Markers / Adaptation
The body your ancestors’ world built
Human populations are genetically very similar, and the places where they are not similar are almost all places where the environment pushed. Sunlight shaped skin. Malaria shaped blood. Farming shaped digestion, and crowds shaped immunity. These are the 38 positions where that shows most clearly, what each one did, and what changed underneath it afterwards.
One thing to be clear about before anything else. Every number here is a fact about a population, never about a person. A variant being common somewhere tells you the variant is common there. Reading it backwards, from a genotype to who somebody is, is the mistake most of this industry is built on, and with a few dozen positions it is wrong often enough to be worthless.
The four turns
An adaptation is a deal struck with a particular world. The deals in your genome were struck before four of them came along, each of which improved the view and made the way back down harder.
- Fireabout a million years ago
Cooking made food cheaper to digest and freed the energy that a large brain runs on. The earliest secure traces of burning at a human site are roughly a million years old.
- Farmingthe last 12,000 years
Grain, milk, settlement, crowds and the diseases crowds carry. Most of the adaptations a consumer chip can read are younger than this, which is why they still differ so sharply between populations.
- Industryroughly the last two centuries
Indoor work, heated buildings, refined food, cheap salt and sugar, tobacco at scale, and a collapse in infectious disease. This is where most of the deals in your genome came undone.
- The screenthe last fifteen years
Light at midnight and an attention market. Smartphone ownership among American adults went from 35 per cent in 2011 to 91 per cent in 2025, which is not enough time for anything in your DNA to have responded.
The four turns are the frame of Spiral Staircase: How Your Ancient Body Navigates the Modern World. Spiral Staircase is written by the same author as this site. The book and its sources.
Where humanity divides most sharply
The six positions in this panel with the widest gap between any two ancestry groups in how often the version is carried, out of the 2,504 people sequenced by the 1000 Genomes Project.
| Position | Gene | What it does | Widest gap |
|---|---|---|---|
| rs2814778 | ACKR1 | Duffy-null: the strongest population difference in the human genome | 99 points |
| rs1800414 | OCA2 | Lighter skin, the East Asian route | 85 points |
| rs6058017 | ASIP | The pigment switch that works in the opposite direction | 75 points |
| rs3184504 | SH2B3 | One variant, coeliac disease, blood pressure and defence against bacteria | 71 points |
| rs7041 | GC | The vitamin D carrier protein, second marker | 66 points |
| rs12785878 | DHCR7 | How much vitamin D your skin can make | 63 points |
Sunlight and vitamin D
Skin has to let in enough ultraviolet light to make vitamin D, and block enough to protect the folate in your blood. The right answer depends entirely on where you live, so it changed every time people moved.
| Position | What it is | Why it spread | What changed |
|---|---|---|---|
| rs1800414 OCA2 | Lighter skin, the East Asian route Europe and East Asia both evolved lighter skin after moving away from the tropics, and they did it with different genes. This is the East Asian one. It is a clean demonstration that the same environmental problem was solved twice, independently. | well established The environmental pressure behind this variant is documented and not in serious dispute. | Industry Chapter 19 |
| rs6058017 ASIP | The pigment switch that works in the opposite direction ASIP tells pigment cells to make the lighter red-yellow pigment instead of the dark brown one. Unlike most pigmentation variants studied in Europeans, this one varies strongly across African and South Asian populations too. | well established The environmental pressure behind this variant is documented and not in serious dispute. | Industry Chapter 19 |
| rs12785878 DHCR7 | How much vitamin D your skin can make DHCR7 controls the supply of the precursor your skin turns into vitamin D under ultraviolet light. Variants here rose in frequency in northern populations, which is what you would expect where sunlight is scarce for half the year. | well established The environmental pressure behind this variant is documented and not in serious dispute. | Industry Chapter 19 |
| rs10741657 CYP2R1 | Turning vitamin D into the usable form CYP2R1 is the liver enzyme that activates vitamin D after your skin makes it. It is the second of the two strongest common influences on your measured level. | well established The environmental pressure behind this variant is documented and not in serious dispute. | Industry Chapter 19 |
| rs7041 GC | The vitamin D carrier protein, second marker A second position in the gene for the protein that transports vitamin D in blood. The two common forms bind it with different strength, which changes both your measured total and how much is actually free to use. | a strong case, not settled There is a clear signal of recent selection and a widely favoured explanation for it, which is not the same as a proven one. | Industry Chapter 19 |
| rs2228570 VDR | The vitamin D receptor, FokI Having vitamin D and responding to it are different things. This change alters where the receptor protein starts, producing a slightly longer or shorter version, and the shorter one is somewhat more active. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | Industry Chapter 19 |
Infection, and the cost of fighting it
For most of human history the commonest way to die young was infection. An immune system tuned to win those fights is tuned for a world that, in rich countries, no longer exists.
| Position | What it is | Why it spread | What changed |
|---|---|---|---|
| rs2814778 ACKR1 | Duffy-null: the strongest population difference in the human genome Plasmodium vivax malaria gets into red blood cells through the Duffy protein. A single change switches that protein off in red cells, and the parasite loses its doorway. It sits above 95 per cent across West and Central Africa and near zero in Europe and Asia, which makes it the most sharply differentiated common variant known in our species. | well established The environmental pressure behind this variant is documented and not in serious dispute. | Industry Chapter 37 |
| rs9264942 HLA-C | How much HLA-C you display, and HIV control HLA molecules hold up fragments of what is inside your cells for immune inspection. This position controls how much HLA-C is displayed, and people who display more of it control HIV infection considerably better without treatment. It is one of the clearest single-variant effects on any infectious disease. | a strong case, not settled There is a clear signal of recent selection and a widely favoured explanation for it, which is not the same as a proven one. | Industry Chapter 20 |
| rs4833095 TLR1 | How loudly your innate immune system shouts Toll-like receptors are the immune system's first alarm, recognising bacteria within minutes. This variant lowers the response. It shows one of the strongest signals of recent selection in Europeans, and the likely trade is a quieter alarm in exchange for less collateral inflammation. | a strong case, not settled There is a clear signal of recent selection and a widely favoured explanation for it, which is not the same as a proven one. | Industry Chapter 18 |
| rs2476601 PTPN22 | The autoimmunity variant that Europeans have and others do not PTPN22 sets the threshold at which immune cells activate. The variant version lowers it. It is a risk factor for rheumatoid arthritis, type 1 diabetes, lupus and several other autoimmune conditions, it is carried by roughly one European in ten, and it is essentially absent from East Asian and African populations. Whatever it was useful against, it is now a liability. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | Industry Chapter 18 |
| rs11209026 IL23R | A protective variant for Crohn's disease Most variants raise risk. This one lowers it, substantially, for Crohn's disease and for psoriasis and ankylosing spondylitis. It is carried by about one European in sixteen and is essentially absent elsewhere. It also pointed drug developers straight at the IL-23 pathway, which is now the target of several real medicines. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | Industry Chapter 12 |
| rs2066844 NOD2 | NOD2, the first Crohn's gene ever found NOD2 senses a fragment of bacterial cell wall inside your own cells. The variant version senses it less well, and the gut's relationship with its bacteria goes wrong. This was the first gene ever linked to a common inflammatory disease by genetics, and like PTPN22 it is a European variant, absent from East Asian populations where Crohn's disease is caused differently. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | Industry Chapter 12 |
| rs3184504 SH2B3 | One variant, coeliac disease, blood pressure and defence against bacteria A striking example of one change doing several things at once. The same variant raises risk of coeliac disease, type 1 diabetes and higher blood pressure, and it also produces a stronger response to bacterial infection. The favoured explanation is that the infection benefit was worth the rest, in a world where infection killed you young. | a strong case, not settled There is a clear signal of recent selection and a widely favoured explanation for it, which is not the same as a proven one. | Industry Chapter 18 |
| rs9271366 HLA-DRB1 | The strongest genetic risk factor for multiple sclerosis This tags an immune tissue type that is the largest single genetic contributor to multiple sclerosis risk. MS also has one of the sharpest latitude gradients of any disease, rising with distance from the equator, which is one of the reasons vitamin D keeps coming up in the research. | a strong case, not settled There is a clear signal of recent selection and a widely favoured explanation for it, which is not the same as a proven one. | Industry Chapter 18 |
| rs2228145 IL6R | The interleukin-6 receptor, and a drug target found by genetics IL-6 is a central inflammation signal. This variant shifts receptors off cell surfaces into the blood, which dampens the signal, and carriers have a slightly lower risk of coronary heart disease. That finding is a large part of why IL-6 blockade was pursued as a heart drug at all. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | Industry Chapter 20 |
| rs1205 CRP | Your baseline C-reactive protein CRP is the inflammation marker most often measured in a blood test. Part of your baseline is genetic rather than a reflection of how inflamed you are, which matters when a doctor reads the number. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | Industry Chapter 20 |
| rs1800629 TNF | Tumour necrosis factor, the inflammation dial TNF is one of the body's strongest inflammatory signals, and blocking it is the basis of several major drugs for rheumatoid arthritis and inflammatory bowel disease. This promoter variant is associated with producing more of it. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | Industry Chapter 20 |
| rs1143634 IL1B | Interleukin-1 beta, the fever signal IL-1 beta is the molecule that raises your body temperature during infection. Fever is a defence, not a symptom, and this variant is associated with producing more of the signal that triggers it. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | Industry Chapter 20 |
What your ancestors ate
Fats, folate and the chemistry of plants. Populations that farmed, that fished, or that herded ended up building different enzymes for the same jobs.
| Position | What it is | Why it spread | What changed |
|---|---|---|---|
| rs174546 FADS1 | Turning plant fats into the ones your brain runs on Your brain needs long-chain omega-3 and omega-6 fats. You either eat them ready-made, from fish and organ meat, or you build them from the short ones in plants. FADS1 does the building, and the efficient version swept through farming populations that ate mostly plants. Populations that kept eating fish never needed it, and Greenlandic Inuit carry a different version entirely, adapted the opposite way. | well established The environmental pressure behind this variant is documented and not in serious dispute. | Farming Chapter 13 |
| rs1801394 MTRR | The other folate gene, MTRR MTRR keeps the enzyme that recycles homocysteine back into methionine running, using vitamin B12. It is usually reported next to MTHFR, and it attracts some of the same overreach. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | Farming Chapter 4 |
Insulin, and a food supply that changed
How much insulin the pancreas puts out, and when. These variants differ between populations and were mapped through type 2 diabetes, a disease that was rare before the food supply changed.
| Position | What it is | Why it spread | What changed |
|---|---|---|---|
| rs13266634 SLC30A8 | The zinc transporter inside insulin granules Insulin is stored in the pancreas packed around zinc, and this transporter loads the zinc in. The variant version is associated with lower risk of type 2 diabetes. Unusually, rare mutations that break the gene completely are protective too, which is why it became a drug target. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | Industry Chapter 13 |
| rs7756992 CDKAL1 | CDKAL1 and how much insulin you release One of the first type 2 diabetes variants found, and one of the few that replicates in every population tested. It acts on how much insulin the pancreas puts out rather than on how well the body responds to it. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | Industry Chapter 13 |
| rs2237892 KCNQ1 | The diabetes variant that Europe nearly missed KCNQ1 was found by studying Japanese populations, not European ones, and it is one of the strongest type 2 diabetes signals in East Asia. It is a reminder that a genetics built only on European samples finds only the variants Europeans have, which is a real and ongoing problem in the field. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | Industry Chapter 13 |
| rs5219 KCNJ11 | KCNJ11, the channel that sulfonylurea drugs act on This potassium channel is the trigger that tells a pancreatic cell to release insulin. It is also exactly what the sulfonylurea class of diabetes drugs binds to, which makes this one of the few diabetes variants with a direct line to treatment. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | Industry Chapter 13 |
Cold
Staying warm costs energy. Populations that wintered in the north did it partly with tissue that burns calories as heat, which is much less useful in a heated building.
| Position | What it is | Why it spread | What changed |
|---|---|---|---|
| rs1800592 UCP1 | Brown fat, the tissue that burns calories as heat Brown fat does something unique: it uncouples the process that normally makes energy and releases the result as heat instead. It is how a baby stays warm, it is far more active in people who spend time in the cold, and UCP1 is the protein that does the uncoupling. | a strong case, not settled There is a clear signal of recent selection and a widely favoured explanation for it, which is not the same as a proven one. | Industry Chapter 25 |
A chemical environment that keeps changing
The liver evolved to clear what plants and smoke put into people. It now also handles drugs, solvents and the products of charred meat, which arrived far too recently to have shaped anything.
| Position | What it is | Why it spread | What changed |
|---|---|---|---|
| rs1799930 NAT2 | Fast or slow acetylator NAT2 clears a specific class of chemicals: several drugs, and the compounds formed when meat is charred. Roughly half of Europeans are slow acetylators and clear them sluggishly. The frequency shifted as populations took up farming, and it is one of the best documented cases of diet reshaping a detoxification gene. | well established The environmental pressure behind this variant is documented and not in serious dispute. | Farming Chapter 14 |
| rs1695 GSTP1 | One of the enzymes that mops up reactive chemicals Glutathione S-transferases attach a handle to reactive molecules so the body can throw them out. They handle smoke, cooked food, industrial solvents and the by-products of your own metabolism. This is the most studied position in the family. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | Industry Chapter 14 |
| rs4880 SOD2 | The antioxidant enzyme inside your mitochondria Making energy from oxygen leaks reactive oxygen. SOD2 is the enzyme that clears it, and it has to be imported into the mitochondrion to work. This change alters the import signal, so the two versions arrive at different rates. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | Industry Chapter 35 |
Salt, fat and blood pressure
Holding on to salt and water was the right instinct for almost all of human history. So was storing fat. Neither is an advantage in a shop.
| Position | What it is | Why it spread | What changed |
|---|---|---|---|
| rs662799 APOA5 | Triglycerides, and how sharply they respond to diet APOA5 controls how fast triglyceride-rich particles are cleared from blood. The variant version clears them more slowly, and it is around three times more common in East Asian than European populations, which is part of why triglyceride patterns differ between them. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | Industry Chapter 8 |
| rs12740374 SORT1 | SORT1, the LDL variant whose mechanism was actually solved Most common variants are found by statistics and their mechanism stays unknown. This one was chased all the way down: it creates a binding site for a liver transcription factor, changing how much SORT1 the liver makes, which changes how much LDL cholesterol the liver clears. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | Industry Chapter 8 |
| rs1799983 NOS3 | The enzyme that tells blood vessels to relax NOS3 makes nitric oxide in the lining of your blood vessels, which is the signal that widens them. It is the pathway nitrate-rich foods like beetroot act on, and the one that several blood pressure drugs work through. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | Industry Chapter 8 |
| rs5186 AGTR1 | The salt-and-water system, and why it now works against us The renin-angiotensin system evolved to hold on to salt and water, which was the right instinct for almost all of human history. In an environment of abundant salt it contributes to high blood pressure, and it is the system that ACE inhibitors and angiotensin blockers act on. | a strong case, not settled There is a clear signal of recent selection and a widely favoured explanation for it, which is not the same as a proven one. | Industry Chapter 17 |
| rs734553 SLC2A9 | Uric acid, and why humans keep so much of it Most mammals break uric acid down. Our ancestors lost that enzyme, and we retain uric acid instead, which is why humans get gout and almost nothing else does. Uric acid is a useful antioxidant and may have helped store fat from fruit, but in a world of beer, sugar and meat it crystallises in joints. SLC2A9 is the kidney transporter that decides how much you keep. | a strong case, not settled There is a clear signal of recent selection and a widely favoured explanation for it, which is not the same as a proven one. | Industry Chapter 17 |
Light, dark and sleep
The clock in your body is set by light. It evolved under one sunrise a day and no other bright light at all.
| Position | What it is | Why it spread | What changed |
|---|---|---|---|
| rs1801260 CLOCK | Morning or evening person CLOCK is a core gene of the circadian machinery that keeps your body on a roughly 24-hour cycle. The variant version is associated with going to bed later and preferring evenings. In an environment of electric light and indoor work, a late clock stops being a preference and becomes a mismatch. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | The screen Chapter 23 |
| rs73598374 ADA | How deeply you sleep Adenosine is the molecule that builds up while you are awake and makes you feel sleepy, and it is what caffeine blocks. This variant slows the enzyme that breaks adenosine down, so sleep pressure builds higher, and carriers show measurably more deep slow-wave sleep. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | Industry Chapter 23 |
Pressures with no evolutionary history
Tobacco is about four hundred years old outside the Americas, and the attention economy is about fifteen. Nothing in your DNA is an adaptation to either. These variants are ancient machinery being pulled by something new.
| Position | What it is | Why it spread | What changed |
|---|---|---|---|
| rs1800497 ANKK1 | Dopamine receptor density, the Taq1A variant The reward system evolved to make you chase scarce things: sugar, fat, salt, status, novelty. This variant is associated with fewer dopamine D2 receptors in the striatum, and it has been studied in addiction and in the pull of highly palatable food. It is the mismatch argument in a single gene. | Not an adaptation to anything The thing this variant responds to arrived far too recently to have shaped it. Ancient machinery, new pull. | The screen Chapter 30 |
| rs1051730 CHRNA3 | How many cigarettes a day, if you smoke Sitting in the same nicotine receptor cluster as the dependence variant, and inherited with it. Its effect is measured directly in cigarettes per day, and through that in lung cancer and emphysema risk. Nothing about this was shaped by evolution: tobacco arrived a few hundred years ago and found a receptor system built for something else. | Not an adaptation to anything The thing this variant responds to arrived far too recently to have shaped it. Ancient machinery, new pull. | Industry Chapter 10 |
| rs1042713 ADRB2 | The airway receptor that asthma inhalers act on Beta-2 receptors relax the smooth muscle around your airways. They are what a blue reliever inhaler targets. This variant changes how the receptor behaves after repeated stimulation, which is why it has been studied for asthma treatment response. | nobody knows The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing. | Industry Chapter 10 |
Common questions
Why do some genetic variants differ so much between populations?
Because the environment differed. Sunlight, malaria, diet, altitude and cold all made one version of a gene worth having in one place and not in another, and a few thousand years is enough for that to show. The clearest case is rs2814778 in ACKR1: switching off the Duffy protein blocks the doorway Plasmodium vivax uses to enter red blood cells, and it is carried by almost everybody of West and Central African descent and almost nobody else.
Does carrying a variant common in one population tell you your ancestry?
No. A variant being common in a group is a fact about the group. Reading it backwards, from one genotype to where somebody is from, is wrong often enough with a few dozen positions to be worthless. Ancestry is estimated from hundreds of thousands of positions at once, and even then it is a statement about probability.
What is evolutionary mismatch?
A body tuned to one set of conditions living in another. It is most visible where selection was strongest, because a variant that paid in one environment does not automatically pay in the next. Salt retention was the right instinct for almost all of human history and is not an advantage in a supermarket.
Do we know why every one of these variants spread?
No, and this page says so for each one. Of 38 adaptation markers, the environmental explanation is well established for some, a strong but unsettled case for others, and genuinely unknown for many. PTPN22 rs2476601 is carried by about one European in ten and is essentially absent from East Asian and African populations, and nobody knows what it was worth having for.
Can a home DNA test read these positions?
Most of them, yes. Every position here is common enough for a genotyping array to call reliably, and if you have tested with 23andMe, AncestryDNA, MyHeritage, Family Tree DNA or TellMeGen, the raw data file you already own very likely contains it.
Which of these do you carry?
If you have taken a consumer DNA test, most of these positions are already in the raw file you own. Sequencings reads it in your browser, resolves which strand your testing company reported each position from, and tells you how many of the 2,504 people in the reference panel carry what you carry. The file is never uploaded.