Figure 1. A phylogenetic analysis of Plin-family genes using EsemblCompara Gene Trees (Vilella et al., 2009; Flicek et al., 2013).
Large clades are collapsed, rayfin fish are shown in detail. Original nomenclature is that of Ensembl with new names assigned for genes of zebrafish and stickleback, along with chromosome locations, to better reflect the historical origins when taking conserved syntenies into account. Source: ENSGT00500000044795.
Figure 1—figure supplement 1. Conserved syntenies for the gene Ensembl calls plin4 in percomorph fish (stickleback gene ENSGACG00000017870), which should be renamed as plin2b.
(A, D) The region of human (Homo sapiens) chromosome 9 (Hsa9) containing PLIN2. (B) The region of stickleback linkage group 7 (Gac7) containing plin2a. (C) The region of Gac9 containing plin2b. Compara Gene Tree analysis suggested that stickleback (Gasterosteus aculeatus) has an ortholog (ENSGACG00000017870) of the human PLIN4 gene. Given the absence of a PLIN4 ortholog in non-mammalian lobefins, we examined this conclusion in more detail by performing conserved synteny analysis using the Synteny Database (Catchen et al., 2009, 2011b). Analysis showed that the chromosome segment containing ENSGACG00000017870 shares conserved syntenies with the region of Hsa9 that contains PLIN2, not the region on Hsa19 that contains PLIN4. Further analysis showed that the region of Gac9 that contains ENSGACG00000017870 shares many paralogs with the region of Gac7 that contains what Ensembl calls plin2 (ENSGACG00000019638), for example, ‘LGI(2of2) and LGI(1of2), CCDC145(2of2) and CCDC145(1of2), MYOZ2(1of2) and MYOZ2(2of2)' and others. We conclude that these two chromosome segments originated in the teleost genome duplication (TGD) event (Amores and Force, 1998; Postlethwait et al., 1999; Taylor et al., 2003; Jaillon et al., 2004a) and that the percomorph clade labeled ‘PLIN4’ by Compara Gene Tree is actually a TGD duplicate of human PLIN2. Under this interpretation, ancestral teleosts had plin2a and plin2b genes and that plin2b was lost in ostariophysans, including zebrafish and blind cavefish (Asyanax mexicanum).
Figure 1—figure supplement 2. A model for the origin of plin genes that fits available data.
Today’s bony vertebrate plin genes come from a single gene in an ancient chordate ancestor (Step 1). VGD1 (the first round of vertebrate genome duplication) produced two genes: the precursor to plin1 + plin6, and the precursor to plin2 + plin3/4/5 (Step 2). VGD2 (the second round of vertebrate genome duplication) produced four genes, plin1, plin6, plin2 and the precursor plin3/4/5 (Step 3). After VGD2, the lineage of ray fin fish, including gar and teleosts, diverged from the lineage of lobe fin fish, including coelacanth and tetrapods (Step 4), and plin6 apparently disappeared in stem lobe fins (Step 5). Before the divergence of birds and mammals, the ancestor of Plin3/4/5 duplicated to make tandem copies of Plin3 and the precursor to PLIN4/5 (Step 6). After the divergence of lineages leading to birds and mammals, the PLIN4/5 precursor duplicated in the human lineage to make tandem duplicate genes PLIN4 and PLIN5 (Step 7). Along the ray fin branch of bony vertebrates, the teleost lineage diverged from the gar lineage (Step 8) and then the TGD (teleost genome duplication) event produced copies of the four original VGD2 ohnologs, making eight plin family genes (Step 9). The ‘b’ copies of plin1, plin6, and plin3/4/5 were lost before the divergence of ostariophysans (including zebrafish) from percomorphs (including Amazon molly; Step 10). In contrast, both ‘a’ and ‘b’ copies of plin2 were retained in Amazon molly and some other percomorphs, but lost in the zebrafish lineage (Step 11).