1

Subjects Search

BIOLOGY CLASSICAL AND

MOLECULAR GENETICS SCIENCE | BIOLOGY | CLASSICAL AND MOLECULAR
GENETICS | CHROMOSOMAL BASIS OF GENETICS
Chromosomal basis of
genetics Genetic linkage & mapping
What it means for genes to be linked. How to determine
recombination frequency for a pair of genes.
Boveri-Sutton
chromosome theory
Share to Google Classroom Share Tweet
Thomas Hunt Morgan and
Email
fruit flies

The chromosomal basis of

inheritance Key points:
When genes are found on dierent
Genetic linkage & chromosomes or far apart on the same
mapping
chromosome, they assort independently and
are said to be unlinked.
Next tutorial
Sex linkage, chromosomal
When genes are close together on the same
chromosome, they are said to be linked. That
means the alleles, or gene versions, already
together on one chromosome will be
inherited as a unit more frequently than not.

We can see if two genes are linked, and how

tightly, by using data from genetic crosses to
calculate the recombination frequency.

By finding recombination frequencies for

many gene pairs, we can make linkage maps
 that show the order and relative distances of
the genes on the chromosome.

Introduction
In general, organisms have a lot more genes than
chromosomes. For instance, we humans have
roughly 19,000 genes on 23 chromosomes
(present in two sets)1 . Similarly, the humble fruit
flya favorite subject of study for geneticists
has around 13,000 genes on 4 chromosomes
(also present in two sets)2 .

The consequence? Each gene isn't going to get

its own chromosome. In fact, not even close!
Quite a few genes are going to be lined up in a
row on each chromosome, and some of them are
going to be squished very close together.

Does this aect how genes are inherited? In

some cases, the answer is yes. Genes that are
suciently close together on a chromosome will
tend to "stick together," and the versions (alleles)
of those genes that are together on a
chromosome will tend to be inherited as a pair
more often than not.

This phenomenon is called genetic linkage.

When genes are linked, genetic crosses
involving those genes will lead to ratios of
gametes (egg and sperm) and ospring types
that are not what we'd predict from Mendel's law
of independent assortment. Let's take a closer
look at why this is the case.

What is genetic linkage?

When genes are on separate chromosomes, or
very far apart on the same chromosomes, they
assort independently. That is, when the genes
go into gametes, the allele received for one gene
doesn't aect the allele received for the other. In
a double heterozygous organism (AaBb), this
results in the formation of all 4 possible types of
gametes with equal, or 25%, frequency.

Why is this the case? Genes on separate

chromosomes assort independently because of
the random orientation of homologous
chromosome pairs during meiosis. Homologous
chromosomes are paired chromosomes that
carry the same genes, but may have dierent
alleles of those genes. One member of each
homologous pair comes from an organism's
mom, the other from its dad.

As illustrated in the diagram below, the

homologues of each pair separate in the first
stage of meiosis. In this process, which side the
"dad" and "mom" chromosomes of each pair go
to is random. When we are following two genes,
this results in four types of gametes that are
produced with equal frequency.
When genes are on the same chromosome but
very far apart, they assort independently due to
crossing over (homologous recombination). This
is a process that happens at the very beginning
of meiosis, in which homologous chromosomes
randomly exchange matching fragments.
Crossing over can put new alleles together in
combination on the same chromosome, causing
them to go into the same gamete. When genes
are far apart, crossing over happens often
enough that all types of gametes are produced
with 25% frequency.
When genes are very close together on the same
chromosome, crossing over still occurs, but the
outcome (in terms of gamete types produced) is
dierent. Instead of assorting independently, the
genes tend to "stick together" during meiosis.
That is, the alleles of the genes that are already
together on a chromosome will tend to be
passed as a unit to gametes. In this case, the
genes are linked. For example, two linked genes
might behave like this:

Now, we see gamete types that are present in

very unequal proportions. The common types of
gametes contain parental configurations of
allelesthat is, the ones that were already
together on the chromosome in the organism
before meiosis (i.e, on the chromosome it got
from its parents). The rare types of gametes
contain recombinant configurations of alleles,
that is, ones that can only form if a recombination
event (crossover) occurs in between the genes.

Why are the recombinant gamete types rare?

The basic reason is that crossovers between two
genes that are close together are not very
common. Crossovers during meiosis happen at
more or less random positions along the
chromosome, so the frequency of crossovers
between two genes depends on the distance
between them. A very short distance is,
eectively, a very small "target" for crossover
events, meaning that few such events will take
place (as compared to the number of events
between two further-apart genes).

Thanks to this relationship, we can use the

frequency of recombination events between two
genes (i.e., their degree of genetic linkage) to
estimate their relative distance apart on the
chromosome. Two very close-together genes will
have very few recombination events and be
tightly linked, while two genes that are slightly
further apart will have more recombination
events and be less tightly linked. In the next
section, we'll see how to calculate the
recombination frequency between two genes,
using information from genetic crosses.

Finding recombination
frequency
Let's suppose we are interested in seeing
whether two genes in the fruit fly (Drosophila) are
linked to each other, and if so, how tightly linked
they are. In our example, the genes are3 :

The purple gene, with a dominant pr+ allele

that specifies normal, red eyes and a
recessive b allele that specifies purple eyes.

The vestigial gene, with a dominant vg+

allele that specifies normal, long wings and a
recessive vg allele that specifies short,
"vestigial" wings.
If we want to measure recombination frequency
between these genes, we first need to construct
a fly in which we can observe recombination.
That is, we need to make a fly that is not just
heterozygous for both genes, but where we
know exactly which genes are together on the
chromosome. To do so, we can start by crossing
two homozygous flies as shown below:

[What do homozygous and heterozygous mean?]

Image modified from "Drosophila melanogaster," by Madboy74

(CC0/public domain).

This cross gives us exactly what we need to

observe recombination: a fly that's heterozygous
for the purple and vestigial genes, in which we
know clearly which alleles are together on a
single chromosome.

Now, we need a way to "see" recombination

events. The most direct approach would be to
look into the gametes made by the heterozygous
fly and see what alleles they had on their
chromosomes. Practically, though, it's much
simpler to use those gametes in a cross and see
what the ospring look like!

To do so, we can cross a double heterozygous fly

with a tester, a fly that's homozygous recessive
for all the genes of interest (in this case, the pr
and vg alleles). The purpose of using a tester is
to ensure that the alleles provided by the non-
tester parent fully determine the phenotype, or
appearance, of the ospring. When we cross our
fly of interest to a tester, we can directly "read"
the genotype of each gamete from the physical
appearance of the ospring.

Image modified from "Drosophila melanogaster," by Madboy74

(CC0/public domain).

Below, we can see a modified Punnett square

showing the results of the cross between our
double heterozygous fly and the tester fly. Four
dierent types of eggs are produced by a double
heterozygous female fly, each of which combines
with a sperm from the male tester fly. Four
dierent phenotypic (appearance-based) classes
of ospring are produced in this cross, each
corresponding to a particular gamete from the
female parent:

Image modified from "Drosophila melanogaster," by Madboy74

(CC0/public domain).

The four classes of ospring are not produced in

equal numbers, which tells us that the purple and
vestigial genes are linked. As we expect for
linked genes, the parental chromosome
configurations are over-represented in the
ospring, while the recombinant chromosome
configurations are under-represented. To
measure linkage quantitatively, we can calculate
the recombination frequency (RF) between the
purple and vestigial genes:
 Recom
Recombination frequency (RF) =
Total o

In our case, the recombinant progeny classes are

the red-eyed, vestigial-winged flies and the
purple-eyed, long-winged flies. We can identify
these flies as the recombinant classes for two
reasons: one, we know from the series of crosses
we performed that they must have inherited a
chromosome from their mother that had
undergone a recombination event; and two, they
are the underrepresented classes (relative to the
overrepresented, parental classes).

So, for the cross above, we can write our

equation as follows:

151 + 154
RF = 100% =
1339 + 1195 + 151 + 154

The recombination frequency between the

purple and vestigial genes is 10.7%.

Recombination frequency and

linkage maps
What is the benefit of calculating recombination
frequency? One way that recombination
frequencies have been used historically is to
build linkage maps, chromosomal maps based
on recombination frequencies. In fact, studying
linkage helped early geneticists establish that
chromosomes were in fact linear, and that each
gene had its own specific place on a
chromosome.

Recombination frequency is not a direct measure

of how physically far apart genes are on
chromosomes. However, it provides an estimate
or approximation of physical distance. So, we can
say that a pair of genes with a larger
recombination frequency are likely farther apart,
while a pair with a smaller recombination
frequency are likely closer together together.

Importantly, recombination frequency "maxes

out" at 50% (which corresponds to genes being
unlinked, or assorting independently). That is,
50% is the largest recombination frequency we'll
ever directly measure between genes. So, if we
want to figure out the map distance between
genes further apart than this, we must do so by
adding the recombination frequencies of multiple
pairs of genes, "building up" a map that extends
between the two distant genes.

Comparison of recombination frequencies can

also be used to figure out the order of genes on
a chromosome. For example, let's suppose we
have three genes, A, B, and C, and we want to
know their order on the chromosome (ABC?
ACB? CAB?) If we look at recombination
frequencies among all three possible pairs of
genes (AC, AB, BC), we can figure out which
genes lie furthest apart, and which other gene
lies in the middle. Specifically, the pair of genes
with the largest recombination frequency must
flank the third gene:

Recombination frequencies are based on those for fly genes v, cv, and
ct, as given in D. C Bergmann4 .

[Why don't the recombination frequencies add up?]

By doing this type of analysis with more and

more genes (e.g., adding in genes D, E, and F
and figuring out their relationships to A, B, and C)
we can build up linkage maps of entire
chromosomes. In linkage maps, you may see
distances expressed as centimorgans or map
units rather than recombination frequencies.
Luckily, there's a direct relationship among these
values: a 1% recombination frequency is
equivalent to 1 centimorgan or 1 map unit.

Is map distance always the same as

recombination frequency? Sometimes, the
directly measured recombination frequency
between two genes is not the most accurate
measure of their map distance. That's because, in
addition to the single crossovers we've
discussed in this article, double crossovers (two
separate crossovers between the two genes) can
also occur:

Double crossovers are "invisible" if we're only

monitoring two genes, in that they put the
original two genes back on the same
chromosome (but with a swapped-out bit in the
middle). For example, the double crossover
shown above wouldn't be detectable if we were
just looking at genes A and C, since these genes
end up back in their original configuration.

Because of this, double crossovers are not

counted in the directly measured recombination
frequency, resulting a slight underestimate of the
actual number of recombination events. This is
why, in the example below, the recombination
frequency directly measured between A and C is
a bit smaller than the sum of the recombination
frequencies between A-B and B-C. When B is
included, double crossovers between A and C
can be detected and accounted for.

By measuring recombination frequencies for

closer-together gene pairs and adding them up,
we can minimize "invisible" double crossovers
and get more accurate map distances.

[References]

Ask a question...

Questions Tips & Thanks Top Recent

could you show a three point crossover?
9 votes Comment Flag
6 months ago by Carmen Herrera

Is 50% always the highest recombination frequency or

could it theoretically be exceeded if a small enough
population of flies were used?
5 votes Comment Flag
7 months ago by Nye Rhys Potter

Recombination frequency will never exceed 50%.

This is because of double-crossing over, which
restores the parental arrangement.
4 votes 2 comments Flag
6 months ago by Shane Taylor Wilson

Show all 2 answers Answer this question

how would the recombination frequencies calculations

dier if it were three dierent genes, instead of two, and
you were to find the recombination frequencies between
all the genes??
1 vote 1 comment Flag
about a month ago by 0627050

what percentage or map units is considered close? is

anything lesser than 50 map units considered close??
1 vote Comment Flag
 24 days ago by Muhammad Irfan Mohd Isa

How can you create a tester to test if the trait is sex-

linked? Eg. White eyed fruit fly could only be produced as
a male, wouldn't it be impossible to breed a tester?
1 vote Comment Flag
5 months ago by Geo Mallett

A cross between a female fly that is heterozygous for

white eyes and a male that is white-eyed could
produce female progeny with white eyes, because
the mother makes two kinds of gametes: one X
chromosome that encodes red eyes, and one X
chromosome that encodes white eyes. If the gamete
encoding for white eyes is fertilized by the X
chromosome from the father, then female white-eyed
flies result.
1 vote Comment Flag
5 months ago by City Face

How do you know where to map the first gene and then
work from there in mapping the other genes? (So you map
the gene that has the highest recombination frequency
first right?) also if marker alleles are potentially linked to
disease genes (haplotype) and segregate throughout a
family how do you know which marker to use to look for
the disease gene? How would you know where the
disease gene was and therefore which markers to look at,
woukd you need to have an idea of the chromosome/ part
of the (more)
1 vote Comment Flag
3 months ago by Shama Uddin

To answer your first question, it is not possible in

these experiments to know the absolute locations of
genes. The recombination frequencies allow
inference of relative positions of the genes to each
other, which you can then map onto the
chromosome, but you don't need to map the first pair
to a particular position. For example if the
recombination frequency between A and B is 45%,
you know they lie further out toward the ends of the
chromosome. By repeating the experiment with
dierent genes, (more)
1 vote Comment Flag
3 months ago by Ryan Hoyle

crossing over between chromosomes which leads to

recombination occurs at random chromosomal locations
.what does random means here ?
1 vote Comment Flag
27 days ago by Jahangir Alam

In maize coloured endosperm (C) is dominant over

colourless (c) and full endosperm (R) is dominant over
shrunken (r). When a dihybrid of F1-generation was test
crossed it produced four phenotypes in the following
percentage
Coloured and Full = 45%
Coloured - Shrunken = 5%
Colourless - Full = 4%
Colourless- Shrunken =46%
From these data what would be distance between the two
non allelic genes?
1 vote Comment Flag
about a month ago by Mruga

Will there be more cM in heterochromatic regions?

1 vote Comment Flag 2 months ago by Tara

How much of this should we know for SAT Biology?

I did find a question in which the F2 generation had a
ratio of 3:1 dominant to recessive, and the question asked
about the position of the two genes controlling these
traits. Is there a simple way we could solve similar
questions?
0 votes Comment Flag
2 months ago by farahgebril01

No you do not need to know any of this for the SAT

biology. You do not have to know gene distances
you do not know to know morgans experiment.
When in doubt just know it exists. This is
predominantly for AP bio.
1 vote Comment Flag
2 months ago by crazymonkey844
 The chromosomal basis of inheritance

About
Our mission is to provide
a free, world-class News

education to anyone, Our team

anywhere. Our interns

Our content specialists

Khan Academy is a 501(c)
Our leadership
(3) non-profit company.
Our supporters
Donate or Volunteer
Careers
today!
Internships

Contact

Help center

Support community

Share your story

Press

Download our apps

iOS app

Android app

Subjects
 Subjects

Math by subject

Math by grade

Science & engineering

Computing

Arts & humanities

Economics & finance

Test prep

College Admissions

Change language

2017 Khan Academy Terms of use Privacy notice