RT Journal
A1 Xie, Dongying
A1 Ye, Pohao
A1 Ma, Yiming
A1 Zhao, Zhongying
T1 Pangenome analysis reveals families of ubiquitin-ligase adaptors as key genomic divergence drivers that lead to hybrid incompatibility
JF Genome Research 
JO Genome Research 
YR 2026 
FD March 01 
VO 36 
IS 3 
SP 506 
OP 521 
DO 10.1101/gr.280885.125 
UL http://genome.cshlp.org/content/36/3/506.abstract 
AB Understanding how genomic divergence drives biodiversity remains a central question in evolutionary biology. The nematodes Caenorhabditis briggsae and its sister species Caenorhabditis nigoni provide an ideal model system to address this question, as they exhibit extensive genomic divergence with limited gene flow from C. briggsae to C. nigoni. Despite previous comparative genomic studies, a comprehensive analysis of both conspecific and interspecific variations, and their potential impact on hybrid incompatibility, remains lacking. Here, we present a pangenome study of populations from both species, revealing that C. nigoni consistently possesses larger genomes and higher gene counts than C. briggsae. This difference primarily results from markedly larger interspecific unaligned regions in C. nigoni, which overlap significantly with C. nigoni intraspecific unaligned segments that are also substantially larger than those in C. briggsae. Moreover, the increased gene number in C. nigoni is largely owing to the expansion of species-specific dispensable gene families. Notably, both the inter- and intraspecific unaligned regions and the expanded dispensable genes in C. nigoni show a significant enrichment in rapidly evolving genes encoding Cullin-E3 ubiquitin-ligase adaptors, particularly F-box proteins, which are speculated to mediate immune and stress responses in nematodes. A detailed examination of a recently evolved F-box gene family (fbxn family), which includes a speciation gene Cni-neib-1, demonstrates extensive polymorphism among populations, which may contribute to hybrid incompatibility. Collectively, our findings underscore the significance of fast-evolving ubiquitination and protein degradation pathways in driving genomic divergence, and suggest a potential link between incompatible immunity and speciation.