The observation that provides the strongest evidence that genes are NOT composed of DNA, according to the Protein Hypothesis, is:
DNA is composed of smaller subunits than are proteins.
This statement implies that if genes were composed of DNA, there would be a question of how DNA can encode for the vast diversity and complexity of proteins, which are made up of larger and more varied subunits (amino acids). The Protein Hypothesis posits that proteins are the primary molecules of biological function, suggesting that the information needed to produce proteins must reside in something other than DNA.