The evolutionary history of the stearoyl-CoA desaturase gene family in vertebrates

Abstract

Background: Stearoyl-CoA desaturases (SCDs) are key enzymes involved in de novo monounsaturated fatty acid synthesis. They catalyze the desaturation of saturated fatty acyl-CoA substrates at the delta-9 position, generating essential components of phospholipids, triglycerides, cholesterol esters and wax esters. Despite being crucial for interpreting SCDs roles across species, the evolutionary history of the SCD gene family in vertebrates has yet to be elucidated, in particular their isoform diversity, origin and function. This work aims to contribute to this fundamental effort.

Results: We show here, through comparative genomics and phylogenetics that the SCD gene family underwent an unexpectedly complex history of duplication and loss events. Paralogy analysis hints that SCD1 and SCD5 genes emerged as part of the whole genome duplications (2R) that occurred at the stem of the vertebrate lineage. The SCD1 gene family expanded in rodents with the parallel loss of SCD5 in the Muridae family. The SCD1 gene expansion is also observed in the Lagomorpha although without the SCD5 loss. In the amphibian Xenopus tropicalis we find a single SCD1 gene but not SCD5, though this could be due to genome incompleteness. In the analysed teleost species no SCD5 is found, while the surrounding SCD5-less locus is conserved in comparison to tetrapods. In addition, the teleost SCD1 gene repertoire expanded to two copies as a result of the teleost specific genome duplication (3R). Finally, we describe clear orthologues of SCD1 and SCD5 in the chondrichthian, Scyliorhinus canicula, a representative of the oldest extant jawed vertebrate clade. Expression analysis in S. canicula shows that whilst SCD1 is ubiquitous, SCD5 is mainly expressed in the brain, a pattern which might indicate an evolutionary conserved function.

Conclusion: We conclude that the SCD1 and SCD5 genes emerged as part of the 2R genome duplications. We propose that the evolutionary conserved gene expression between distinct lineages underpins the importance of SCD activity in the brain (and probably the pancreas), in a yet to be defined role. We argue that an expression independent of an external stimulus, such as diet induced activity, emerged as a novel function in vertebrate ancestry allocated to the SCD5 isoform in various tissues (e.g. brain and pancreas), and it was selectively maintained throughout vertebrate evolution.

Figure 1

Stearoyl-CoA desaturase role in fatty acid desaturation. The four numbered boxes indicate the transmembrane domains.

Figure 2

(A) Chromosomal location of the SCD1 and SCD5 genes in Homo sapiens, and their neighbouring genes. Paralogues of gene families with multiple members are shown below each ORF, with distance in Mb to the p telomere of the respective chromosome. Arrows denote gene orientation. Phylogenetic analysis was performed to unveil their duplication pattern (Additional file_1) unless already available. (B) Genomic locus of Branchiostoma floridae SCD-like genes and the neighbouring gene families whose human paralogues localise to expected regions of human SCD paralogy (Hsa10, Hsa4, Hsa5 and Hsa2/8). Gene families with no clear homologues in humans, or gene families that do not localise to the NK-linked paralogon are not labelled (e.g. BfSCDc). The GenBank accession number of each B. floridae SCD scaffold is shown.

Figure 3

Maximum likelihood tree of SCD genes, with bootstrap values shown at each node. Ciona savignyi (SCDa [ENSCSAVP00000003593], SCDb [ENSCSAVP00000004039], and SCDc [ENSCSAVP00000003934]), Branchiostoma floridae (SCDa [XP_002588865], SCDb [XP_002585987], and SCDc [XP_002596094]), Scyliorhinus canicula (ScSCD1 [JF729408] and ScSCD5 [JF729409]), Anolis carolinensis (SCD1 [ENSACAP00000010645] and SCD5 [ENSACAP00000010271]), Polypterus senegalus (SCD1 [JF729410]), Salmo salar (SCD1a [NP_001133452]), Takifugu rubripes (SCD1a [ENSTRUP00000031286] and SCD1b [AAU89872]), Tetraodon nigroviridis (SCD1a [ENSTNIP00000022600] and SCD1b [ENSTNIP00000002814]), Oryzias latipes (SCD1a [ENSORLP00000011565] and SCD1b [ENSORLP00000008592]), Gasterosteus aculeatus (SCD1a [ENSGACP00000003149] and SCD1b [ENSGACP00000011262]), Oreochromis mossambicus (SCD1a [AAN77732]), Trematomus bernacchii (SCD1a [ACI16378]), O. anatinus (SCD1 [ENSOANP00000003925]), Monodelphis domestica (SCD1 [ENSMODP00000013317] and SCD5 [ENSMODP00000015016]), Loxodonta africana (SCD1 [ENSLAFP00000014914] and SCD5 [ENSLAFP00000013895]), Erinaceus europaeus (SCD1 [ENSEEUP00000005718] and SCD5 [ENSEEUP00000010623]), Pan troglodytes (SCD1 [ENSPTRP00000005002] and SCD5 [ENSPTRP00000027870]), Sus scrofa (SCD1 [ENSSSCP00000011244] and SCD5 [ENSSSCP00000009859]) Homo Sapiens (SCD1 [ENSP00000359380] and SCD5 [ENSP00000316329]), Taeniopygia guttata (SCD1 [ENSTGUP00000007924 and SCD5 [ENSTGUP00000002919), Gallus gallus (SCD1 [ENSGALP00000039331] and SCD5 [ENSGALP00000018194]), Xenopus laevis (SCD1 [AAH81254]) Xenopus tropicalis (SCD1 [ENSXETP00000051240]), Mus musculus (SCD1 [CAJ18540], SCD2 [NP_033154], SCD3 [NP_077770] and SCD4 [AAH38322]), Rattus norvegicus (SCD1 [NP_631931], SCD2 [NP_114029] and SCD4 [XP_574671]), Oryctolagus cuniculus (SCD1 [XP_002718695], SCD2 [XP_002718696], SCD3 [XP_002718697], SCD4 [XP_002718662] and SCD5 [ENSOCUP00000005142]) and Cavia porcellus (SCD2 [ENSCPOP00000008837], SCD4 [ENSCPOP00000009812] and SCD5 [ENSCPOP00000002936]).

Figure 4

SCD1 (A), SCD5 (B) gene loci in tetrapod species; SCD1a/SCD1b (C) and SCD5 (D) gene loci in teleost species. Hs - H. sapiens, Mm - M. musculus, Oc - O. cuniculus, Oa - O. anatinus, Md - M. domestica, Gg - G. gallus, Ac - A. carolinensis, Xt - X. tropicalis, Ga - G. aculeatus, Ol - O. latipes, Tr - T. rubripes, Tn - T. nigroviridis, and Dr - D. rerio Arrow head indicates gene orientation, and oblique lines denote scaffold ending. Ψ indicates pseudogene.

Figure 5

Gene expression of SCD1 and SCD5 S. canicula. B - brain, G-gill, St - stomach, I-intestine, Rg-rectal gland, L-liver, K-kidney, Sp - spleen, O-ovary, and T-testis.

Figure 6

Proposed evolutionary model of SCD genes in vertebrates.