Data from: Evolutionary suppression of erythropoiesis via the modulation of TGF-β signaling in an Antarctic icefish

The Antarctic icefish, a family (Channichthyidae) of teleosts within the perciform suborder Notothenioidei, are the only known vertebrates without oxygen-transporting haemoglobins and that are largely devoid of circulating erythrocytes. To elucidate the evo-devo mechanisms underpinning the suppressed erythropoiesis in the icefish, we conducted comparative studies on the transcriptomes and microRNAomes of the primary haematopoietic tissues between an icefish (Chionodraco hamatus) and two red-blooded notothenioids (Trematomus bernacchii and Gymnodraco acuticeps). We identified substantial remodelling of the haematopoietic programs in the icefish through which erythropoiesis is selectively suppressed. Experimental verification showed that erythropoietic suppression in the icefish may be attributable to the upregulation of TGF-β signalling, which coincides with reductions in multiple transcription factors essential for erythropoiesis and the upregulation of hundreds of microRNAs, the majority (> 80%) of which potentially target erythropoiesis regulating factors. Of the six microRNAs selected for verification, three miRNAs (miR-152, miR-1388 and miR-16b) demonstrated suppressive functions on GATA1 and ALAS2, which are two factors important for erythroid differentiation, resulting in reduced numbers of erythroids in microinjected zebra fish embryos. Codon substitution analyses of the genes of the TGF-β superfamily revealed signs of positive selection in TGF-β1 and endoglin in the lineages leading to Antarctic notothenioids. Both genes are previously known to function in erythropoietic suppression. These findings implied a general trend of erythropoietic suppression in the cold-adapted notothenioid lineages through evolutionary modulation of the multi-functional TGF-β signalling pathway. This trend is more pronounced in the haemoglobin-less icefish, which may pre-emptively hinder the otherwise defective erythroids from production.

南极冰鱼是隶属于鲈形目南极鱼亚目（Notothenioidei）的真骨鱼（teleosts）鳄冰鱼科（Channichthyidae）类群，是目前已知唯一一类缺乏携氧血红蛋白且几乎无循环红细胞的脊椎动物。为阐明冰鱼红细胞生成受抑制背后的进化发育生物学（evo-devo）机制，本研究针对一种冰鱼（哈氏冰鱼Chionodraco hamatus）与两种携红细胞的南极鱼亚目类群（伯氏须南极鱼Trematomus bernacchii、尖吻裸南极鱼Gymnodraco acuticeps）的主要造血组织的转录组与微小RNA组（microRNAomes）开展了比较分析。研究发现冰鱼的造血程序发生了显著重塑，使得红细胞生成受到选择性抑制。实验验证表明，冰鱼的红细胞生成抑制可能源于转化生长因子-β（TGF-β）信号通路的上调，该现象伴随多个红细胞生成必需转录因子的表达下调，以及数百个微小RNA的表达上调，其中超过80%的微小RNA潜在靶向调控红细胞生成的因子。在选取验证的6个微小RNA中，3个（miR-152、miR-1388与miR-16b）可对红细胞系分化关键因子GATA1与ALAS2发挥抑制作用，导致显微注射后的斑马鱼胚胎中红细胞数量减少。对转化生长因子-β超家族基因的密码子替换分析显示，在通往南极鱼亚目类群的演化支系中，TGF-β1与内皮糖蛋白（endoglin）存在正选择信号。此前已有研究表明，这两种基因均参与红细胞生成的抑制过程。本研究结果表明，通过对多功能转化生长因子-β信号通路的演化调控，适应寒冷环境的南极鱼亚目类群普遍存在红细胞生成受抑制的演化趋势；这一趋势在无血红蛋白的冰鱼中更为显著，可预先阻止原本存在缺陷的红细胞生成。