ssu-align is an HMM-based MSA tool for ribosome's small subunit (SSU) sequences. It's bundled with three SSU models:
Approach Given a set of archaeal and bacterial sequences the tool will first identify the best model for each sequence and produce two separate alignments for archaea and bacteria, and the tool provides no merging functionality.
Rationale The underlying issue with SSU is the secondary structure, which results in: 1) indels; 2) pairwise point mutations (to maintain the secondary structure)
Problem While you can force it to use a single model for all sequences, aligning archaeal sequences to the bacterial model will produce poor results.
Solution? Nevertheless, the authors of GreenGenes claim that they've used ssu-align to produce two MSAs (one for archaea and bacteria) and build a joint phylogenetic tree using FastTree, but they say nothing about the way they've managed to merge the alignments. Am I missing some functionality from SSU-align?
Note Merging two giant MSAs using conventional tools, such as MAFFT, won't get me far.
I've already tried contacting the authors of the GreenGenes paper, but the corresponding author hasn't responded.