The Human Glycome Project: Why Glycans Are the Third Revolution in Evolution

When the Human Genome Project finished mapping our DNA in 2003, it promised to explain what makes us human. Two decades later, we know that promise was only partly kept. DNA tells us what a cell could build, but almost nothing about what a cell is actually doing right now, or how its immune system is responding to the world. That gap between genetic code and lived biology is where glycans live, and it's why a growing body of glycobiology research treats them as a third layer of complexity that neither DNA nor proteins can account for on their own.

Glycans are complex sugar structures, chains of simple sugar units, that attach to proteins and lipids in a process called glycosylation. They are not genetic material and they are not proteins; they sit downstream of both, modifying how proteins fold, function, and communicate with other cells. Professor Gordan Lauc, co-founder of GlycanAge, has spent over three decades studying these structures and argues that glycosylation itself was a precondition for complex life. An initiative called the Human Glycome Project is now trying to map that layer with the same ambition the Human Genome Project once brought to DNA. "Glycans are the revolution in evolution which enabled multicellular life," says Prof. Gordan Lauc, co-founder of GlycanAge.

Want the fuller picture of what these sugar structures actually do in your body? Glycans: The Sugars That Reveal Your Biological Age and Immune Health breaks down how glycans work as a biomarker.

Why DNA and proteins weren't enough

The Human Genome Project decoded the genetic blueprint of a human being, but the blueprint alone could not explain how a single fertilised cell becomes a body with organs, tissues, and a coordinated immune system. Epigenetics offered a partial answer, showing genes can be switched on and off without any change to the underlying DNA sequence. But even genetics plus epigenetics leaves a gap: a human has roughly 20,000 genes compared to E. coli's 5,000, nowhere near enough to account for the difference in biological complexity between the two.

Glycosylation is what closes that gap, adding a layer of complexity between a gene's sequence and a protein's function that bacteria largely lack.

"At one point in evolution, when we were becoming multicellular, we invented glycosylation. We invented a network of interactions of dozens of proteins which work together to make a glycan structure, which then becomes part of a protein."

— Prof. Gordan Lauc, Co-Founder and CSO, GlycanAge; Professor of Biochemistry and Molecular Biology, University of Zagreb

Alternative glycosylation, attaching different glycan structures to the same site on a protein, functions much like a coding mutation, changing what the protein does; but unlike a mutation, it is inherited as a complex trait shaped by an entire regulatory network. Prof. Lauc's group demonstrated this directly in a study of mouse strains that became structurally and functionally distinct without a single genetic mutation, simply because the network governing glycosylation reshuffled itself.

The evolutionary leap: how glycosylation built multicellular life

Glycosylation's emergence coincides with one of the largest transitions in the history of life: the shift from single-celled to multicellular organisms. Bacteria carry far less complex glycosylation machinery, synthesising glycans that are shorter and structurally more primitive, while mammals evolved the capacity to build elongated, branched glycan structures with far greater informational capacity. That leap gave rise to the molecular machinery of intercellular communication that multicellular life depends on.

The immune system illustrates why this matters most directly: some core glycan structures are shared between microorganisms and human cells, shaping how the immune system distinguishes self from non-self, a process called immune tolerance.

"All of our cells are covered with glycans, a glyco-signature that acts like an identity card. There are core structures that are shared between microorganisms and human beings, which contribute to the process of immune tolerance — or, in some situations, the inability to assure tolerance, leading to a breach of immune tolerance."

— Prof. Salomé Pinho, GlycanTrigger Coordinator, i3S, University of Porto

The missing layer: glycans as biology's unmapped frontier

The Human Glycome Project is the research initiative dedicated to decoding this hidden layer of biology, positioned as the natural successor to the Human Genome Project and the wave of epigenetic research that followed it. Where the Human Genome Project mapped the genetic blueprint and epigenetics revealed how that blueprint gets switched on and off, the Human Glycome Project is attempting to map glycans themselves. Unlike genes, glycans are functional effectors: there is already substantial knowledge about what each specific glycan structure does biologically, which is part of why lifestyle changes can influence these structures.

The scale of this correlation with ageing is striking. In a large multi-omic study on a Whitehall cohort, researchers quantified more than 6,000 molecules across metabolomics, glycomics, genomics, and epigenomics. Among the top 20 molecules that correlated most strongly with chronological age, nine were IgG glycans, immunoglobulin G glycans, outnumbering every other molecular category except steroid hormones. This is the sense in which the Human Glycome Project represents unmapped territory: not a niche biomarker, but a systematic, population-scale signal of ageing biology that had gone largely undocumented until glycomics matured as a field.

What the Human Glycome Project means for the future of biology

The Human Glycome Project reframes glycans from an obscure biochemical curiosity into a foundational layer of biological information, on par with the genome and the epigenome. Genes encode evolutionary wisdom accumulated over millions of years; glycans sit closer to the present, integrating genetic, epigenetic, and environmental input into a structure that does functional work in the body, particularly in regulating inflammation through the immune system.

"I think it's going to be an explosion over the next decade, because now we have the technology, and we're going to have many studies investigating glycomics the way we've had for metabolomics, genomics, and proteomics. I think this next decade is going to be the glycomics decade."

— Prof. Samia Mora, MD, MHS, Associate Professor of Medicine, Harvard Medical School; Division of Preventive Medicine, Brigham and Women's Hospital

Three decades of glycobiology research, spanning more than 350 published scientific papers and collaborations with institutions including the University of Oxford, Harvard Medical School, and the University of Edinburgh, have moved glycans from an overlooked corner of cell biology to a recognised layer of biological regulation in its own right. The work of the Human Glycome Project continues that trajectory: not by replacing the genome or the epigenome, but by filling in the layer neither could explain on its own.

For readers who want to see how this evolutionary science translates into a measurable, individual signal, GlycanAge's biological age test applies these same IgG glycan principles at the personal level, tracking how an individual's immune-regulating glycan patterns shift over time. Order your test kit and see what your own glycans reveal.

Curious how the glycan biology behind human evolution shows up in your own immune system? Explore the GlycanAge test.

External sources

• International Human Genome Sequencing Consortium. The Human Genome Project. National Human Genome Research Institute; 2003.
  Link: https://www.genome.gov/human-genome-project

• Lauc G, Pezer M, Rudan I, Campbell H. Mechanisms of disease: the human N-glycome. Biochim Biophys Acta. 2016;1860(8):1574-82. doi:10.1016/j.bbagen.2015.10.016. PMID:26500099
  Link: https://pubmed.ncbi.nlm.nih.gov/26500099/