Drosophila melanogaster is a great model system for studying mutations, many of which are recessive lethal. You might be wondering: How is it possible to stably maintain a recessive lethal mutation in a fly stock? Wouldn’t the mutant allele be lost over time, as it is gradually bred out with each successive generation? Not to worry — balancer chromosomes are an amazing tool used to reliably maintain recessive alleles (or any other gene of interest) across generations. But what exactly is a balancer chromosome?
Balancer chromosomes are specially modified to allow for stable maintenance of mutant fly stocks
A balancer chromosome has a few key properties that make it possible to reliably maintain a gene of interest (such as a mutation) over time:
- Multiple inverted DNA sequences throughout its length, which suppresses recombination with its homologous partner chromosome (the one containing the gene of interest). This means that no crossing over occurs during meiosis, so any mutant alleles of interest stay in their place on the chromosome.1
- A dominant marker allele, and a recessive lethal allele. The dominant marker allele let’s you know exactly which flies carry the balancer, and the recessive lethal allele prevents homozygous balancer lines from forming (which would eliminate your gene of interest).1
Below is an example of two flies carrying the FM7 balancer chromosome, which carries a dominant marker allele for bar-shaped eyes. The male fly on the left has a more pronounced eye phenotype because, unlike the female on the right, it doesn’t carry a second X chromosome to compensate.
Commonly used balancer chromosomes
Below is a list of some of the most commonly used balancer chromosomes. Notice that each code name refers to certain key features of the balancer.
- FM7a (1st multiply-inverted 7a): X chromosome balancer, typical markers include y, wa, sn, B1
- FM7c (1st multiply-inverted 7c): X chromosome balancer, typical markers include y, sc, w, oc, ptg, B1
- CyO (Curly derivative of Oster): 2nd chromosome balancer, typical markers include Cy (Curly), dp (dumpy; bumpy notum), pr (purple; eye color), cn2 (cinnabar; eye color)
- SM6a (2nd multiply-inverted 6a): 2nd chromosome balancer, typical markers include al, Cy, dp, cn, sp
- TM3 (3rd multiply-inverted 3): 3rd chromosome balancer, typical markers include Sb, Ubxbx-34e (bithorax; large halteres), e, Ser
- TM6B (3rd multiply-inverted 6B): 3rd chromosome balancer, typical markers include AntpHu, e, Tb (Tubby; physically shorted 3rd instar larvae and pupae)
Maintaining a recessive lethal mutation with a balanced first chromosome
The best way to wrap your mind around balancer chromosomes is to study a real-life example. Below is a sample genetic cross that makes use of a balanced first chromosome (i.e. X chromosome) to maintain a recessive lethal allele of mys (myospheroid) from parents to offspring.1 P denotes the parental generation, and F1 denotes the first familial generation.
In the P generation, females carrying mys on the X chromosome, balanced with FM7, are crossed to males carrying one copy of the FM7 balancer. In the F1 generation, males carrying the mys mutation die (because they carry only one X chromosome, and it contains a lethal allele), and females carrying two copies of the FM7 balancer are sterile, owing to its intentionally engineered recessive sterile mutation. As a result, the only viable offspring remaining are those with identical genotypes to the parental generation. The balancer chromosome worked as intended!
How to order balancer chromosome fly stocks
The Bloomington Drosophila Stock Center carries dozens of different single-balancer chromosome fly lines (covering the X through 4th chromosomes) as well as fly lines carrying multiple balancers. You can start browsing their balancer collection here.
References
- Roote J and Prokop A. How to design a genetic mating scheme: A basic training package for Drosophila genetics. G3. 2013;3(2):353-8. doi: 10.1534/g3.112.004820