We use maps every day to figure out how to walk from home to school, and then
from school to soccer practice. Scientists also use maps to navigate
through the enormous amount of DNA in a cell-- 3 billion base pairs in humans.
The DNA is organized into several long strands called chromosomes. Within each
chromosome are genes, regions of the DNA that specify traits, like eye color
or blood type. But how are these traits ordered in the DNA, which genes are
close together and which are far apart? To answer this question, you need a map.
Back in the early 1900s, two scientists named Alfred Sturtevant and Thomas Hunt
Morgan, made the first map of genes in the fruit fly, Drosophila. But before
we get into Morgan and Sturtevant's research and its implications, let's
quickly review what was known at the time about how traits are inherited.
Fifty years earlier, Gregor Mendel, a monk who performed experiments on pea
plants, noted that traits, like whether the plant's flowers were white or
purple in color, or whether the peas were round or wrinkled in shape,
assorted independently. If you breed a white flower, round pea plant with a
purple flower, wrinkled pea plant, you can get any combination of these traits
in the offspring plants.
Thomas Hunt Morgan studied two traits in Drosophila: eye color, which could
be either red or white, and the length of the wings, long or short. If you
bred a white eyed, long winged fly with a red eyed, short winged fly, the
offspring almost always resembled one of the parents. They were either white,
long or red, short. Unlike the experiments from Mendel, these traits
were not assorting independently. Instead, these traits were, what he
called, linked to each other. So what was going on? Morgan guessed that the
genes coding for these traits must lie on the same chromosome. So when sperm
or eggs are formed the two genes from the same parent always went into the
same sperm or egg cell, they stayed linked together. In contrast, if they
were on different chromosomes, then the genes and their traits should sort
independently, as described by Mendel.
Interestingly, however, Morgan also saw that occasionally some of the offspring
from the white-long to red-short breeding had a different appearance
from the parents. He would sometimes get white-short or red-long offspring
flies. How could this have occurred if the genes are linked? Morgan's
hypothesis, which we now know is correct, was that maternal and paternal
chromosome pairs can exchange pieces of DNA with each other. This exchange is
called crossing over or recombination. If the crossover point occurs in
between the gene for eye color and the gene for wing length, new combinations
of traits, like white-short or red-long, could be found in the
offspring. So what does this have to do with maps? Morgan's student, named
Alfred Sturtevant, reasoned that the frequency of crossover could be used to
infer the approximate distance between genes on a chromosome. And if we know
distance between genes, we can make a map.
How did he do this? Let's look at the chromosome pair below. If the genes for
eye color and wing length are very far apart from each other on the chromosome,
it is very likely that recombination could occur at a spot in between the
two genes. This means it would be likely to get new combinations of
offspring that were distinct from their parents. In contrast, if the eye color
and wing length genes were very close to each other on the chromosome, it is
much less likely that the chromosomes would cross over in between the two
genes. So in this case, we would not expect to get many offspring that had a
different appearance from the parents. Then Sturtevant analyzed six different
genes that he knew were all found on the same chromosome. He determined the
percentage of crossover events that occurred by looking at specific
features in the offspring when he bred different types of flies.
The higher the percentage of crossing over, the farther apart the two genes
were on the chromosome, and the lower the percentage of crossing over,
the closer the two genes were. By this method Sturtevant deciphered the order
of the six genes on the chromosome and approximately how far apart each one
was from the other. This amazing finding established that chromosomes
are linear and that the genes are organized within each chromosome in
defined positions.
The Sturtevant-Morgan findings have had long term implications. Scientists have
used similar genetic mapping strategies to pinpoint the location of, and then
clone, a gene of interest. On a grand scale, scientists constructed genetic
maps of thousands of genes in Drosophila and humans, and then took
this concept one step further to sequence the entire 3 billion base pair
human genome.
The genome sequence is the ultimate high resolution map. Even now,
scientists use genetic mapping to find a connection between a genetic disease
that runs in families and gene mutations that might underlie the
disease.