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.