Reducing the Impact of Domain Rearrangement on Sequence Alignment and Phylogeny Reconstruction

Abstract

Existing computational approaches for studying gene family evolution generally do not account for domain rearrangement within gene families. However, it is well known that protein domain architectures often differ between genes belonging to the same gene family. In particular, domain shuffling can lead to out-of-order domains which, unless explicitly accounted for, can significantly impact even the most fundamental of tasks such as multiple sequence alignment and phylogeny inference.

In this work, we make progress towards addressing this important but often overlooked problem. Specifically, we (i) demonstrate the impact of protein domain shuffling and rearrangement on multiple sequence alignment and gene tree reconstruction accuracy, (ii) propose two new computational methods for correcting gene sequences and alignments for improved gene tree reconstruction accuracy and evaluate them using realistically simulated datasets, and (iii) assess the potential impact of our new methods and of two existing approaches, MDAT and ProDA, in practice by applying them to biological gene families. We find that the methods work very well on simulated data but that performance of all methods is mixed, and often complementary, on real biological data, with different methods helping improve different subsets of gene families.