Hominin History / Molecules
Interactive · Molecules

The Molecules That Made Us

Evolution doesn't only live in fossils and skulls — it's written into the proteins our cells build. Spin, zoom and restyle the real 3D structures behind some of the most human stories in our genome, starting with FOXP2, the so-called "language gene".

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Structures: RCSB Protein Data Bank & AlphaFold DB

Why these molecules?

Each protein below carries a chapter of the human story — a change of diet, a move to thin mountain air, a borrowed gene from an archaic cousin, or the deep machinery of speech. Pick one to load it in the viewer above.

FOXP2

FOXP2 The “language gene”

A transcription factor that switches other genes on and off in the developing brain and vocal circuitry. The human version differs from the chimpanzee’s by just two amino acids — T303N and N325S — fixed on our lineage after the split, and the gene carries signatures of positive selection. Mutations in it cause an inherited speech-and-language disorder. Neanderthals shared the same two human changes, so the truth is subtler than “the gene that gave us speech”.

HBA / HBB

Haemoglobin Oxygen, malaria & natural selection

The oxygen-ferrying protein of red blood cells: four globin chains cradling four iron-bearing haem groups. A single base change in the β-globin gene makes sickle haemoglobin (HbS) — one copy guards against malaria, two copies cause sickle-cell disease. Because malaria kept the protective allele common, HbS is the textbook example of natural selection still acting on living humans.

AMY1

Salivary amylase Starch, diet & copy number

The enzyme in saliva that begins breaking starch into sugar — the reason bread turns sweet as you chew. Humans typically carry many more copies of the AMY1 gene than chimpanzees do, and populations with starchy diets tend to carry the most: more gene copies mean more enzyme. It’s a striking case of recent dietary adaptation written in copy number rather than a single mutation.

EPAS1

EPAS1 / HIF-2α A gene borrowed from Denisovans

A master switch in the body’s response to low oxygen. A version of EPAS1 that lets Tibetans thrive above 4,000 m — without the thickened, dangerous blood lowlanders develop at altitude — was inherited from the Denisovans, an archaic human group known mostly from DNA. It is one of the clearest cases of adaptive introgression: a useful gene borrowed from another kind of human.

LCT

Lactase Milk-drinking into adulthood

The gut enzyme that digests lactose, the sugar in milk. In most mammals it switches off after weaning; in many humans a regulatory mutation keeps it on for life — “lactase persistence”. Different mutations arose independently in Europe and in African herding peoples within roughly the last 10,000 years: evolution responding to dairying, several separate times.

MC1R

MC1R Skin, hair & latitude

A receptor on pigment cells that helps decide whether they make dark eumelanin or lighter pheomelanin — a major control on skin and hair colour. As humans spread into cloudier, higher latitudes, variation here was shaped by the trade-off between UV protection and vitamin-D synthesis. Some Neanderthals carried their own reduced-function MC1R variant, hinting at pale skin or red hair.

How to read a protein structure

Proteins are long chains of amino acids that fold into precise 3D shapes — and the shape is the function. The default cartoon view simplifies the chain into ribbons: coiled helices and flat sheets show the protein's architecture, while the "rainbow" colouring runs from the start of the chain (blue) to the end (red), so you can trace its path.

Switch to sticks or spacefill to see individual atoms, or surface to see the molecule's outer shape — the contours that let it grip DNA, oxygen or a sugar. Crystal structures (four-character PDB codes like 2A07) are experimentally measured. AlphaFold models are computational predictions; with "Confidence" colouring, warmer regions are lower-confidence — often floppy, disordered stretches that don't hold one fixed shape.

These proteins belong to specific players in our family tree — the Denisovans behind the altitude gene, the Neanderthals who shared our FOXP2. Meet them on the interactive timeline.

Explore the family tree →
Sources & further reading
  1. Enard, W. et al. (2002). "Molecular evolution of FOXP2, a gene involved in speech and language." Nature 418. nature.com
  2. Stroud, J. C. et al. (2006). "Structure of the forkhead domain of FOXP2 bound to DNA." Structure 14 (PDB 2A07). rcsb.org/2A07
  3. Krause, J. et al. (2007). "The derived FOXP2 variant of modern humans was shared with Neandertals." Current Biology 17. cell.com
  4. Perry, G. H. et al. (2007). "Diet and the evolution of human amylase gene copy number variation." Nature Genetics 39. nature.com
  5. Huerta-Sánchez, E. et al. (2014). "Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA." Nature 512 (EPAS1). nature.com
  6. Jumper, J. et al. (2021). "Highly accurate protein structure prediction with AlphaFold." Nature 596. nature.com
  7. RCSB Protein Data Bank. rcsb.org · AlphaFold Protein Structure Database. alphafold.ebi.ac.uk
  8. 3Dmol.js — Rego & Koes (2015), Bioinformatics 31. 3dmol.org