# Improved Duplication-Transfer-Loss Reconciliation with
###### Abstract  
Duplication-Transfer-Loss (DTL) reconciliation is a widely used computational technique for understanding gene family evolution and inferring horizontal gene transfer (transfer for short) in microbes. However, most existing models and implementations of DTL reconciliation cannot account for the effect of unsampled or extinct species lineages on the evolution of gene families, likely affecting their accuracy. Accounting for the presence and possible impact of any unsampled species lineages, including those that are extinct, is especially important for inferring and studying horizontal transfer since many genes in the species lineages represented in the reconciliation analysis are likely to have been acquired through horizontal transfer from unsampled lineages. While models of DTL reconciliation that account for transfer from unsampled lineages have already been proposed, they use a relatively simple framework for transfer from unsampled lineages and cannot explicitly infer the location on the species tree of each unsampled or extinct lineage associated with an identified transfer event. Furthermore, there does not yet exist any systematic studies to assess the impact of accounting for unsampled lineages on the accuracy of DTL reconciliation. In this work, we address these deficiencies by (i) introducing an extended DTL reconciliation model, called the _DTLx reconciliation model_, that accounts for unsampled and extinct species lineages in a new, more functional manner compared to existing models, (ii) showing that optimal reconciliations under the new DTLx reconciliation model can be computed just as efficiently as under the fastest DTL reconciliation model, (iii) providing an efficient algorithm for sampling optimal DTLx reconciliations uniformly at random, (iv) performing the first systematic simulation study to assess the impact of accounting for unsampled lineages on the accuracy of DTL reconciliation, and (v) comparing the accuracies of inferring transfers from unsampled lineages under our new model and the only other previously proposed parsimony-based model for this problem. Duplication-Transfer-Loss reconciliation; extinct and unsampled lineages; algorithms; horizontal gene transfer +
Footnote †: journal: 27 May 2021  
two by invoking gene duplication, transfer, gene loss, and speciation. Thus, the output is an embedding of the gene tree into the species tree, showing how that gene family evolved inside the species (or branches) represented in the species tree. It is common knowledge that the vast majority of species that have ever existed on Earth have gone extinct without leaving any known surviving descendants. Furthermore, only a fraction of the existing microbial species diversity of Earth has ever been described and only a small subset of this diversity is represented in genetic sequence databases. Accounting for the presence and possible impact of such unsampled species lineages is important for understanding microbial gene family evolution and studying transfer since many genes in the species lineages represented in the reconciliation analysis are likely to have been acquired through transfer from unsampled lineages, including those that have gone extinct [10]. However, most models of DTL reconciliation, such as those implemented in Mowgli [3], CoRe-PA [19], Jane [20], AnGST [5], RANGER-DTL [7,17], Notung [8], PRIME-DLTRS [14], EUCALYPT [21], eMPRess [22], etc., do not explicitly account for the potential impact of unsampled lineages on evolutionary histories of gene families. To the best of our knowledge, only two DTL reconciliation models currently exist that explicitly account for the impact of unsampled lineages: the probabilistic DTL reconciliation framework introduced by [PERSON] et al. [10] and the parsimony-based model implemented in the software cccTERA [16]. The model of [PERSON] et al. [10] was used to demonstrate that a large fraction of detectable transfers are likely acquired from unsampled lineages.