Rachel
Marie Isaac

Phylogenetic Reconstruction of the Evolution of One Instance of Tyrosine Kinase Activity Life Sciences

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Rachel Marie Isaac

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A key question in evolutionary biology is the role of chance and contingency in evolutionary processes. This question has remained unanswered because most traits evolved only once. However, tyrosine kinase (TK) activity has evolved multiple times independently, allowing for comparative analysis of the substitutions that caused TK activity in each instance. In this study, the evolutionary trajectory of TK activity was determined by constructing a phylogenetic tree of kinases with and without TK activity and then reconstructing ancestral sequences where TK activity emerged. The kinases of interest were the mitogen-activated protein kinase kinases (MAP2Ks), which exhibits tyrosine, serine, and threonine phosphorylation activities. MAP3K, a kinase with serine and threonine kinase activity, but not TK activity was used as the outgroup. This outgroup allowed for the reconstruction of an ancestral sequence without TK activity and comparison to the ancestral sequence with TK activity to determine which substitutions were responsible for the emergence of TK activity. Sequences of kinase domains were collected using the National Center for Biotechnology Information's BLAST tool and phylogenetics software was used to construct the phylogenetic tree. By identifying and comparing the substitutions responsible for TK activity in MAP2Ks to other instances of TK activity, this study provides insight into the reproducibility of the evolutionary process that led to TK activity and sheds light on evolutionary processes more broadly. Keywords: Phylogenetics; Evolution; Reconstruction; Kinase; Chance and Contingency

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Purdue University / 2024

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Rachel Marie Isaac

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