Figure 1. The most parsimonious tree showing evolutionary relationships between CFTR sequences. The tree is obtained from a nucleotide sequence of 627 base pairs (bp) within CFTR exon 13 through a heuristic search of PAUP (Phylogenetic Analysis Using Parsimony; Swofford, 1998) using 1000 random addition sequences. Insertions/deletions provoked by teleostean sequences were removed because of ambiguous alignment, providing 541 positions, of which 340 are informative for parsimony. Tree length is 1249 with a consistency index of 0.60 and a retention index of 0.69. Branch length is given under ACCTRAN, and numbers at nodes are bootstrap proportions calculated from 1000 pseudoreplicates, given only when above 50%. The same tree was obtained from the neighbor-joining method (data not shown). See Table 1 for the sources of CFTR sequences.

Figure 2. Global view of CFTRR domain structure and mutational pattern in the context of 21 aligned CFTR homologs (only full-length sequences are included). The sequences are aligned by using Clustal W and checked by eye. Dashes indicate gaps that were introduced to maximize alignment. Bold letters show residues identical in all species. The top lines indicate NBD1 domain (solid line) and the R domain (dashed line) originally defined by Riordan et al. (1989). The middle lines indicate the RD1 domain (solid line) and the RD2 domain (dashed line) defined by Dulhanty and Riordan (1994). The lowest lines indicate the refined NBD1 domain (solid line) and the R domain (dashed line) defined by Chen et al. 2000, 2001). The grey shading indicates PKA consensus motifs that are phosphorylated only in vitro, and the black shading indicates those sites phosphorylated in vitro and in vivo. All of the currently identified missense mutations and single amino-acid deletions are from the Cystic Fibrosis Mutation Database. See Table 1 for the source of CFTR sequences. (See also .)