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The Chromosome Theory of
Inheritance
In 1902, Walter Sutton, along with Theodor
Boveri proposed a theory that chromosomes
were the carriers of Mendel’s factor (later
called as genes). They found a close similarity
between transmission of hereditary traits and
behavior of chromosomes while passing from
one generation to the next. The two
investigators suggested that segregation and
independent assortment are properties of
chromosomes.
Soon thereafter, genetic investigations with
several organisms revealed that certain
genes were not transmitted according to
the law of independent assortment. When
studied together in matings, these genes
seemed to segregate as if they were
somehow joined or linked together. Further
investigations showed that such genes were
the part of the same chromosome and they
were indeed transmitted as a single unit
We now know that most
chromosomes consist of very large
number of genes. Genes that are the
part of the same chromosome are
said to be linked and demonstrate
linkage in the genetic crosses.
Because the chromosome, not the
gene is the unit of transmission
during meiosis, linked genes are not
free to undergo independent
assortment. Instead, the alleles at all
loci of the one chromosome should,
in theory, be transmitted as a unit
during gamete formation.
Thomas Morgan began his work
with the fruit fly Drosophila
melanogaster around 1910. He was
awarded Nobel Prize in Medicine in
1933 for his research in genetics
The fruit fly came into its own as a laboratory
model when scientists in the early twentieth
century discovered Drosophila was easy to
keep, feed and breed, and by the 1920s fruit
flies were the subject of extensive
experiments in heredity in the labs of Nobel
Prize-winner T. H. Morgan and elsewhere. As
its popularity as a model increased, data on
all aspects of fly biology, from molecular
genetics to learned behaviors, burgeoned.
In one cross, Morgan considered body color
G B b b
V v v
F B b b b
V v
v v
Grey body,
Black body,
long wings
vestigial wings
According to independent assortment,
this should produce 4 phenotypes in a
1:1:1:1 ratio.
1 : 1 : 1 : 1
Ifthe genes are completely linked,
we should expect to see a 1:1:0:0
ratio with only parental phenotypes
among offspring because no other
combinations are possible.
Black body,
Grey body,
vestigial wings
long wings
50% 50%
Although most of the offspring did
have the parental phenotype, some
of the flies were genetic
recombinants, having phenotypes
different from the parents.
R =Number of recombinants
observed/total offspring scored ) X 100
Gene mapping
• Linkage provides a way to map genes on
chromosomes. Until modern gene mapping
techniques linkage was the only way to do this.
Even today linkage is important when used with
other techniques to determine where on
chromosomes certain genes are, especially for
genes which have not been well studied and for
understanding the mode of transmission for many
genetic disorders.
Genetic-linkage mapping is possible
because of a crossing over.
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.
Genetic-linkage maps.
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.
A. H. Sturtevant, then a student at Columbia
University, made the first genetic-linkage
map of fruit fly genes in 1913—decades
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
unique—that 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
sequence—one that is found in only one
place in the genome—and 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.
Scientistsbegan 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).