Phylogenetic inference of the emergence of sequence modules and protein-protein interactions in the ADAMTS-TSL family
Fig 3
Identification of modules by partial local multiple alignment.
We show here a schematic PLMA of sequences S1, …, S5 composed of the alignment blocks B1, …, B6. This example illustrates the locality of the alignments: each alignment of positions is supported by a local alignment of sequences, leaving possibly other sequence positions unaligned. For instance the alignment block B2 is local since it aligns only the two segments M2.3 and M2.4 of the sequences S3 and S4, and no other positions of these sequences. Local alignments authorize to align only subsets of adjacent positions from each sequence. In an orthogonal way, partial alignments authorize to align positions of only a subset of the sequences. This is also illustrated by B2 which is partial since it aligns only positions from S3 and S4 (and does not even align them to positions of the block B1 above B2). Partial local alignments are not limited to pairwise alignment: the block B3 is an example of partial local alignment block, aligning the segments M3.2, M3.3 and M3.4 from sequences S2, S3 and S4, that can be built from the pairwise local alignments (highlighted here in blue colors) of the segments M3.2 with M3.3, M3.3 with M3.4 and M3.2 with M3.4. The PLMA blocks align each a set of segments conserved specifically in a sequence subset. This set of segments, provided that they are long enough, is said to be a conserved sequence module. Let us assume here that all the blocks, except B6, align segments of 5 or more residues. The set of segments {M2.3, M2.4} aligned in B2 defines then for instance the module M2, while the block B3 enables to identify the module M3 = {M3.2, M3.3, M3.4}. Blocks B4, B5 and B6 illustrates how the definition of the blocks –requiring that each segment is aligned to, and only to, all the other segments of the block– enables to split possibly longer local alignments to identify segments specifically conserved in sequence subsets: even if the concatenation of M4.1 and M5.1 is locally aligned to the concatenation of M4.3 and M5.3 (this could be for instance a pairwise alignment used to build the PLMA), none of these two concatenations is locally aligned to M5.2. In this case, the maximal set of segments aligned with M5.2 is {M5.1, M5.3, M5.2} and the modules are here M4 = {M4.1, M4.3} specifically conserved in {S1, S3} and M5 = {M5.1, M5.3, M5.2} specifically conserved in {S1, S3, S2}. Similarly, the block B6 aligns the segments S6.3 and S6.2 but, in contrast with the segments aligned by B4, these segments are shorter than 5 residues and do not define a module.