With the increasing availability of genomic data, biologists aim to find more accurate descriptions of evolutionary histories influenced by secondary contact, where diverging lineages reconnect before diverging again. Such reticulate evolutionary events can be more accurately represented in phylogenetic networks than in phylogenetic trees. Since the root location of phylogenetic networks cannot be inferred from biological data under several evolutionary models, we consider semi-directed (phylogenetic) networks: partially directed graphs without a root in which the directed edges represent reticulate evolutionary events. By specifying a known outgroup, the rooted topology can be recovered from such networks. We introduce the algorithm Squirrel (Semi-directed Quarnet-based Inference to Reconstruct Level-1 Networks) which constructs a semi-directed level-1 network from a full set of quarnets (four-leaf semi-directed networks). Our method also includes a heuristic to construct such a quarnet set directly from sequence alignments. We demonstrate Squirrel’s performance through simulations and on real sequence data sets, the largest of which contains 29 aligned sequences close to 1.7 Mb long. The resulting networks are obtained on a standard laptop within a few minutes. Lastly, we prove that Squirrel is combinatorially consistent: given a full set of quarnets coming from a triangle-free semi-directed level-1 network, it is guaranteed to reconstruct the original network. Squirrel is implemented in Python, has an easy-to-use graphical user interface that takes sequence alignments or quarnets as input, and is freely available [...]

Semi-directed networks are partially directed graphs that model evolution where the directed edges represent reticulate evolutionary events. We present an algorithm that reconstructs binary n-leaf semi-directed level-1 networks in O(n ²) time from its quarnets (4-leaf subnetworks). Our method assumes we have direct access to all quarnets, yet uses only an asymptotically optimal number of O(nlog⁡n) quarnets. When the network is assumed to contain no triangles, our method instead relies only on four-cycle quarnets and the splits of the other quarnets. A variant of our algorithm works with quartets rather than quarnets and we show that it reconstructs most of a semi-directed level-1 network from an asymptotically optimal O(nlog⁡n) of the quartets it displays. Additionally, we provide an O(n ³) time algorithm that reconstructs the tree-of-blobs of any binary n-leaf semi-directed network with unbounded level from O(n ³) splits of its quarnets.