有关扇贝的最前沿研究在这里！（原创 海生张）

2017年4月3日，中国海洋大学海洋生命学院包振民教授的研究团队在Nature子刊Nature Ecology & Evolution上发表题为“Scallop genome provides insights into evolution of bilaterian karyotype and development”的研究文章。2017年11月23日，包老师团队又在Nature子刊Nature Communication上发文，题为“Scallop genome reveals molecular adaptations tosemi-sessile life and neurotoxins” 。 把小扇贝研究到这种高度、一年发两篇Nature子刊，可以说很大佬了！

我深居此实验室数月，仔细研读文献，深入接触文献的作者们，找到了这两篇Nature子刊背后的故事。你确定不看看？

1.我可能并不是真的认识扇贝

2

——“扇贝”？不就是“清蒸扇贝”和“蒜蓉扇贝”或者“辣炒扇贝肉”的那个扇贝嘛？！

——对呀！你还知道扇贝的什么知识呢？

——扇贝属于软体动物门瓣鳃纲异形亚纲珍珠贝目扇贝科。我国是扇贝的主产国之一，沿海经济扇贝种类主要有4种，分别是栉孔扇贝（Chlamys farreri）、海湾扇贝（Argopecten irradians）、虾夷扇贝（Patinopecten yessoensis）和华贵栉孔扇贝（Chlamys nobilis）。其中，虾夷扇贝和海湾扇贝由国外引进。

——那你知道的真不少。

（啪！我就甩过来两张图）

常见扇贝（图片来自海大海洋生物遗传学与育种教育部重点实验室）

栉孔扇贝内部结构（© 海生张）

栉孔扇贝就是咱们常见、常吃的扇贝啦，清蒸、蒜蓉…… 栉孔扇贝目前已成为我国海水养殖主要优势品种之一，在辽宁、河北和山东，尤其是山东沿海已形成相当大的养殖规模。在青岛的海鲜市场上很常见。11月这篇发表于Nature Communication上的文章Scallop genome reveals molecular adaptations tosemi-sessile life and neurotoxins研究的就是栉孔扇贝啦。

而虾夷扇贝原产于日本、俄罗斯千岛群岛南部等水域，1982年引入我国山东和辽宁，目前养殖分布在黄渤海，15℃为其最适生长温度。4月这篇发表于Nature Ecology & Evolution上的文章Scallop genome provides insights into evolution of bilaterian karyotype and development讲的就是虾夷扇贝的故事。

虾夷扇贝哪里买？青岛台东海鲜市场早市有一家卖，新鲜的34元/斤，不太新鲜的也得30。（笔者连着两天探访过清晨五点半的青岛台东一路海鲜市场）

2.谁说研究扇贝的就只能讲扇贝的故事？

——通过扇贝来看生物的宏观进化

(1)扇贝的基因组是“化石基因组”？

作者们发现扇贝保留了近乎完美的古老染色体核型，是迄今为止发现的最接近双侧对称动物祖先的染色体核型。扇贝（单倍体染色体数为19）核型较为完美地与科学家们预言的双侧对称动物祖先（单倍体染色体数17）核型（Simakov, O. et al. Insights into bilaterian evolution from three spiralian genomes. Nature 493, 526–531 (2013)）相符合。而这个“化石基因组”对于研究双侧对称生物演化有着重要的意义。扇贝基因组，一把通向未知世界的神奇的钥匙 。

The outstanding preservation of ancestral bilateriankaryotype in the scallop genome. Chromosome-based macrosynteny is shown in theform of dot plots with comparisons between the chromosomes of 12 bilateriangenomes (x axis) and the 17 presumed bilaterian ALGs (ALG1–17, y axis)that were previously reconstructed5.The scallop genome anchored in 19 chromosomes shows the highest level ofchromosome preservation (conservation index (CI) = 0.81) that far exceeds those of other bilaterians (CI = 0–0.42) withchromosome-level assemblies, suggesting that the scallop has a karyotypeclosely resembling that of a bilaterian ancestor. The haploid chromosome number(n) is shown for each species, and the CI measures the extent ofpreservation of bilaterian ALGs in each species. The chromosome-anchored genomeassemblies of Pacific oyster (C. gigas) and pearl oyster (P. fucata)were generated in this study by using two recently published high-densitylinkage maps

（2）Hox表达调控的新模式？

作者们发现扇贝基因组保留了最完整的Hox和ParaHox基因簇，提出了双侧对称动物Hox基因簇分段共线性（STC）表达新模式，阐明了动物体制发生决定基因Hox基因簇表达的起源和演化途径。

a, Chromosomal organization of Hox and ParaHox genesof scallop and other lophotrochozoans. Unlike other lophotrochozoans whose Hoxand ParaHox clusters are usually fragmented, both clusters arepresent as single, intact clusters in scallop, possibly representing theancestral state of these clusters in the lophotrochozoan ancestor (top).Horizontal arrows and triangles denote transcription orientation and externalgene insertion, respectively.

c, Temporal expression of scallop Hox and ParaHox clustergenes. Expression of ParaHox cluster follows temporal co-linearityduring embryonic and larval stages, whereas expression of Hox clusterexhibits an STC for four subclusters (S1: Hox1–Hox3, S2: Hox4–Hox5,S3: Lox5–Lox2, S4: Post2–Post1), with leading genesgenerally activated earlier than their followers in each subcluster. Verticalthick arrows indicate co-activation of leading genes of four subclusters,whereas thin arrows indicate gene activation order within each subcluster orthe whole cluster. 2-8cell, 2–8 cells; Bla, blastula; Gas, gastrula; Tro,trochophore; Dst, D-stage larva; Ped, pediveliger; Juv, juvenile.

d, Spatially co-linear expression of four leading genes (Hox1,Hox4, Lox5, Post2) of each subcluster at the gastrulastage. The expression regions of four leading genes almost span the entireanterior–posterior body axis, suggesting the prominent roles of these leadinggenes in early body plan determination. Expression of other Hox genes isnot detectable at this stage (see Supplementary Fig. 23) except Lox4,which is less likely to be a candidate leading gene as its expression does notconform to the characteristic pattern of leading genes (stronger expression atearly developmental stages than latter stages). A, anterior; P, posterior; V,ventral; D, dorsal. Scale bar, 50 μm.

Schematic illustration ofvarious types of Hox temporal expression andtheir possible evolutionary origins. The phenomenon of STC exists in an intact Hoxcluster of scallop and fragmented clusters of different lophotrochozoanlineages (bivalves and annelids)9,29 anddistantly related bilaterian groups (ecdysozoan and deuterostome)30,31, suggesting that STC could be ancestral. Thebasal bilaterian acoels33 have only threeunlinked Hox genes (corresponding to Hox1, Hox4/5 and Postparalogous group46), and it has beenproposed that these acoel Hox genes may belong to the ancient Hox clusterof Urbilateria or proto-Urbilateria, duplication of which gives rise to presentprotostome/deuterostome Hox clusters46.In the acoel Convolutriloba longifissura, all three Hox genesshow contemporaneous expression after gastrulation32,which is consistent with the co-activation of subclusters in scallop and otherbilaterians, and suggests STC might be established along with the stepwiseduplication of primordial Hox genes. Interestingly, the Hox expressionof the annelid C. teleta exhibits an unusual mode of WTC that issubcluster-based35 (called S-WTC here),probably representing an intermediate state in evolutionary transition betweenSTC and WTC. STC may be central to the bilaterian body plan evolution and, ifindeed ancestral, would provide bilaterian ancestors great potential ingenerating diverse body plans.

3.做扇贝，还是要探究一些扇贝的生物学问题的

——看看扇贝的微观进化

3

（1）扇贝眼睛的遗传调控及进化起源

Summary of opsins and Pax genes used in cephalic andnoncephalic bilaterian eyes or light sensors from this and previous studies.The observation of cephalic and noncephalic bilaterian eyes controlled by different Pax regulators (Pax6 for the former and Pax2/5/8 for the latter) across majorbilaterian clades, supporting their different evolutionary origins.

研究发现扇贝眼睛的发生是由Pax2/5/8主导，向之前普遍认为眼睛起源单源论(以Pax6基因主导)提出了挑战。头眼（人类、果蝇等）由Pax6主导，而扇贝、线虫的躯干眼由Pax2/5/8主导。

Diversity of opsins andphototransduction cascades in scallop eyes.

a, Scallop has numerous noncephalic eyes scattered along mantlemargins, with two distinct retinal layers consisted of rhabdomeric and ciliaryPRCs, respectively (scale bars on the upper and lower images represent 5 cm and100 μm, respectively). Diverse opsin types (r-opsin, Go-opsin and c-opsin) are identified in the scallopgenome, with r-opsins showing the highest expression and probably playing aprominent role in scallop eye function. The finding of c-opsin expression inscallop eyes is intriguing, as c-opsin has not been identified in scallopsbefore and was once considered a vertebrate-type opsin for ciliaryphototranduction. Eye samples from three individuals were used in expressionevaluation with standard errors shown for eye and mantle groups.

b, Key components of different phototransduction cascades(mediated by r-opsin, Go-opsin and c-opsin)identified in the scallop genome with their gene expression in eyes relative tomantle colour-coded. The coexistence of multiple phototransduction cascades inscallop eyes is unusual and intriguing, as these cascades have been selectivelypreserved for visual function in invertebrates (r-opsin) and vertebrates(c-opsin). FC, fold change.

上图示研究发现的扇贝眼睛的多套光传导通路（分别由r-opsin、Go-opsin和c-opsin主导）及视蛋白进化分析。

（2）贝类毒素积累及耐受机制

Toxinresistance and response regulatory networks in the scallop kidney andhepatopancreas.

a Aminoacids conferring PST or TTX resistance on sodium channel Nav1 (highlighted inred) identified inthis and other studies. Skull signs indicate toxin-producing and -resistantspecies.

b Expressionof sodium channels Nav1 and Nav2, and PST concentration and toxicity levels inmajor organs of C. farreri. Toxicity (μgSTX eq. per 100 g) was determined by converting total concentration of PSTs tomicrograms of STX equivalents per 100 g of tissue.

c Temporalvariations in abundance of different PSTs and gene networks in the kidney andhepatopancreas after exposure to the toxic alga Alexandrium minutum. Toxin response modules were identified by enrichment analysis of DEGs duringexposure to A. minutum and eachmodule was annotated with the two most significantly enriched GO term(s). The green moduleis the largest kidney-specificresponse module, where cytosolic sulfotransferase (Sult) genes are enriched andhighly expressed on day 5 after A. minutum exposure (as indicated in the heatmap).

d Aschematic diagram showing different roles of the scallop hepatopancreas andkidney in toxin metabolism, with the hepatopancreas primarily responsible forPST accumulation, whereas the kidney primarily for PST transformation mediatedby SULTs.

作者们探究了扇贝对麻痹性贝毒（PST）积累、转化及耐受的组学基础，确定肾脏是扇贝毒素转化的主要器官，解析了PST攻毒过程中扇贝的基因网络调控及表达模式，提出了扇贝贝毒耐受及转化的遗传机制。

所以以后吃扇贝的时候，请先把毒素含量最高的肝胰腺（黑色一坨）和肾脏（两颗小黄豆状）剔除再吃吧！

（3）扇贝足丝组成及黏附机制

The evolution of opsin diversity and photoreceptiontuning in C. farreri.

a. Morphology of scallop eyes scattered along the edge ofmantles (left, scale bar: 1 cm), schematic structure of a typical scallop eye(middle), and expression of diverse opsin genes in scallop eyes (right). Eyesamples from three individuals were used in expression evaluation with standarderror shown for eye and mantle groups. The asterisks indicate genes showingsignificantly higher expression in eyes than in the mantle (p-value< 0.05, the exact test by edgeR).

b. R-opsin gene structures of Mollusca and Branchiopoda.Exons rather than introns were plotted in proportion, with scale barrepresenting 500 bp. NETR (neurotrypsin) and FPV246 (putative ankyrin repeatprotein) are the conserved neighboring genes.

c. Sequence similarity and Ka/Ks values of all opsingenes between the scallops of C. farreri (CF)and P. yessoensis (PY). These datawere calculated based on full protein sequences. The black line insides the boxindicates the median value, and the whiskers extend from the first or third quartiles to the minimum or maximum values.

d. Bivalve opsin phylogeny and variation at keyfunctional sites sensitive to various light ranges. Species abbreviations: Chlamys farreri (CF), Pinctada fucata (PF), Crassostrea gigas (CG), Argopecten irradians (AI), Patinopecten caurinus (PC) and Argopecten purpuratus (AP). Sitecombinations of “SFA” “GFA” and “AFA” above the major branches are the putativeancestral bivalve types deduced from extant species. Colors of the sitescorrespond to the colors or wavelengths of opsin sensitivity in human opsins

研究查明了扇贝足丝显微结构及蛋白关键组分，确定了酪氨酸酶、磷酸化酶等酶类参与的催化反应对足丝粘附起重要作用。海洋生物黏附材料？听起来就很有应用前景呢！

4.文章背后的故事？我们学到了什么样的科研精神？

4

4

合作。这两篇文章都不是以一人之力、一实验室之力完成。攻克一个科学难题，可能需要来自不同学校/科研机构、不同研究方向的科研工作者们的群策群力。

自信。“我一个做水产育种的为啥不能发表最顶级的文章？！” 这种自信不是盲目自大，而是在实验室老师们经历多次失败后成长
起来的。

努力。看起来是包老师团队在一年内发表了这两篇文章，可是这两篇文章的工作花了整个科研团队好几年的时间，可谓厚积薄发！

向研究人员们致敬！

此外，海生张最近正在烟台市某育苗场从事扇贝育种工作，请看他从生产一线发来的照片。

这么大的虾夷扇贝我可是第一次见

美丽的海湾扇贝

扇贝销魂的泳姿

后续会推出《小师弟下场日记》，我们一起走进扇贝育种场，去看看我们餐桌上营养而美味的扇贝是怎么长大的。敬请期待!

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