Multi-regional comparative N-glycomics reveals both spatial and phylogenetic gradients in mammalian brain N-glycome complexity

Authors

Thomas Klarić¹ , Ivan Gudelj¹ , Gabriel Santpere² , André Sousa³ , Mislav Novokmet⁴ , Frano Vučković⁴ , Shaojie Ma¹ , Ivona Bečeheli⁴ , Chet Sherwood⁵ , John Ely⁶ , Patrick Hof⁷ , Djuro Josić⁸ , Gordan Lauc⁴ , Nenad Sestan¹

1. Yale School of Medicine
2. Universitat Pompeu Fabra
3. University of Wisconsin Madison
4. Genos, Zagreb, Croatia
5. The George Washington University
6. MAEBIOS, Alamogordo, USA
7. Icahn School of Medicine at Mount Sinai
8. Brown University

Conference / event

Federation of European Neuroscience Societies (FENS) regional meeting 2023, May 2023 (Algarve, Portugal)

Poster summary

Comparative “omics” studies have revealed unique aspects of human neurobiology, yet an evolutionary perspective of the brain N-glycome is lacking. Here, we performed multi-regional characterization of rat, macaque, chimpanzee, and human brain N-glycomes using chromatography and mass spectrometry, then integrated these data with complementary glycotranscriptomic data. We found that in primates the brain N-glycome has evolved more rapidly than the underlying transcriptomic framework, providing a means for generating additional inter-species diversity. We show that brain N-glycome evolution in hominids has been characterized by a global increase in complexity and a shift towards increased usage of α(2-6)-linked N-acetylneuraminic acid. As a result of overlapping anatomical and phylogenetic gradients in complex N-glycan abundance, peak N-glycome complexity was found in the hominid cortical regions. We hypothesize that this increased diversity and complexity of sugar modifications on neural N-glycoproteins contributed to the emergence of novel cognitive functions, including those unique to the human neocortex.

Keywords

Brain, N-glycome, Evolution, N-glycomics, N-glycosylation, N-glycans

Research areas

Anatomy and Physiology, Biological Sciences, Neuroscience, Molecular and Cellular Biosciences, Evolutionary Biology

References

No data provided

Funding

No data provided

Supplemental files

1. bioRxiv Manuscript   Download

Additional information

Competing interests

The authors declare the following competing interests: GL is the founder and owner of Genos Ltd, a private research organization that specializes in high-throughput glycomic analysis and has several patents in this field. TK, IG, MN, FV, and IB are currently or were employees of Genos Ltd while participating in this research project.

Data availability statement

The datasets generated during and / or analyzed during the current study are available from the corresponding author on reasonable request.

Creative Commons license

Copyright © 2023 Klarić et al. This is an open access work distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.