️ Episode 129: Structural variation and diversification of the NPIP gene family from the human pangenome

In this episode of PaperCast Base by Base, we explore how long-read sequencing technologies reveal the structural variation, evolutionary pressures, and expression patterns of the NPIP gene family, one of the most positively selected gene families in humans and African apes.

Study Highlights:
Using long-read assemblies of 169 human haplotypes, researchers discovered extreme variability in NPIP loci organization and identified both fixed and polymorphic paralogs. They observed ongoing positive selection acting on specific NPIP copies, as well as large inversion polymorphisms and frequent gene conversion events shaping the genomic landscape. Long-read RNA sequencing enabled the construction of paralog-specific gene models, with more than half of the predicted protein isoforms previously undocumented. Expression analysis revealed that certain NPIP paralogs show brain-enriched patterns, while others maintain testis-specific expression, suggesting lineage-specific neofunctionalization.

Conclusion:
This study highlights the dynamic evolutionary trajectory of the NPIP gene family and provides a foundation for linking its variation to human phenotypes and disease.

Reference:
Dishuck, P.C., Munson, K.M., Lewis, A.P., Dougherty, M.L., Underwood, J.G., Harvey, W.T., Hsieh, P., Pastinen, T., & Eichler, E.E. (2025). Structural variation, selection, and diversification of the NPIP gene family from the human pangenome. *Cell Genomics*, 5, 100977. https://doi.org/10.1016/j.xgen.2025.100977

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

Support:
If you'd like to support Base by Base, you can make a one-time or monthly donation here: https://basebybase.castos.com/

Keywords: NPIP gene family, human pangenome, positive selection, structural variation, long-read sequencing