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

Journal Article (Journal Article)


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.


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.


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.

Full Text

Duke Authors

Cited Authors

  • Song, H; Guo, X; Sun, L; Wang, Q; Han, F; Wang, H; Wray, GA; Davidson, P; Wang, Q; Hu, Z; Zhou, C; Yu, Z; Yang, M; Feng, J; Shi, P; Zhou, Y; Zhang, L; Zhang, T

Published Date

  • January 25, 2021

Published In

Volume / Issue

  • 19 / 1

Start / End Page

  • 15 -

PubMed ID

  • 33487168

Pubmed Central ID

  • PMC7831173

Electronic International Standard Serial Number (EISSN)

  • 1741-7007

International Standard Serial Number (ISSN)

  • 1741-7007

Digital Object Identifier (DOI)

  • 10.1186/s12915-020-00943-9


  • eng