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

Abstract

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.

Unique gene structure and paralogy define the 7D-cadherin family

“…The observed splice donor and acceptor sites match, in general, the typical consensus sequences [44]. The mouse LI-cadherin gene [45] also consists of 18 exons but is, with nearly 59 kb, six times as large (Fig. 2).…”

“…Besides the conserved structural features of both cadherins, the almost identical genomic organization is additional strong support for a common phylogenetic origin of Ksp-and LI-cadherin. We had previously shown that the intron positions within the region of the LI-cadherin gene encoding the cadherin repeats EC3 to EC7 almost perfectly match the respective regions of the classical E-, P-and N-cadherin genes encoding EC1 to EC5 [45]. The only differences are found in the second intron of EC4, which is slightly shifted and has a different phase, and in the region encoding the premembrane repeat (EC7), which contains an additional intron.…”

“…A detailed experimental and in silico analysis of the genomic neighborhood of Ksp-and LI-cadherin revealed an [45]. Taken together, the following scenario of the Ksp-/LIcadherin evolution seems very likely.…”

“…Taken together, the following scenario of the Ksp-/LIcadherin evolution seems very likely. First, an ancestral cadherin with seven cadherin repeats evolved from a fiverepeat precursor cadherin by a partial gene duplication event [45]. Second, before the divergence of land vertebrates and teleost fish, a genome or segmental chromosomal duplication involving the Ksp-/LI-cadherin ancestor gene led to the origin of an additional cadherin gene within a highly paralogous environment.…”

HNF1α and CDX2 transcriptional factors bind to cadherin‐17 (CDH17) gene promoter and modulate its expression in hepatocellular carcinoma

“…Cadherin-17 (CDH17) or liver intestine-cadherin (LI-cadherin) is a member of non-classical cadherin family [Jung et al, 2004], implicating its functional role in cell adhesion. Yet, CDH17 was initially identified as a proton-dependent peptide transporter-1 in human colon adenocarcinoma Caco-2 cells [Dantzig et al, 1994].…”