The hard clam genome reveals massive expansion and diversification of inhibitors of apoptosis in Bivalvia

Hao Song, Ximing Guo, Lina Sun, Qianghui Wang, Fengming Han, Haiyan Wang, Gregory A. Wray, Phillip Davidson, Qing Wang, Zhi Hu, Cong Zhou, Zhenglin Yu, Meijie Yang, Jie Feng, Pu Shi, Yi Zhou, Libin Zhang, Tao Zhang

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Background: Inhibitors of apoptosis (IAPs) are critical regulators of programmed cell death that are essential for development, oncogenesis, and immune and stress responses. However, available knowledge regarding IAP is largely biased toward humans and model species, while the distribution, function, and evolutionary novelties of this gene family remain poorly understood in many taxa, including Mollusca, the second most speciose phylum of Metazoa. Results: Here, we present a chromosome-level genome assembly of an economically significant bivalve, the hard clam Mercenaria mercenaria, which reveals an unexpected and dramatic expansion of the IAP gene family to 159 members, the largest IAP gene repertoire observed in any metazoan. Comparative genome analysis reveals that this massive expansion is characteristic of bivalves more generally. Reconstruction of the evolutionary history of molluscan IAP genes indicates that most originated in early metazoans and greatly expanded in Bivalvia through both lineage-specific tandem duplication and retroposition, with 37.1% of hard clam IAPs located on a single chromosome. The expanded IAPs have been subjected to frequent domain shuffling, which has in turn shaped their architectural diversity. Further, we observed that extant IAPs exhibit dynamic and orchestrated expression patterns among tissues and in response to different environmental stressors. Conclusions: Our results suggest that sophisticated regulation of apoptosis enabled by the massive expansion and diversification of IAPs has been crucial for the evolutionary success of hard clam and other molluscan lineages, allowing them to cope with local environmental stresses. This study broadens our understanding of IAP proteins and expression diversity and provides novel resources for studying molluscan biology and IAP function and evolution.

Original languageEnglish (US)
Article number15
JournalBMC Biology
Issue number1
StatePublished - Dec 2021

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Structural Biology
  • Ecology, Evolution, Behavior and Systematics
  • Physiology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Plant Science
  • Developmental Biology
  • Cell Biology


  • Divergence
  • Gene duplication
  • IAP gene family
  • Molecular evolution
  • Mollusca


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