Genetics of Ribosomal Proteins: “Curiouser and Curiouser”

Lewis Carroll wrote about Alice, buthe might just as well have been referringto Calvin Bridges. As a student in T.H.Morgan’s lab, Bridges described some ofthe earliest Drosophila mutations, includingso-called Minutes, in which heterozygotesexhibited small body size and develop-mental abnormalities in tissues undergoingrapid cell division, and homozygotes werelethal [1]. At the time, it was curious howdozens of different loci could yield thesame phenotype, and even curiouser howflies multiply heterozygous at differentMinute loci were no more severely affectedthan a single Minute mutant. This mys-tery—how dozens of genes could encodesimilar but separate proliferative functionsin all cells—was solved more than 50 yearslater with the realization that mutations ofribosomal protein genes occur in almost allMinute loci [2].In this issue of PLOS Genetics, Watkins-Chow et al. [1] add to a more recentcuriosity: even though ribosomes (andribosomal protein [RP] genes) have re-mained nearly identical across more thana billion years of evolution, mutations ofRP genes in mice and in humans give riseto a surprising diversity of phenotypes.This work adds a new piece to a very oldpuzzle, and suggests the possibility that RPgenes do more than just contribute toribosomes.