Recent studies on the evolution of mammalian flight using high-throughput sequencing technology
Bats are the only mammals capable of self-powered flight using wings.Critical adaptations for their flight include a pair of dramatically elongated hands (forelimb digits Ⅱ-Ⅴ) with broad wing membranes.Although it has been studied for over ten years,the molecular mechanism of bat wing evolution was still uncertain before 2014.Here we reviewed recently significant studies on this topic,which made a great progress on the knowledge of bat wing formation.Thousands of differentially expressed genes and regulatory elements associated with limb development were found by using advanced high-throughput sequencing technology,including whole genome sequencing,RNA-seq and ChIP-seq.Screening out from RNA-seq data,we identified seven key genes that displayed unique expression patterns in embryonic bat wings and feet,compared with mouse fore-and hindlimbs.The expression of all 5'HoxD genes (Hoxd9-13) and Tbx3,six known crucial transcription factors for limb and digit development,was extremely high and prolonged in the elongating wing area.The expression of Brinp3 (also called Fam5c),a tumor suppressor,in bat limbs was bat-specific and significantly high in all short digit regions (the thumb and foot digits).Using RNA-seq analysis,Eckalbar et al.found that more than 7000 genes and a few long noncoding RNAs,including Tbx5-asl and Hottip,were differentially expressed between forelimb and hindlimb in different stages of bat embryos.They also identified thousands of regions that were differentially modified in forelimb and hindlimb by using ChIP-seq analysis and 2796 bat-accelerated regions (BARs) within H3K27ac peaks by using comparative genomics,several of which cluster near limb-associated genes.Booker et al.discovered 166 BARs that overlap H3K27ac and p300 ChIP-seq peaks in mouse embryonic limbs.They further performed a mouse enhancer assay and showed that five Myotis lucifugus BARs drove gene expression in the embryonic mouse limb,with the majority showing differential enhancer activities compared to the mouse orthologous BAR sequences.Specially,one of them (BAR116),which was located telomeric to the HoxD cluster,had robust forelimb expression for the M.lucifugus sequence and no activity for the mouse sequence at the embryonic corresponding stage.Developing limb expression analysis of Hoxd10-13 in another species of bats (Miniopterus natalensis) showed that a high-forelimb and weak-hindlimb expression for Hoxdl0-11,which was similar to the expression trend observed for M.lucifugus BAR116 in mice.All the above results suggest that multiple changes in gene expression patterns and adaptive evolution of gene expression regulators occurred during the evolution of bat wings.Future studies should focus on functions of key developmental genes and bat-accelerated regulators,interactions between them,and pathways involving these genes.
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万方数据
维普
