Friday, April 28, 2017

Musical Alleles

Scott Woody, a friend and fellow science educator, asked me a few years ago to do some illustrations for a manuscript for American Biology Teacher.  That article featured a really nice analogy Scott came up with to help students understand what makes alleles dominant or recessive (Woody and Himelblau, 2013. Understanding & Teaching Genetics Using AnalogiesThe American Biology Teacher, Vol. 75, No. 9, pages 664–669. ISSN 0002-7685, electronic ISSN 1938-4211).  It has some good stuff for teaching genetics including a nice analogy for homologous chromosomes.

The thing in the paper I've used the most in my own teaching is the series of drawings about 'musical alleles' or 'musical mutations'.  The drawings here are slightly different than the ones in the paper.
Here we see two musicians playing a lovely melody.  In this analogy, the music you hear while sitting in the audience is the phenotype.  The musical score (shown above their heads) is the contains the information for how the music should be played.  In this case the both have the correct sheet music, analogous to the wildtype (WT) allele.  There are two musicians representing the two alleles of each gene found in a diploid.
In this drawing we see that a mistake happened at the sheet music printer.  One musician's sheet music is messed up forcing him to stop playing.  In genetics we would refer to this as a loss of function allele.  This image helps to show why a loss of function allele is typically recessive to wildtype...even though one musician has to stop playing the performance can continue since one musician has the correct (WT) sheet music.  In genetics we would say that the gene is in a heterozygous state (two different alleles with the dominant allele determining the phenotype).
Now we see that both copies of the sheet music are unreadable.  In this case (homozygous for the recessive loss-of-function allele) the performance has to stop.  In an organism, being homozygous for a loss-of-function allele can lead to disease or death.
In the final image we see that, yet again, the sheet music printer has made a mistake. However, the nature of the mistake is different than in the previous two examples.  Our musician is frantically trying to play all the extra notes this misprint has created.  If you were in the audience for this performance, what would you hear?  Would you hear the musician playing the correct (wildtype) part?  No!  You would hear the musician working frantically to play all those extra notes.  In this case the mistake has created a gain-of-function allele.  Gain-of-function alleles tend to be dominant to wildtype and this illustration helps to establish why that is.  (One note: students often hear "gain" and think "better" should be clear from these illustrations that, compared to wildtype, both loss-of-function and gain-of-function mutation have negative consequences.)