Vision-related convergent gene losses reveal SERPINE3's unknown role in the eye

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung


  • Henrike Indrischek - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Juliane Hammer - , Center for Regenerative Therapies Dresden (CRTD) (Autor:in)
  • Anja Machate - , Center for Regenerative Therapies Dresden (CRTD) (Autor:in)
  • Nikolai Hecker - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Bogdan Kirilenko - , Senckenberg Gesellschaft für Naturforschung (Autor:in)
  • Juliana Roscito - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Stefan Hans - , Center for Regenerative Therapies Dresden (CRTD) (Autor:in)
  • Caren Norden - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Michael Brand - , Center for Regenerative Therapies Dresden (CRTD) (Autor:in)
  • Michael Hiller - , Senckenberg Gesellschaft für Naturforschung (Autor:in)


Despite decades of research, knowledge about the genes that are important for development and function of the mammalian eye and are involved in human eye disorders remains incomplete. During mammalian evolution, mammals that naturally exhibit poor vision or regressive eye phenotypes have independently lost many eye-related genes. This provides an opportunity to predict novel eye-related genes based on specific evolutionary gene loss signatures. Building on these observations, we performed a genome-wide screen across 49 mammals for functionally uncharacterized genes that are preferentially lost in species exhibiting lower visual acuity values. The screen uncovered several genes, including SERPINE3, a putative serine proteinase inhibitor. A detailed investigation of 381 additional mammals revealed that SERPINE3 is independently lost in 18 lineages that typically do not primarily rely on vision, predicting a vision-related function for this gene. To test this, we show that SERPINE3 has the highest expression in eyes of zebrafish and mouse. In the zebrafish retina, serpine3 is expressed in Müller glia cells, a cell type essential for survival and maintenance of the retina. A CRISPR-mediated knockout of serpine3 in zebrafish resulted in alterations in eye shape and defects in retinal layering. Furthermore, two human polymorphisms that are in linkage with SERPINE3 are associated with eye-related traits. Together, these results suggest that SERPINE3 has a role in vertebrate eyes. More generally, by integrating comparative genomics with experiments in model organisms, we show that screens for specific phenotype-associated gene signatures can predict functions of uncharacterized genes.


Frühes Online-Datum21 Juni 2022
PublikationsstatusVeröffentlicht - Juni 2022

Externe IDs

Scopus 85133889733
unpaywall 10.7554/elife.77999
ORCID /0000-0003-0283-0211/work/142257346