Fig. 5

Ortholog analysis of Timd2 gene. a Genome structure of Havcr2-Timd2-Havcr1 in the mouse genome (top) and genome structure of HAVCR2-HAVCR1 in the human genome (bottom). A 230-kb-long DNA fragment contained Timd2 gene only exists in the mouse genome. b Gene ortholog analysis of Havcr1, Timd2, and Timd4 in human, mouse, and rat based on protein sequence. Havcr1 genes from mouse and rat were firstly clustered with Timd2 genes instead of HAVCR1 gene in the human genome. c Expression pattern of Havcr1 and Timd2 in five tissues of human (left) and mouse (middle and right). ANOVA test: p value < 0.01. d Pair-wise alignment of exons between Havcr1 (top) and Timd2 (bottom). RLTR14-int-derived Exon1 of Timd2 did not have ortholog exon in Havcr1. e Top: Epigenome browser view of ATAC-seq and ChIP-seq signals around RLTR14-int-derived TSS of Timd2 in mouse liver. The signals of ATAC-seq, H3k27ac, and TFs binding were co-localized at Timd2 TSS region within RLTR14-int element. Bottom-left: expression pattern of Rxra in five mouse tissues. Rxra showed the highest expression in the liver. ANOVA test: p-value < 0.01. Bottom-right: predicted TF binding motifs within Timd2-TSS RLTR14-int element. f Pair-wise alignment among 128 RLTR14-int copies (overlapped to RLTR14-int-derived Timd2 TSS) against to RLTR14-int consensus sequence. Top: Gene structure of full-length consensus sequence of RLTR14-int (5317 bp). Middle: 661 bp pair-wise alignment between consensus sequence and Timd2-TSS RLTR14-int element. Six TF binding motifs were identified at the exactly same positions in both consensus sequence and Timd2-TSS RLTR14-int element. Bottom-left: 661 bp pair-wise alignment and conservation of consensus sequence (1st row), Timd2-TSS RLTR14-int element (2nd row), and 127 RLTR14-int copies. Bottom-right: occupancy of six TFBSs matched to pair-wise alignment