Mechanism A balancer chromosome contains large inversions ([B,C,D] and [G]). Normal genetic recombination (blue X) is suppressed (red X) at these sites. Mutations without recessive lethal (or sterile) phenotype in diploid organisms can simply be bred to homozygosity and maintained  by crossing homozygotes. However, homozygotes for recessive lethal mutations are , per definition , non-viable, which necessitates maintenance of the mutation in heterozygous organisms . Crosses between heterozygotes yield a wild-type organisms , in addition to hetereozygotes and the non-viable homozygotes. To maintain a purely heterozygous line, wild-type offspring needs to be identified and prevented from mating. This can be prohibitively resource intensive , especially if long-term maintanance of the  mutation is the goal. Substituting a balancer chromosome for the wild-type chromosome homologous to the chromosome carrying the  mutation prevents the establishment of wild-type organisms in various ways. First, a balancer carries a recessive lethal mutation, which makes the organism non-viable if two copies of balancer are inherited ( ie no copy of the desired mutation). However, recombination between the balancer and the  mutated allele may result in a creation of a wild-type chromosome. To suppress recombination, balancers usually harbor multiple, nested chromosomal inversions so that synapsis between  homologous chromosomes is disrupted. If crossing over does occur, it is often unbalanced, with each resulting chromatid lacking some genes and carrying two copies of others. It can also lead to dicentric or acentric chromosomes (chromosomes with two centromeres or no centromere), which  end up breaking up and mutating or being lost  . All of these outcomes are very likely to be lethal. Finally, balancer chromosomes carry dominant  markers such as genes for green fluorescent protein or enzymes that make  pigments, which allow researchers to easily recognize organisms that carry the balancer. In the unlikely case of viable recombination, the marker may be lost thus alerting the researchers of the event. Importantly, suppression of recombination by nested inversions only occurs at the inverted intervals, while other regions (usually peri-centromeric and sub-telomeric  ) are free to recombine. Likewise, if the desired mutation is in the same locus as the balancer's recessive lethal mutation (i.e. is in strong linkage disequilibrium with it), recombination resulting in a wild-type chromosome is very unlikely, regardless of recombination suppressive inversions. In addition to simply maintaining an isolated recessive lethal (or sterile) mutation, balancer chromosomes are also used in forward genetic screens to identify such mutations. In such screens randomly mutagenized organisms carrying a balancer are crossed with each other. Offspring that carries the balancer, identified by the dominant marker, can be crossed with littermates. Any such cross that does not produce marker-negative animals is likely the result of a recessive lethal mutation in the non-balancer chromosome. Of course, only the genomic interval covered by the inversions in the balancer can be screened in this way, with recessive lethal mutations in other intervals and on other chromosomes being lost.
Mechanism A balancer chromosome contains large inversions ([B,C,D] and [G]). Normal genetic recombination (blue X) is suppressed (red X) at these sites. In diploid organisms, mutations without recessive lethal (or sterile) phenotypes can simply be bred to homozygosity and maintained stably and indefinitely by crossing homozygotes. However, homozygotes for recessive lethal mutations are by definition non-viable, because the presence of the recessive lethal allele on both chromosomal homologs causes the organism to die early in development; an organism that is homozygous for a recessive mutation that causes sterility yields essentially the same result (i.e. its genetic material cannot be passed on to progeny, even if the sterile individual itself survives to maturity). This problem forces geneticists wanting to study recessive lethal/sterile mutations to maintain the mutation in heterozygous organisms instead (in which a chromosome containing a recessive lethal/sterile mutation is complemented by a homolog that functions as wild-type at the same locus, allowing the organism to survive and reproduce more or less normally). Crosses between heterozygotes yield wild-type organisms in addition to heterozygotes and the non-viable homozygotes. To maintain a purely heterozygous line, wild-type offspring must be identified and prevented from mating. This can be prohibitively resource-intensive , especially if long-term maintanance of the recessive mutation is the goal. Substituting a balancer chromosome for the wild-type homolog of the chromosome carrying the recessive mutation prevents the establishment of wild-type organisms in various ways. First, a balancer carries its own independent recessive lethal mutation, which makes the organism non-viable if two copies of balancer are inherited ( i.e. no copy of the desired mutation). However, recombination between the balancer and the homolog containing the mutated allele may also result in the de novo creation of a wild-type chromosome. To suppress recombination, balancers usually harbor multiple, nested chromosomal inversions so that synapsis between the homologous chromosomes is disrupted. If crossing over does occur, it is often unbalanced, with each resulting chromatid lacking some genes and carrying two copies of others. The process can also lead to dicentric or acentric chromosomes (chromosomes with two centromeres or no centromere), which are inherently unstable and usually end up breaking up and mutating or being lost during subsequent mitosis . All of these outcomes are very likely to be lethal. Finally, balancer chromosomes carry dominant genetic markers such as genes for green fluorescent protein or enzymes that make visually conspicuous pigments, which allow researchers to easily recognize organisms that carry the balancer. In the unlikely case of viable recombination, the marker may be lost , thus alerting researchers to the event. Importantly, suppression of recombination by nested inversions only occurs at the inverted intervals, while other regions (usually peri-centromeric and sub-telomeric regions ) are free to recombine. Likewise, if the desired mutation is in the same locus as the balancer's recessive lethal mutation (i.e. is in strong linkage disequilibrium with it), recombination resulting in a wild-type chromosome is very unlikely, regardless of recombination suppressive inversions. In addition to simply maintaining an isolated recessive lethal (or sterile) mutation, balancer chromosomes are also useful in forward genetic screens to identify such mutations. In such screens randomly mutagenized organisms carrying a balancer are crossed with each other. Offspring that carry the balancer, identified by the dominant marker, can be crossed with littermates. Any such cross that does not produce marker-negative animals is likely the result of a recessive lethal mutation in the non-balancer chromosome. Of course, only the genomic interval covered by the inversions in the balancer can be screened in this way, with recessive lethal mutations in other intervals and on other chromosomes being lost.
R
Mutations
In diploid organisms, mutations
R
phenotype in diploid organisms
phenotypes
A
stably and indefinitely
R
, per definition ,
by definition
R
which necessitates maintenance of the mutation
because the presence of the recessive lethal allele on both chromosomal homologs causes the organism to die early in development; an organism that is homozygous for a recessive mutation that causes sterility yields essentially the same result (i.e. its genetic material cannot be passed on to progeny, even if the sterile individual itself survives to maturity). This problem forces geneticists wanting to study recessive lethal/sterile mutations to maintain the mutation
R
.
instead (in which a chromosome containing a recessive lethal/sterile mutation is complemented by a homolog that functions as wild-type at the same locus, allowing the organism to survive and reproduce more or less normally).
D
a
D
,
R
hetereozygotes
heterozygotes
R
needs to
must
R
resource intensive
resource-intensive
A
recessive
R
chromosome homologous to
homolog of
A
recessive
R
a
its own independent
R
ie
i.e.
A
homolog containing the
R
result in a
also result in the de novo
A
the
R
It
The process
A
are inherently unstable and usually
A
during subsequent mitosis
A
genetic
A
visually conspicuous
R
thus alerting the researchers of
, thus alerting researchers to
A
regions
R
used
useful
R
carries
carry