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The teaching and learning of macroevolutionary processes have received limited attention in the evolution education literature despite their importance in evolution acceptance and evolution understanding. This necessitates the development of pedagogical content knowledge, including best practices in curriculum and instruction, on macroevolutionary processes that support student understanding and acceptance of macroevolution. One promising approach is to consider macroevolution at the microbiological level by teaching endosymbiotic theory while capitalizing on pre-existing pedagogical content knowledge of tree thinking and bioinformatics. Here, we present a computational laboratory activity that guides students through the construction of a phylogeny based on the universal small subunit ribosomal RNA gene. The resulting phylogenetic tree demonstrates that the photosynthetic organelles of the protist Paulinella chromatophora evolved independently of the chloroplasts of plants and algae. This not only addresses the need for pedagogical content knowledge in macroevolution in an interdisciplinary and integrative fashion, but also serves as a foundation for future research into the teaching of endosymbiosis. This activity is designed for a 15–20 student introductory/intermediate biology laboratory.