The Evolution of Lactose Tolerance — HHMI BioInteractive Video

Summary

This script explores the fascinating evolution of lactase persistence in humans, which allows some adults to digest milk unlike most mammals. It delves into the co-evolution of human biology and culture, starting with the domestication of animals and cultivation of crops around 10,000 years ago. The narrative follows the quest to understand lactase persistence, including genetic studies and archaeological evidence of early milk use. It highlights the strong selective advantage this trait provided in pastoral societies, exemplifying gene-culture co-evolution.

Takeaways

• 🧬 Humans evolved as hunter-gatherers for most of our history, but around 10,000 years ago, the domestication of animals and cultivation of crops began, impacting our biology.
• 🍼 Milk is a staple in many diets, but the ability of adults to digest it varies significantly across different populations, which is a fascinating study of human biology and culture co-evolution.
• 👶 All infant mammals can digest lactose, the main sugar in milk, with the help of the lactase enzyme, but most lose this ability as they grow older, becoming lactose intolerant.
• 🧪 Lactase persistence, the ability to digest lactose into adulthood, is linked to genetic mutations that were discovered by comparing DNA from lactase persistent and non-persistent individuals.
• 🌍 Geographic distribution of lactase persistence is uneven, with a majority of people in Europe being able to digest lactose, while in other regions, lactase persistence is less common.
• 🧬 Researchers found different genetic mutations for lactase persistence in European and African populations, indicating that this trait evolved independently in response to similar environmental pressures.
• 🧬 The mutation that enables lactase persistence in Europeans was identified as a T instead of a C at a specific non-coding position in the DNA.
• 🌿 Pastoralists, such as the Maasai and early Europeans, who domesticated animals for food, are more likely to have the lactase persistence trait, suggesting a cultural influence on genetic evolution.
• 🧪 Organic chemist Richard Evershed used chemical signatures to determine that ancient pots from Europe and Africa contained milk, providing archaeological evidence of early dairy use.
• ⏳ The spread of lactase persistence mutations in populations coincides with the archaeological evidence of the start of milk use, suggesting a strong selective advantage for those who could digest lactose.
• 💪 The selective advantage of lactase persistence was estimated to be around 5% to 10%, meaning that individuals with this trait had a significantly higher survival rate, likely due to better nutrition and reduced exposure to pathogens.

Q & A

What was the primary lifestyle of humans before the shift to agriculture about 10,000 years ago?

Humans primarily lived as hunter-gatherers, obtaining their food by hunting animals and gathering plants.

Why is the ability to digest lactose in adulthood considered a fascinating case study in co-evolution?

The ability to digest lactose in adulthood is a result of the interaction between human culture (the domestication of animals for milk) and human biology (the persistence of lactase production), illustrating how cultural practices can drive biological evolution.

What is the main sugar in milk and why is it significant?

The main sugar in milk is lactose. It is significant because most mammals lose the ability to digest it after infancy due to the cessation of lactase production, leading to lactose intolerance in adulthood.

What happens when a lactose intolerant adult consumes milk?

When a lactose intolerant adult consumes milk, the lactose passes undigested into the large intestine, where bacteria ferment it, causing symptoms like cramps, gas, and diarrhea.

What is the term for the minority of adults who can digest lactose and why is it important?

These adults are called 'lactase persistent' because their ability to produce lactase, the enzyme that breaks down lactose, continues beyond childhood and throughout their lives, allowing them to digest milk without adverse effects.

What was the purpose of Spencer Wells' lactose tolerance test?

The lactose tolerance test was conducted to determine whether Spencer Wells' body still produces lactase, which would indicate his ability to digest lactose as an adult.

What did geneticists find when they compared the lactase gene across lactase persistent and non-persistent people?

Geneticists did not find a change in the DNA sequence of the lactase gene itself that distinguished lactase persistent from non-persistent individuals. Instead, they discovered regulatory mutations affecting the lactase gene.

How did researchers identify the mutation responsible for lactase persistence in Europeans?

Researchers identified Finnish families with both lactase persistent and non-persistent members, compared DNA around the lactase gene, and discovered a one-base difference (a T instead of a C) in a non-coding position that causes lactase persistence.

What did geneticist Sarah Tishkoff discover about lactase persistence in African populations?

Sarah Tishkoff found that the European lactase persistence mutation barely existed in African samples. Instead, she discovered a different mutation in the Maasai population, indicating that lactase persistence evolved independently in different populations.

What evidence did Richard Evershed find regarding the use of milk in ancient cultures?

Richard Evershed found chemical signatures of milk fats in ancient pots from both European and African settlements, dating back 7,000 to 9,000 years ago, indicating that dairy use was prevalent in these early cultures.

How did the practice of dairying potentially drive the spread of lactase persistence mutations?

The practice of dairying provided a selective advantage for individuals with lactase persistence mutations, as they could digest milk and benefit from its nutritional content. This advantage could have led to an increase in the frequency of the mutation in populations that relied on milk.

What is the estimated selective advantage of lactase persistence, and how does it manifest?

The selective advantage of lactase persistence is estimated to be around 5% to 10%, meaning that individuals with this trait had a higher survival rate, which could accumulate over generations due to the nutritional benefits of being able to digest milk.

What is the significance of the gene-culture co-evolution in the context of lactase persistence?

The gene-culture co-evolution signifies that human biological evolution is deeply intertwined with cultural practices, such as dairying, which in the case of lactase persistence, drove the evolution of a genetic trait that conferred a survival advantage.

Outlines

00:00

🥛 The Evolution of Lactase Persistence

The script begins by setting the stage for a discussion on the evolution of human dietary habits, particularly the shift from a hunter-gatherer lifestyle to one involving agriculture and animal domestication around 10,000 years ago. It introduces the concept of lactase persistence, a genetic trait that allows some adults to digest lactose, a sugar found in milk. The script explains the biological process of lactose digestion in infants and the typical cessation of lactase production in most mammals after infancy, leading to lactose intolerance in adulthood. It then poses intriguing questions about the origins of lactase persistence in humans and sets the stage for an exploration of this genetic adaptation, starting with a lactose tolerance test at University College London.

05:01

🧬 Genetic Discovery of Lactase Persistence

This paragraph delves into the genetic research behind lactase persistence. It describes the process by which researchers identified a specific mutation in the lactase gene regulatory region that is associated with lactase persistence in Finnish families and other Europeans. The narrative follows the scientific journey, including the unexpected discovery that a different mutation is responsible for lactase persistence in the Maasai population of East Africa. The script highlights the independent evolution of this trait in different populations and the significance of this finding in understanding gene-culture co-evolution, where cultural practices like pastoralism have driven genetic changes in human populations.

10:03

🍶 Archaeological and Genetic Evidence of Early Dairying

The final paragraph of the script brings together archaeological and genetic evidence to explain how the practice of dairying may have driven the spread of lactase persistence. It describes how organic chemist Richard Evershed used chemical analysis to identify milk fats in ancient pottery, providing evidence of milk consumption dating back to the dawn of civilization. The script discusses how the dates of the spread of lactase persistence mutations correlate with the archaeological evidence of milk use, suggesting a strong selective advantage for lactase persistence in populations that practiced dairying. The narrative concludes with a discussion on the potential nutritional and health benefits of milk that could have contributed to the selection for lactase persistence, emphasizing the unique interplay between human biology and culture in shaping our genetic evolution.

Keywords

💡Hunter-gatherers

Hunter-gatherers refers to the lifestyle of early humans who subsisted by hunting and foraging for wild plants. This concept is central to the video's theme as it contrasts with the agricultural shift that led to the domestication of animals and the cultivation of crops, which in turn influenced human biology and culture.

💡Cultural changes

Cultural changes refer to the significant transformations in human societies, such as the shift from hunter-gathering to agriculture around 10,000 years ago. In the context of the video, these changes are highlighted as they had profound biological impacts on human species, including the development of lactase persistence.

💡Lactose

Lactose is the main sugar found in milk. The video explains that lactose is not easily absorbed by the body without the enzyme lactase, which is typically produced only during infancy. The script discusses how the ability to digest lactose beyond childhood is a fascinating example of the co-evolution of human biology and culture.

💡Lactase

Lactase is an enzyme that breaks down lactose into glucose and galactose, which can then be absorbed into the bloodstream for energy. The video emphasizes the importance of lactase in the context of lactose intolerance and lactase persistence, showing how the continued production of lactase in some adults is a significant biological adaptation.

💡Lactose intolerance

Lactose intolerance is a common condition where people lose the ability to digest lactose after infancy, leading to gastrointestinal symptoms when consuming milk. The script uses this term to describe the typical mammalian condition and to contrast it with the unusual human ability to digest lactose in some populations.

💡Lactase persistent

Lactase persistent individuals are those who continue to produce lactase into adulthood, allowing them to digest lactose without issue. The video discusses this as a minority trait that has significant implications for understanding human evolution and the interplay between biology and culture.

💡Geneticist

A geneticist is a scientist who studies genetics, the branch of biology concerned with the study of genes, genetic variation, and heredity. In the video, geneticist Dallas Swallow helps to demonstrate how to determine lactose tolerance and explores the genetic basis of lactase persistence.

💡Lactose tolerance test

The lactose tolerance test is a medical procedure used to determine an individual's ability to digest lactose. The video script describes Spencer Wells undergoing this test, which involves measuring blood glucose levels before and after consuming a lactose load.

💡Gene-culture co-evolution

Gene-culture co-evolution is a concept where genetic and cultural changes influence each other. The video uses this term to describe the mutual influence between the development of lactase persistence and the cultural practice of dairying, highlighting a rare but powerful example of this phenomenon.

💡Mutation

A mutation refers to a change in the DNA sequence. The video explains how specific mutations in the DNA regions that regulate the lactase gene have allowed some human populations to continue producing lactase into adulthood, providing a selective advantage in certain environments.

💡Pastoralists

Pastoralists are people who live primarily by keeping livestock, often in a nomadic or semi-nomadic manner. The video script discusses how pastoralist cultures, such as the Maasai and early Europeans, have independently developed lactase persistence, likely due to their reliance on milk from their animals.

Highlights

Humans evolved as hunter-gatherers, but around 10,000 years ago, cultural changes led to the domestication of animals and cultivation of crops.

Milk, a familiar food, is the main ingredient in many favorite dishes and is central to the study of human culture and biology co-evolution.

Infant mammals can digest milk due to the enzyme lactase, but most lose this ability as they age, becoming lactose intolerant.

A lactose tolerance test measures blood glucose levels to determine if lactase is still produced in adulthood.

Lactase persistence, the ability to digest lactose in adulthood, is prevalent in Northern Europe but less so in other regions.

Researchers discovered a one-base difference in DNA, a T instead of a C, that causes lactase persistence in Europeans.

Different lactase persistence mutations were found in African populations, such as the Maasai, indicating independent evolution.

Pastoralist cultures, such as the Maasai and early Europeans, are linked to the evolution of lactase persistence due to their reliance on cattle.

Archaeological evidence shows that dairy use dates back 9,000 years in Europe and the Middle East, aligning with the spread of lactase persistence mutations.

Chemist Richard Evershed used gas chromatography and mass spectrometry to find a chemical signature of milk fats in ancient pottery.

The selective advantage of lactase persistence is estimated to be around 5% to 10%, significantly impacting survival rates.

Milk is a rich source of protein and fat, offering a nutritional advantage that may have driven the spread of lactase persistence.

Milk's uncontaminated nature reduced exposure to pathogens, providing a survival advantage during times of food scarcity.

The evolution of lactase persistence is a rare example of gene-culture co-evolution, where biological evolution is intertwined with cultural practices.

Understanding human biological evolution requires insights into cultural evolution, highlighting the unique gene-culture co-evolutionary story of humans.

The study of lactase persistence exemplifies the complex interplay between genetics, culture, and survival advantages in human evolution.

Transcripts

[FOOTSTEPS]

[MUSIC PLAYING]

SPENCER WELLS: Only a small number of human beings

live like this today.

But from the time our species evolved some 200,000 years ago

until the not-too-distant past, all of us

lived as hunter-gatherers.

Then around 10,000 years ago, people

started domesticating animals for food,

living in settlements, and cultivating crops.

These cultural changes had profound biological impacts

on our species.

And you're about to encounter one surprising example.

It has to do with a familiar food.

[MUSIC PLAYING]

I'm talking about milk, the main ingredient

in some of our favorite things.

Almost all of us can digest it as babies,

but the story of how many adults can use it as a food

is a fascinating case study, a study of the co-evolution

of human culture and biology.

[MUSIC PLAYING]

All infant mammals can digest milk.

In fact, producing milk for babies

is a key trait that distinguishes mammals

from all other types of animals.

The main sugar in milk, lactose, can't easily

pass through the intestinal wall,

so cells here make an enzyme called

lactase, which breaks lactose into glucose and galactose.

These two simpler sugars can then

enter the bloodstream, where they can be used for energy.

Around the time young mammals stop drinking milk,

almost all of them stop making lactase,

so they lose their ability to digest milk.

They become lactose intolerant.

What typically happens when an adult mammal drinks milk,

it's not pretty.

The lactose goes undigested straight

through the small intestine to the large intestine.

Here, bacteria eat the sugar and can cause cramps, gas,

and diarrhea.

It's a bad idea to offer a bowl of milk to an adult cat.

We only know of one mammal species

in which some adults can drink milk without getting sick.

Yes, it's us.

Not all of us, but worldwide, about a third of adults

can digest lactose.

This minority is called lactase persistent

because their ability to produce the enzyme that breaks down

lactose persists beyond childhood and in fact,

throughout their lives.

How did lactase persistence come about?

Why does it occur only in some people?

I've come to University College London

to start my quest to find out.

Geneticist Dallas Swallow will show me

how to figure out whether someone

can digest the sugar in milk.

DALLAS SWALLOW: You're going to do a lactose tolerance test?

SPENCER WELLS: I am.

DALLAS SWALLOW: The idea is to look

to see what the level of glucose is

in the blood of the volunteer before the lactose load has

been taken.

SPENCER WELLS: After measuring my baseline glucose level,

I now have to chug a liter of milk.

DALLAS SWALLOW: You're allowed to breathe in between.

It's all right.

SPENCER WELLS: [SIGHING] Mm.

If my body is still making lactase,

my blood glucose will shoot up.

After I drank the milk, here is what happened.

No doubt about it, my lactase enzyme is still working.

DALLAS SWALLOW: Where do your family come from?

SPENCER WELLS: Britain on my father's side.

Denmark-- Holland-- on my mother's side.

But kind of northern Europe [INAUDIBLE]..

DALLAS SWALLOW: Northern Europe, okay.

You can see, first of all, that most people in Europe

are lactase persistent.

SPENCER WELLS: My family background makes sense.

In only a few regions is a large majority

of people lactase persistent.

In other parts of the world, few adults easily digest lactose.

What exactly is different about people

who are lactase persistent?

To get a clue, researchers looked at DNA.

They first compared the part of the lactase gene that

encodes the enzyme across persistent and non-persistent

people.

They didn't find a change in the DNA that

distinguished the two traits.

So what could explain the difference?

We know that genes, including lactase, are regulated--

turned on or off--

dialed up or down--

by other pieces of DNA that act like switches.

In search of a possible mutation in a lactase switch,

a research team identified Finnish families that had

members who were lactase persistent,

as well as those who weren't.

Statistical geneticist Joe Terwilliger

was part of the team.

JOE TERWILLIGER: We then looked to see

if they shared DNA around the region where

the gene was that we knew was affecting

the metabolism of lactose.

SPENCER WELLS: On chromosome 2, in and around the lactase gene,

a number of shared markers in the DNA

allowed Terwilliger and his colleagues

to home in on a segment of DNA likely to contain

the lactase persistence mutation.

By comparing this segment base by base

across lactase persistent and non-persistent individuals,

they discovered the critical one-base difference,

a T instead of a C at one non-coding position.

The researchers had made an important discovery.

They'd found a mutation that causes lactase persistence

in Finns and other Europeans.

Do all lactase persistent people carry this mutation?

DALLAS SWALLOW: I thought there would be one mutation,

and that would be it.

So we went off to study samples from Africa.

And to our surprise, we found that the mutation barely

existed.

SPENCER WELLS: Was a different mutation at work

on this continent?

Then a young professor, geneticist Sarah Tishkoff,

traveled to a number of African countries to find out.

SARAH TISHKOFF: We've now looked at Tanzania, Kenya,

and the Sudan, and Ethiopia.

And so we've really looked at a broad range of groups

mainly in eastern Africa at this point.

SPENCER WELLS: In one population,

the Maasai, Tishkoff and colleagues

found a different lactase persistence mutation

from the one in Europeans.

The two mutations had arisen independently

in two different populations, in each case providing adults

with the ability to digest milk.

Tishkoff was more than pleased.

SARAH TISHKOFF: Thrilled-- excited--

you rarely-- it's so unusual to actually find

a variant that appears to be correlated

with such an interesting trait.

SPENCER WELLS: What was special about both the Maasai

and the early Europeans that might

explain why they each independently evolved

this trait?

Both are pastoralists, people who

domesticated animals for food.

SARAH TISHKOFF: They adore their cows.

They're very possessive of their cows.

This is their monetary system.

Their wealth is determined by their cows.

The culture centers around the cow.

SPENCER WELLS: Was the evolution of lactase persistence

driven by drinking milk?

If so, can we find evidence of early milk

use in these cultures?

In Bristol, England, organic chemist Richard Evershed

is examining fragments of old pots to find out.

RICHARD EVERSHED: These look like they were probably

cooking parts-- like the ancient saucepan.

We actually select pottery from the body or the upper parts

of vessels because, obviously, fat

floats on the surface of water when

you start the cooking process.

SPENCER WELLS: Evershed has examined the fats trapped

in pots from ancient settlements across Europe and Africa

to determine if milk was on the paleo menu.

RICHARD EVERSHED: It is quite wondrous

to think that you are holding artifacts in your hands

that were made and then used by people just like us.

SPENCER WELLS: To figure out whether these pots once

held milk, Evershed first had to find a chemical signature

of milk fats.

He started analyzing all kinds of fats

from contemporary animals.

RICHARD EVERSHED: We go to farms where they're using

traditional farming methods--

raising animals on natural grazes and pastures

as far as possible.

SPENCER WELLS: Comparing the ratios of two carbon isotopes

in two kinds of molecules in fats,

Evershed watched the measurements pour in.

RICHARD EVERSHED: I sat at my desk with one of my students.

And we were looking at some data.

And we started to sort of see patterns in the data.

SPENCER WELLS: Clustering in one part of the plot

were body fats from pigs.

[PIG SQUEALING]

In another region were body fats from ruminants, such as cows.

[COW MOOING]

But there was more.

RICHARD EVERSHED: I can remember the moment,

and it's as clear as day when we sat there.

There was these points disappearing off

the bottom of the graph.

They were the milk fats.

SPENCER WELLS: Evershed now had a tool

to look for evidence of milk in the ancient pots.

He hoped that the tight pores of the pottery material

would preserve the milk fats.

To find out, his team grinds up potsherds and analyzes them

with gas chromatography and mass spectrometry,

just as they did with present-day animal samples.

Evershed's detective work paid off.

Right where contemporary milk fat showed up,

there was now data from ancient pots.

They once contained milk.

African settlements 7,000 to 5,000 years ago

were using dairy.

And potsherds from Europe and the Middle East

showed milk use 9,000 years ago, the oldest ever discovered.

The dates reach back almost to the dawn of civilization.

Geneticists can date the origins of mutations by analyzing DNA.

Remarkably, the dates from when the European and African

lactase persistence mutations first spread in populations

are a good match with the archeological evidence

of when people first started using milk in these regions.

How did dairying drive the spread

of the lactase persistence mutations?

Mutations, of course, occur at random.

So before humans kept dairy animals,

if a mutation arose that maintained lactase production,

it could have vanished from the population.

Without milk around, there's no known advantage

for the mutation.

But if such a mutation existed when we started dairying,

then it could have increased in frequency in the population

because lactase persistence now provided a selective advantage.

I spoke with Mark Thomas to find out just how

powerful that advantage was.

MARK THOMAS: Mind-bendingly strong--

the estimates put it somewhere around 5% or 10%.

Let's just say that it's 5%.

What that means is that for every 100 people

who would've survived without this trait,

105 would've survived with this trait.

[INTERPOSING VOICES]

And that's every generation.

And it goes a generation-- generation.

You know how quickly generations happen.

SPENCER WELLS: And why?

MARK THOMAS: I don't know.

SPENCER WELLS: [LAUGHTER]

MARK THOMAS: I mean, look, I've got some ideas.

SPENCER WELLS: So what are your ideas?

MARK THOMAS: Naturally, we have to start first with just

basic nutritional facts.

So milk is very protein and fat rich.

Both are good for us.

The protein in milk is of the highest quality.

It's the only food that we are aware of that

was produced with the intention of being consumed.

SPENCER WELLS: Mm-hm.

MARK THOMAS: All other foods generally

want to avoid being consumed--

SPENCER WELLS: [LAUGHTER]

MARK THOMAS: --whether consciously or otherwise.

SPENCER WELLS: That's true.

That's true, yeah.

MARK THOMAS: Milk is a relatively uncontaminated

fluid.

And so it reduces the exposure to pathogens and parasites.

You have these populations that are

moving into northern Europe that are primarily

not lactase persistent.

Now, imagine your crops fail.

Now you become entirely dependent on your milk.

If you are in a famine situation--

so you are borderline starvation--

and you eat something that gives you diarrhea,

you're probably going to die.

And that's exactly the thing that's

going to happen to these people because they've got nothing

else to eat, and they're eating more and more effectively

toxic foods.

So I suspect that that's the real times that

sorted out the lactase persistent

from the lactase nonpersistent.

SPENCER WELLS: While the exact selective advantage

of lactase persistence is still being debated,

it's clear that the nature of this selection was unusual.

It's a rare but powerful case of what's called a gene culture

co-evolution.

MARK THOMAS: To understand our biological evolution absolutely

requires an understanding of our cultural evolution as well.

And that means that the human story is more a gene

culture co-evolutionary story than it is

for any other species on Earth.

[MUSIC PLAYING]