Cover image of Systematic Biology ( March 2010 )

—Horizontal gene transfer (HGT) is one of the main mechanisms driving the evolution of microorganisms. Its accurate identification is one of the major challenges posed by reticulate evolution. In this article, we describe a new polynomial-time algorithm for inferring HGT events and compare 3 existing and 1 new tree comparison indices in the context of HGT identification. The proposed algorithm can rely on different optimization criteria, including least squares (LS), Robinson and Foulds (RF) distance, quartet distance (QD), and bipartition dissimilarity (BD), when searching for an optimal scenario of subtree prune and regraft (SPR) moves needed to transform the given species tree into the given gene tree. As the simulation results suggest, the algorithmic strategy based on BD, introduced in this article, generally provides better results than those based on LS, RF, and QD. The BD-based algorithm also proved to be more accurate and faster than a well-known polynomial time heuristic RIATA-HGT. Moreover, the HGT recovery results yielded by BD were generally equivalent to those provided by the exponential-time algorithm LatTrans, but a clear gain in running time was obtained using the new algorithm. Finally, a statistical framework for assessing the reliability of obtained HGTs by bootstrap analysis is also presented. [Bipartition dissimilarity; bootstrap analysis; horizontal gene transfer; least squares; phylogenetic tree; quartet distance; Robinson and Foulds topological distance. ] The understanding that horizontal gene transfer (HGT, also called lateral gene transfer) might have played a key role in species evolution is one of the most fundamental changes in our perception of general aspects of molecular biology (Doolittle et al. 2003; Koonin 2003). HGT is a direct transfer of genetic material from one lineage to another. Bacteria and archaea have sophisticated mechanisms for the acquisition of new genes through HGT, which may have been favored by natural selection as a more rapid way of adaptation than the alteration of gene functions through numerous point mutations (Doolittle 1999; Gogarten et al. 2002; Zhaxybayeva et al. 2004). The 3 main types of HGT are the following: transformation, consisting of uptake of naked DNA from the environment, conjugation that is mediated by conjugal plasmids or transposons, and transduction, consisting of DNA transfer by phage. There are 2 main approaches to identify the genes that have been transferred horizontally. First, sequence analysis of the host genome may reveal areas with GC content or codon usage patterns atypical for it (Lawrence and Ochman 1997). Assuming that these sequences have not arisen from a selective process means that they might have been acquired horizontally. Tsirigos and Rigoutsos (2005) discussed a method for detecting HGT that relies on a gene’s nucleotide composition and obviates the need for knowledge of codon boundaries. Second, the comparison of a morphology-based species tree or molecular tree based on a molecule that is assumed to be refractory to HGT (e.g., 16S rRNA or 23S rRNA) against a phylogeny of an observed gene, inferred for the same set of organisms, may reveal topological conflicts that can be explained by HGT. Ribosomal genes may also undergo HGT, but they seem to do it at a relatively low rate, and can serve as a first approximation to a species (i.e., organismal) phylogeny in the absence of other data (Acinas et al. 2004). The latter approach includes numerous methods that started to appear in the early 1990s. First methods using network-based models to recover HGT were proposed by Hein (1990), von Haeseler and Churchill (1993), Page (1994), and Page and Charleston (1998). Mirkin et al. (1995) put forward a tree reconciliation method that combines different gene trees into a unique organismal phylogeny. The paper by Moret et al. (2004) presents an overview of the network modeling in phylogenetics. Maddison (1997) and Page and Charleston (1998) first described the set of evolutionary rules that should be taken into account when modeling HGT. Several recently proposed methods deal with approximation of the subtree prune and regraft (SPR) distance that is closely related to the inference of HGT events. Bordewich and Semple (2004) showed that computing the SPR distance between rooted binary trees is NPhard. A HGT model allowing for mapping numerous gene trees into a species tree was described by Hallett and Lagergren (2001; LatTrans algorithm). The LatTrans algorithm generates all shortest SPR scenarios but is exponential in the number of transfers. On the other hand, Boc and Makarenkov (2003) proposed an algorithm that can be suitable for inferring partial HGTs. Mirkin et al. (2003) designed an algorithm for the reconciliation of phyletic patterns with a species tree by postulating gene loss, gene emergence, and HGT. The latter authors showed that in each situation, their algorithm provides a parsimonious evolutionary scenario consisting of mapping gene loss and gain events into a species phylogenetic tree. Hallett et al. (2004) introduced