Apolipophorin II/I, apolipoprotein B, vitellogenin, and microsomal triglyceride transfer protein genes are derived from a common ancestor.
Large lipid transfer proteins (LLTP) are nonexchangeable apolipoproteins and intracellular lipid-exchange proteins involved in the assembly, secretion, and metabolism of lipoproteins. We have identified contiguous conserved sequence motifs in alignments of insect apolipophorin II/I precursor (apoLp-II/I), human apolipoprotein B (apoB), invertebrate and vertebrate vitellogenins (VTG), and the large subunit of mammalian microsomal triglyceride transfer protein (MTP). Conserved motifs present in the N-terminal part of nonexchangeable apolipoproteins encompass almost completely the large subunit of MTP, suggesting a derivation from a common ancestral functional unit, termed large lipid transfer (LLT) module. Divergence of LLTP from a common ancestor is supported by (1) the statistical significance of the combined match scores obtained after motif-based database searches, (2) the presence of several identical amino acid residues in all LLTP sequences currently available, (3) the conservation of hydrophobic clusters in an alpha-helical domain, (4) the phylogenetic analysis of the conserved sequences related to the von Willebrand factor D (VWD) module identified in nonexchangeable apolipoproteins, and (5) the presence of four and one ancestral exon boundaries in the LLT and VWD modules, respectively. Our data indicate that the genes coding for apoLp-II/I, apoB, VTG, and the MTP large subunit are members of the same multigene superfamily. LLTP have emerged from an ancestral molecule designed to ensure a pivotal event in the intracellular and extracellular transfer of lipids and liposoluble substances.
Babin
P J
PJ
UPRESA 8080 du Centre National de la Recherche Scientifique, Biologie du Développement des Poissons, Université Paris-Sud, Bât. 447, 91405 Orsay Cedex, France.
Bogerd
J
J
Kooiman
F P
FP
Van Marrewijk
W J
WJ
Van der Horst
D J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D001053:Apolipoproteins / Q000235:genetics*; D001055:Apolipoproteins B / Q000235:genetics*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005091:Exons; D006110:Grasshoppers / Q000235:genetics; D006801:Humans; D019476:Insect Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014819:Vitellogenins / Q000235:genetics*
D001053:Apolipoproteins; D001055:Apolipoproteins B; D002352:Carrier Proteins; D019476:Insect Proteins; D012333:RNA, Messenger; D014819:Vitellogenins; C042470:apolipophorin III; C106092:microsomal triglyceride transfer protein