Table 1.
Numbers of Retn and Retnl genes found in groups of vertebrate species.
Fig 1.
Alignment of Retn and Retnl protein sequences.
Alignment of predicted resistin and resistin-like protein sequences from human, mouse, opossum, Anole lizard, and coelacanth (lobe-finned fish). The human Retn sequence is shown at the top in single letter code. Dots in the alignments represent identity to the human Retn sequence, with differences indicated in single letter code. Asterisks below the alignment identify residues that are perfectly conserved among all of the selected sequences.
Fig 2.
Phylogeny of Retn and Retnl genes.
Phylogeny inferred by the Bayesian method for 136 Retn and Retnl sequences from diverse vertebrates. The phylogeny was rooted with the Coelacanth Retn sequence. Similar phylogenies were obtained if sequences from Sauria (coelacanth sequence not used) were used as the outgroup or if other methods were used (e.g., see S6 Fig). Numbers at the nodes indicate posterior probabilities, with those for the nodes in early mammalian evolution shown in bold. Branch lengths are proportional to the inferred amount of change, with the scale bar at the bottom. Diamonds indicate inferred gene duplication events. Retnl genes are shown in the upper part of the tree while Retn genes are below.
Fig 3.
Genomic organization of genes near Retn genes of representative vertebrate species.
Retn genes are labeled in red. Genes that share genomic location with human genes are labeled in yellow, while genes labeled in green are either lineage-specific genes or are found at a different genomic location in the human genome (genes without name do not have a human ortholog). The painted turtle genomic neighborhood is composed of two scaffolds that are likely adjacent. Chromosome, genomic scaffold, or sequence accession numbers, with approximate coordinates and size, of the displayed fragment are shown. See S1 Table for details on genomic locations of Retn genes. Gene sizes and distances between genes are not to scale. Arrowheads indicate direction of transcription. Gene symbols are: Retn, resistin; Xab2, XPA binding protein 2; Pet100, PET100 homolog; Pcp2, Purkinje cell protein 2; Stxbp2, Syntaxin binding protein 2; Mcemp1, Mast cell-expressed membrane protein 1; Trappc5, Trafficking protein particle complex 5; Fcer2, Fc fragment of IgE, low affinity II, receptor for (CD23); Clec4g, C-type lectin domain family 4, member G; Kiss1r, KISS1 receptor; Jrk, Jerky; Pglyrp6, Peptidoglycan recognition protein 6; Rasal3, RAS protein activator like 3; Emr-like, Egf-like module containing, mucin-like, hormone receptor-like; Wiz, Widely interspaced zinc finger motifs; and Fam102b, Family with sequence similarity 102, member B.
Fig 4.
Genomic organization of genes near Retnl genes of representative vertebrate species.
Retnl genes are labeled in red. Genes that share genomic location with human genes are labeled in black, while genes labeled in green are either lineage-specific genes or are found at a different genomic location in the human genome (genes without names do not have a human ortholog). Chromosome, genomic scaffold, or sequence accession numbers, with approximate coordinates and size, of the displayed fragment is shown. See S1 Table for details on genomic locations of Retnl genes. Gene sizes and distances between genes are not to scale. Arrowheads indicate direction of transcription. Gene symbols are: Retnl, resistin-like; Morc1, MORC family CW-type zinc finger 1; Guca1c, Guanylate cyclase activator 1C; Trat1, T cell receptor associated transmembrane adaptor 1; Dzip3, DAZ interacting zinc finger protein 3; Kiaa1524, KIAA1524; Myh15, Myosin, heavy chain 15; Hhla2, HERV-H LTR-associating 2; Hjurp, Holliday junction recognition protein; Sh2d1b, SH2 domain containing 1B; Ift57, Intraflagellar transport 57; and Mrps23, Mitochondrial ribosomal protein S23.
Fig 5.
Model for the evolution of the resistin and resistin-like genes.
Retn and Retnl genes are indicated by the red arrows, with the arrow pointing in the direction of transcription. Other genes are shown in yellow (locus of origin) or blue (location of inserted Retnl gene). Curved arrows indicated gene duplications that were either a transposition (to generate Retnl) or tandem, on the rodent and primate lineages. X’s indicate inactivating mutations in the primate and artiodactyl genes that generate pseudogenes. (A). In the ancestor to mammals, Retn was located in the locus of origin. (B). On an early mammalian lineage, prior to the placental mammal-marsupial divergence, a copy of Retn was transposed to a new genomic location to generate the Retnl gene. The transposition likely allowed Retnl to acquire a novel expression pattern. (C). Retn and Retnl genes have different fates on divergent mammalian lineages. While Retn remained as a single copy intact gene on different mammalian lineages, Retnl had different fates, raising the possibility that it acquired lineage-specific functions. Retnl remained as a single copy gene in perissodactyls, duplicated intact (potentially functional) copies in rodents, duplicated and generated a pseudogene in primates, or was inactivated in artiodactyls.