Hemoglobin wonders: a fascinating gas transporter dive into molluscs

Hemoglobin (Hb) has been identified in at least 14 molluscan taxa so far. Research spanning over 130 years on molluscan Hbs focuses on their genes, protein structures, functions, and evolution. Molluscan Hbs are categorized into single-, two-, and multiple-domain chains, including red blood cell, gill, and extracellular Hbs, based on the number of globin domains and their respective locations. These Hbs exhibit variation in assembly, ranging from monomeric and dimeric to higher-order multimeric forms. Typically, molluscan Hbs display moderately high oxygen affinity, weak cooperativity, and varying pH sensitivity. Hb’s potential role in antimicrobial pathways could augment the immune defense of bivalves, which may be a complement to their lack of adaptive immunity. The role of Hb as a respiratory protein in bivalves likely originated from the substitution of hemocyanin. Molluscan Hbs demonstrate adaptive evolution in response to environmental changes via various strategies (e.g. increasing Hb types, multimerization, and amino acid residue substitutions at key sites), enhancing or altering functional properties for habitat adaptation. Concurrently, an increase in Hb assembly diversity, coupled with a downward trend in oxygen affinity, is observed during molluscan differentiation and evolution. Hb in Protobranchia, Heteroconchia, and Pteriomorphia bivalves originated from separate ancestors, with Protobranchia inheriting a relative ancient molluscan Hb gene. In bivalves, extracellular Hbs share a common origin, while gill Hbs likely emerged from convergent evolution. In summary, research on molluscan Hbs offers valuable insights into the origins, biological variations, and adaptive evolution of animal Hbs.截至目前，血红蛋白（Hemoglobin, Hb）已在至少14个软体动物类群中得到鉴定。历时130余年的软体动物血红蛋白研究围绕其基因、蛋白质结构、功能与演化展开。根据珠蛋白结构域的数量及其所在位置，软体动物血红蛋白可分为单结构域、双结构域与多结构域链亚型，涵盖红细胞血红蛋白、鳃血红蛋白与细胞外血红蛋白。这类血红蛋白的组装形式存在差异，可从单体、二聚体直至高阶多聚体形式。通常而言，软体动物血红蛋白展现出中等偏高的氧亲和力、较弱的协同性以及各不相同的pH敏感性。血红蛋白在抗菌通路中的潜在作用可增强双壳类的免疫防御能力，这或许可以弥补其缺乏适应性免疫的缺陷。血红蛋白作为双壳类的呼吸蛋白，其功能可能起源于对血蓝蛋白的替代。软体动物血红蛋白可通过多种策略响应环境变化以发生适应性演化，例如增加血红蛋白亚型、发生多聚化以及关键位点的氨基酸残基替换，以此增强或改变功能特性以适应栖息环境。与此同时，在软体动物分化与演化过程中，其血红蛋白组装多样性有所提升，同时氧亲和力呈现下降趋势。原鳃亚纲、异齿亚纲与翼形亚纲双壳类的血红蛋白起源于不同的祖先类群，其中原鳃亚纲继承了相对古老的软体动物血红蛋白基因。在双壳类中，细胞外血红蛋白拥有共同的起源，而鳃血红蛋白则可能通过趋同演化产生。总而言之，针对软体动物血红蛋白的研究为动物血红蛋白的起源、生物学变异与适应性演化提供了宝贵的研究视角。