
By mating the F2 files [sic] from the cross above, Morgan was able to obtain white-eyed females, which he then crossed to red-eyed males. All the female offspring of this cross were red-eyed, while all the males were white-eyed.
Other comments suggest readers are getting thrown off by the contradiction. Personally I can see how a white-eyed female can be born to two parents carrying the recessive allele.(2 votes)
There is no mistake or contradiction. Note the statement preceding it: "He was careful to rule out alternative possibilities"
He ruled out that it was impossible to get white-eyed females by obtaining white eyed females.(2 votes)
- so whats the role of the cromosome y in the eye color here?(1 vote)
The role of the Y chromosome is to determine the sex. As for eye color, nothing.(4 votes)
- Couldn't we have a White EYE female fruit fly in the F3 Generation ?? PLEASE HELPP(2 votes)
The previous comment is incorrect, the logic is flawed. If a white eyed female required a white eyed female, you would have an infinite regression. You can have a white eyed female in generation 3, by mixing a red eyed female with the white eyed gene with a white eyed male.(5 votes)
Why was the idea initially controversial? What did it initially lack?(2 votes)- Gregor Mendel's work didn't explain co-dominance and so many other factors but was later found out to be the basic building block of genetics.(1 vote)
where did the first white eyed fly come from?
if there were no white eyed flys to begin with where did he get the white genotype? Please help.(2 votes)- The first mutant white allele isolated (called w1) arose spontaneously because of transposon insertion.
There are now many strains of flies with different mutations in the white gene (you can find a long list here: http://flybase.org/reports/FBgn0003996.html).
Some of these have far smaller mutations, such as just one amino acid change like described here: https://www.sciencedirect.com/science/article/pii/S0005273699000644(1 vote)
I thought it wasn't possible t obtain a white-eyed female because of the differing chromosomes in the two sexes?...(1 vote)- If you breed a homozygous red eyed female with a white eyed male, the female offspring will be heterozygous and have one copy of the mutant allele, even though the eyes are still red. Then if you breed such a female with a white eyed male, some of the female offspring will receive an X chromosome from the mother containing the white mutation, as well as the white mutant allele on the X chromosome from the father. Such females have two mutant copies and no 'normal' alleles to compensate, so would have white eyes.(2 votes)