PT - JOURNAL ARTICLE AU - Gavryushkin, Alex AU - Whidden, Chris AU - Matsen, Frederick A TI - The combinatorics of discrete time-trees: theory and open problems AID - 10.1101/063362 DP - 2017 Jan 01 TA - bioRxiv PG - 063362 4099 - http://biorxiv.org/content/early/2017/07/17/063362.short 4100 - http://biorxiv.org/content/early/2017/07/17/063362.full AB - A time-tree is a rooted phylogenetic tree such that all internal nodes are equipped with absolute divergence dates and all leaf nodes are equipped with sampling dates. Such time-trees have become a central object of study in phylogenetics but little is known about the parameter space of such objects. Here we introduce and study a hierarchy of discrete approximations of the space of time-trees from the graph-theoretic and algorithmic point of view. One of the basic and widely used phylogenetic graphs, the NNI graph, is the roughest approximation and bottom level of our hierarchy. More refined approximations discretize the relative timing of evolutionary divergence and sampling dates. We study basic graph-theoretic questions for these graphs, including the size of neighborhoods, diameter upper and lower bounds, and the problem of finding shortest paths. We settle many of these questions by extending the concept of graph grammars introduced by Sleator, Tarjan, and Thurston to our graphs. Although time values greatly increase the number of possible trees, we show that 1-neighborhood sizes remain linear, allowing for efficient local exploration and construction of these graphs. We also obtain upper bounds on the r-neighborhood sizes of these graphs, including a smaller bound than was previously known for NNI.Our results open up a number of possible directions for theoretical investigation of graph-theoretic and algorithmic properties of the time-tree graphs. We discuss the directions that are most valuable for phylogenetic applications and give a list of prominent open problems for those applications. In particular, we conjecture that the split theorem applies to shortest paths in time-tree graphs, a property not shared in the general NNI case.