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Natl Sci Rev
2019 Oct 01;65:993-1003. doi: 10.1093/nsr/nwz064.
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Evolutionary transition between invertebrates and vertebrates via methylation reprogramming in embryogenesis.
Xu X
,
Li G
,
Li C
,
Zhang J
,
Wang Q
,
Simmons DK
,
Chen X
,
Wijesena N
,
Zhu W
,
Wang Z
,
Wang Z
,
Ju B
,
Ci W
,
Lu X
,
Yu D
,
Wang QF
,
Aluru N
,
Oliveri P
,
Zhang YE
,
Martindale MQ
,
Liu J
.
Abstract
Major evolutionary transitions are enigmas, and the most notable enigma is between invertebrates and vertebrates, with numerous spectacular innovations. To search for the molecular connections involved, we asked whether global epigenetic changes may offer a clue by surveying the inheritance and reprogramming of parental DNA methylation across metazoans. We focused on gametes and early embryos, where the methylomes are known to evolve divergently between fish and mammals. Here, we find that methylome reprogramming during embryogenesis occurs neither in pre-bilaterians such as cnidarians nor in protostomes such as insects, but clearly presents in deuterostomes such as echinoderms and invertebrate chordates, and then becomes more evident in vertebrates. Functional association analysis suggests that DNA methylation reprogramming is associated with development, reproduction and adaptive immunity for vertebrates, but not for invertebrates. Interestingly, the single HOX cluster of invertebrates maintains unmethylated status in all stages examined. In contrast, the multiple HOX clusters show dramatic dynamics of DNA methylation during vertebrate embryogenesis. Notably, the methylation dynamics of HOX clusters are associated with their spatiotemporal expression in mammals. Our study reveals that DNA methylation reprogramming has evolved dramatically during animal evolution, especially after the evolutionary transitions from invertebrates to vertebrates, and then to mammals.
Figure 1. Conservation and divergence of global methylation patterns in animals. (a) Evolutionary tree of animal species used in this study. (b) Global average methylation levels across different animals. Cluster under bars represents evolutionary tree of animals which is derived from the Time Tree (http://timetree.org/). (c) Genomic snapshots (IGV) displaying mosaic methylation pattern in invertebrates. ‘W’ means worker bee. ‘D’ means drone bee. ‘bla’ means blastoderm. ‘gas’ represents ‘gastrula’. Vertical line height indicates the methylation level (ML). (d) Variation of methylation levels across 6 kb upstream and downstream of transcription start sites (TSSs) in sperm (methylation levels were calculated for every 100-bp bin).
Figure 2. Evolution of methylation dynamic during early embryogenesis in animals. (a)–(d) The dynamics of the average methylation levels in sea anemone (a), honey bee (b), sea urchin (c) and sea squirt (d). (e) Graphic model of DNA methylation dynamics during zebrafish early embryogenesis from previous data. ‘MBT’ means midblastula transition. (f) Graphic model of the DNA methylation dynamics during mammalian early embryogenesis from previous data. ‘E7.5’ means mouse embryos 7.5 days after fertilization. ‘6-week’ means human embryos 6-weeks after fertilization. (g) Methylation level differences between sperm and oocytes for seven species. Tree topology is from the Time Tree (http://timetree.org/).
Figure 3. Evolution of promoter reprogramming in animals. (a) Heatmaps of differentially methylated promoters between sperm and oocytes across different species. Gene ontology (GO) enrichment of genes with differentially methylated promoters was performed. The color key from blue to pink indicates the DNA methylation levels (MLs) from low to high, respectively. (b) Genomic snapshot shows reprogramming of promoters in sea urchin and human. Red boxes highlight the promoter regions.
Figure 4. Methylation of the HOX gene clusters in different taxa. (a)–(d) Genomic snapshots representing methylation of the HOX gene clusters in sperm, oocytes and early embryos of sea anemone (a), honey bee workers and drones (b), sea urchin (c) and sea squirt (d). Oblique lines represent regions of the HOX cluster that are non-contiguous or interrupted. (e)–(g) Genomic snapshots show methylation dynamics of HOX gene clusters in zebrafish (e), mouse (f) and human (g). (h) Boxplots show the promoter methylation levels (MLs) of HOX genes between 6-week embryos and placenta in human. P value was calculated by paired Wilcoxon signed-rank test. ***P < 0.001. (i) Normalized expression levels of HOXD genes in human 6-week embryos and placenta. FPKM stands for fragments per kilobase of transcript per million mapped reads.
