How balancers work

PSzauter at PSzauter at
Sun Oct 15 14:31:15 EST 1995

On 10/14/95, yshong at asked whether there is anyone kind enough
to explain how balancers work. I am writing to explain how balancers work.

The first thing to understand is that balancers derive their name from
"balanced polymorphism". A well-known example of balanced polymorphism is the
high incidence of sickle-cell anemia in areas where malaria is endemic.
Sickle-cell anemia is caused by the Hb-S allele of the globin gene, whose
wild-type allele is denoted Hb-A. Hb-S/Hb-A heterozygotes are resistant to
malaria and therefore have a higher fitness in areas where malaria is
widespread. Hb-A/Hb-A homozygotes are susceptible to malaria and frequently
die before reproductive age, while Hb-S/Hb-S homozygotes die of sickle-cell
anemia. Selection favors heterozygotes. Yet when heterozygotes mate with each
other, they produce a 1:2:1 ratio of Hb-A/Hb-A: Hb-S/Hb-A: Hb-S/Hb-S. The two
types of homozygotes are selected against. Imagine that the selection against
homozygotes is absolute. In this case, Hb-S/Hb-A parents will lose half of
their offspring, while half will survive as Hb-S/Hb-A heterozygotes.

We would like to keep many Drosophila mutations that are lethal or sterile in
stocks that can just be pounded over without sorting out different genotypes
each generation. To keep a stock of a recessive lethal mutation on the third
chromosome, we seek to set up a balanced polymorphism using a different third
chromosome recessive lethal on the homologous chromosome. A stock of
l(3)A/l(3)B would produce inviable l(3)A/l(3)A and l(3)B/l(3)B homozygotes as
well as viable l(3)A/l(3)B heterozygotes. The problem is that recombination
will produce lethal-free recombinant chromosomes, so that we cannot be sure
that we have picked a l(3)A/l(3)B individual out of the stock if
recombination is permitted to occur.

It is possible to use chromosome rearrangements, specifically inversions, to
interfere with crossing over and to eliminate those crossover chromosomes
that do occur. An inversion is a chromosome rearrangement in which the
chromosome has been broken twice and the medial fragment has reattached in
inverted order. A chromosome sequence denoted a b c d e f might undergo an
inversion to become a e d c b f. Inversions are of two types: 1) those in
which the centromere is included in the inverted segment, called pericentric
inversions, and 2) those in which the centromere is outside of the inverted
segment, called paracentric inversions. These two types of inversions have
different consequences in meiosis. For large inversions of both types,
individuals heterozygous for the inversion and a structurally normal
chromosome will succeed in fully pairing the inversion and the normal
homologue in meiosis. This will result in an "inversion loop" in the paired
homologues (most genetics books will have a figure showing this).

If a crossover occurs within the inversion loop in a pericentric inversion,
the recombinant chromosomes will have a duplication of one chromosomal
segment and a deficiency of another (you need a figure to see this). If the
inversion breakpoints are far enough from the chromosome ends, the
duplication and deficiency will be large, and progeny inheriting the
recombinant chromosomes will die from aneuploidy.

If a crossover occurs within the inversion loop in a paracentric inversion,
one recombinant chromosome will be a dicentric (having two centromeres) and
the other chromosome will be an acentric (having no centromere). In female
Drosophila, the two meiotic divisions occur in a line, such that the
dicentric and acentric chromosomes are tied up near the two inner nuclei. One
of the two outer nuclei becomes the oocyte nucleus. Therefore, it is not
possible for progeny to inherit recombinant chromosomes from a paracentric
inversion heterozygote.

In the case of both paracentric and pericentric inversions, double crossovers
within the inversion loop will result in euploid (and monocentric)
recombinant chromosomes. If the inverted interval is small, these will be

We are now ready to build a balancer chromosome. Imagine that we can
construct a chromosome that has multiple inversions superimposed on each
other. Imagine that this chromosome also carries a recessive lethal and a
dominant marker (some dominant markers are themselves recessive lethals). An
example is the third chromosome balancer TM3 (third multiple three), which
carries multiple inversions and recessive lethals and the dominant marker
Stubble. If we cross TM3/l(3)A individuals to each other, TM3/TM3 and
l(3)A/l(3)A progeny die. The only surviving progeny are TM3/l(3)A. The
multiple inversions on TM3 not only prevent the transmission of recombinant
chromosomes to progeny, they also actually interfere with homologous pairing
and reduce the frequency of crossing over along most of chromosome three.

The only other twist is that X chromosome balancers usually do not carry
recessive lethals. If we are trying to keep an X chromosome that carries a
recessive lethal itself, there would be no X chromosomes for the males in the
stock to carry if the balancer X chromosome carries a recessive lethal.
Sometimes X chromosome balancers carry recessive female sterile mutations to
keep the balancer chromosome from taking over in the stock, but this is
usually not necessary.

Lindsley and Zimm (the Red Book) contains descriptions of the balancers that
are in common use. Most genetics books have an explanation of the mechanics
of inversions. The best explanation that I have seen is in Sturtevant and
Beadle's "An Introduction to Genetics", available from Garland Publishing. No
doubt other people responding to your post will suggest other sources. Good


Paul Szauter
pszauter at

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