Evolutionary functional elaboration of the Elovl2/5 gene family in chordates

Abstract

The biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFA) provides an intriguing example on how multi-enzymatic cascades evolve. Essential LC-PUFA, such as arachidonic, eicosapentaenoic, and docosahexaenoic acids (DHA), can be acquired from the diet but are also endogenously retailored from C precursors through consecutive elongations and desaturations catalyzed, respectively, by fatty acyl elongase and desaturase enzymes. The molecular wiring of this enzymatic pathway defines the ability of a species to biosynthesize LC-PUFA. Exactly when and how in animal evolution a functional LC-PUFA pathway emerged is still elusive. Here we examine key components of the LC-PUFA cascade, the Elovl2/Elovl5 elongases, from amphioxus, an invertebrate chordate, the sea lamprey, a representative of agnathans, and the elephant shark, a basal jawed vertebrate. We show that Elovl2 and Elovl5 emerged from genome duplications in vertebrate ancestry. The single Elovl2/5 from amphioxus efficiently elongates C and C and, to a marked lesser extent, C LC-PUFA. Lamprey is incapable of elongating C substrates. The elephant shark Elovl2 showed that the ability to efficiently elongate C PUFA and thus to synthesize DHA through the Sprecher pathway, emerged in the jawed vertebrate ancestor. Our findings illustrate how non-integrated >metabolic islands> evolve into fully wired pathways upon duplication and neofunctionalization.