Mucin CYS domains are ancient and highly conserved modules that evolved in concert.
BACKGROUND
Many large secreted gel-forming mucins contain multiple copies of a "naked" cysteine-enriched domain (CYS domain) that interrupt or are adjacent to mucin domains (Ser/Thr/Pro regions). There is less similarity of homologous CYS sequences between species than there is across CYS repeats within species. These CYS domains are likely implicated in reversible mucin-mucin interactions that play a central role in mucus properties.


RESULTS
The use of multiple genome sequences in a comparative analysis of CYS sequences identified new mucins containing the CYS domain in various species. Furthermore, analysis showed that this domain is at least 650 million-year old and that CYS sequences evolved under strong selective pressure in concerted fashion in all species examined by two mechanisms that never coexist within a given gene: either multiplication of exons encoding CYS modules or successive intra-exonic duplications.


CONCLUSIONS
The CYS sequences appear to have undergone concerted evolution with a high selective pressure to conserve cysteine and other amino acid residues. This domain is the best-conserved domain in secreted mucins pointing toward an important common function in many different organisms.
Desseyn
Jean-Luc
JL
EA3925, 1 place de Verdun, 59045 Lille, France. jean-luc.desseyn@inserm.fr
D000818:Animals; D017124:Conserved Sequence; D003545:Cysteine / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons; D006801:Humans; D009077:Mucins / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D054730:Protein Interaction Domains and Motifs; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D009077:Mucins; D003545:Cysteine