What
types of genome maps are there?
The two main kinds of genome maps are known as genetic-linkage maps
and physical maps. Just like the various types of earth maps, they contain
different types of information and have different strengths and weaknesses.
For example, on a political map of the United States, Colorado appears
as a featureless rectangle that gives no hint to the state's dramatic
scenery. On a physical map, Colorado is a stunning collection of mountain
peaks, high plateaus, and open prairienatural features that don't
tell you anything about where the state's boundaries are.

Image of crossing over occuring in
chromosomes |
Genetic-linkage mapping. Genetic-linkage maps illustrate the
order of genes on a chromosome and the relative distances between those
genes. Originally, these maps were made by tracing the inheritance of
multiple traits, such as hair color and eye color, through several generations.
Genetic-linkage mapping is possible because of a normal biological
process called crossing over, which occurs during meiosisa type
of cell division for making sperm and egg cells. During one stage of
meiosis, chromosomes line up in pairs along the center of a cell, where
they sometimes "stick" to each other and exchange equivalent pieces
of themselves. This sticking and exchanging is called crossing over,
and is a relatively common event: on average, a chromosome pair undergoes
crossing over about 1.5 times during the formation of each sex cell
in humans.
For example, imagine a man who has one chromosome with brown-eye and
brown-hair genes, and another chromosome with blue-eye and blonde-hair
genes in his cells. Usually, his sperm cells will have either brown-eye
and brown-hair genes, or blue-eye and blonde-hair genes. But if crossing
over occurs, the man will produce one sperm cell with brown-eye and
blonde-hair genes, and another with blue-eye and brown-hair genes.
In short, crossing over produces chromosomes with new combinations
of genesand offspring, called recombinants, with new combinations
of traits not seen in either parent. Generally the closer two genes
are on a chromosome, the less likely they are to be separated by crossing
over.
This means that traits that are inherited together most often are probably
influenced by genes that are close to each other on a chromosome. On the
other hand, traits that are inherited together less often are probably
influenced by genes that are farther apart. Thus, by following several
traits through generations and recording how often recombinants occur,
one can map the relative position of corresponding genes.
A. H. Sturtevant, then a student at Columbia University, made the first
genetic-linkage map of fruit fly genes in 1913decades before scientists
even knew that genes are made of DNA. He found, for example, that leg
length was inherited with eye color more often than with wing length,
and that wing length was inherited with eye color more often than with
leg length. Thus, he concluded, the gene for eye color must be between
the genes for wing length and leg length in the fruit fly genome.
But because the frequency of crossing over varies at different places
in the genome, these early genetic-linkage maps only gave the relative
positions of genes, not their physical locations in the genome or
their actual distances, in DNA base pairs, from each other. In addition,
the maps were based on the inheritance of traits, not genes, and this
limited the possible landmarks to characteristics that were visible or
measurable in some way.
Today, scientists make genetic-linkage maps by tracing the inheritance
of certain DNA sequences the same way they once traced the inheritance
of visible traits. The genome contains many places where the DNA sequence
varies from person to person (where I have AAC you have AAG, for example).
These sequence variations, or polymorphisms, make up many of the landmarks
on modern genetic-linkage maps and enable scientists to anchor genes to
their true physical locations in the genome.
Physical mapping. Physical maps, by contrast, always give the
physical, DNA-base-pair distances from one landmark to another.
In the late 1970s, scientists developed new and efficient ways of cutting
the genome up into smaller pieces in order to study it. Around the same
time they made the first physical maps by using the overlapping DNA
sequences at the ends of the genome pieces to help them keep track of
where the pieces came from. (The process had a lot in common with the
assembly step of genome sequencing.) In other words, a physical map
was simply an ordered set of DNA pieces.
This worked okay for a while, but then more and more scientists started
getting interested in the genome, and they were all cutting it up in
different ways and building physical maps from different sets of DNA
pieces. The scientists couldn't share information with each other, because
they each had maps written, in effect, in a different language. Moreover,
the landmarks they were using weren't necessarily uniquethat is,
a landmark could appear in more than one place in the genome, so finding
a landmark didn't necessarily tell you where you were.
Today, genome scientists use landmarks known as STSs to help them find
their way around the genome. Each STS, or "sequence-tagged site," is
a unique DNA sequenceone that is found in only one place in the
genomeand is a few hundred base pairs long. Some STSs are parts
of genes, but an STS can come from anywhere in the genome as long as
it is unique.
No matter how you cut up a genome, STSs will tell you where the pieces
belong. For example, once an STS has been added to the genome map, you
can figure out whether any piece of DNA contains that STS landmark.
If it does, you know exactly where in the genome that piece of DNA belongs.
Scientists began to use STSs to construct maps in the late 1980s. Thus,
physical maps have evolved from an ordered set of DNA pieces (which
can be used only by people who have the same set of pieces) into a set
of landmarks based on unique DNA sequences (which can be used by any
scientist the world over).
What
are the maps like that are being made now? What will the genome map
be like when it is done?
The genome's cartographers are now making maps that combine features
of both genetic-linkage and physical maps. For example, new methods
of genetic-linkage mapping based on polymorphisms enable scientists
to place landmarks at the proper physical locations on the chromosomes.
Meanwhile, some STSs on physical maps are parts of genes and thus give
the sort of information that appears on genetic-linkage maps.
As mapping techniques advance, scientists try to create maps with more
landmarks that are more closely, evenly, and accurately spaced. But in
contrast to DNA sequencing, which has become increasingly automated, genome
mapping still can only be accomplished by experienced scientists. And
even the most expert mapper may run into difficulties finding the desired
number and type of landmarks with the desired spacing. This means that
although maps keep improving, the work is slow and there is still a long
way to go.
It's almost as difficult (and arbitrary) to define a "complete" genome
map as it is to define a "complete" genome sequence. One definition
of "complete" is a map that includes the sequence and location of all
of an organism's genes. Such maps currently exist for more than 150
organisms, most of them viruses with small genomes.
. . . .
. . . . . . . . .
. . . . . . . .
Updated on January 15, 2003
|