Phylogenetic origin of LI-cadherin revealed by protein and gene structure analysis

The intestine specific LI-cadherin differs in its overall structure from classical and desmosomal cadherins by the presence of seven instead of five cadherin repeats and a short cytoplasmic domain. Despite the low sequence similarity, a comparative protein structure analysis revealed that LI-cadherin may have originated from a five-repeat predecessor cadherin by a duplication of the first two aminoterminal repeats. To test this hypothesis, we cloned the murine LI-cadherin gene and compared its structure to that of other cadherins. The intron-exon organization, including the intron positions and phases, is perfectly conserved between repeats 3-7 of LI-cadherin and 1-5 of classical cadherins. Moreover, the genomic structure of the repeats 1-2 and 3-4 is identical for LI-cadherin and highly similar to that of the repeats 1-2 of classical cadherins. These findings strengthen our assumption that LI-cadherin originated from an ancestral cadherin with five domains by a partial gene duplication event.