Dr. Sarah Tishkoff on Human Genetic Diversity

Uploaded by NIGMS on 10.09.2010

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Machalek: Dr. Sarah Tishkoff is a geneticist at the University of Pennsylvania.

Machalek: She studies genes from humans that have changed over time.

Machalek: She focuses her work in Africa,

Machalek: where humans have lived the longest amount of time

Machalek: and so by looking at people living there today,

Machalek: she can get the most complete record of how human genes have changed over time.

Machalek: Dr. Tishkoff, why is it important to study

Machalek: how the human genome has changed over time?

Tishkoff: Well, by studying variation in modern populations,

Tishkoff: we can make inferences about past demographic and evolutionary events.

Tishkoff: So if we want to learn something about when and where did modern humans evolve

Tishkoff: and learn more about the origins of different populations,

Tishkoff: we want to understand why some diseases are more common

Tishkoff: in certain populations than others,

Tishkoff: we can use evolutionary approaches to try to identify

Tishkoff: genetic variants that play a role in disease,

Tishkoff: because in some cases it is thought that genetic variants

Tishkoff: that cause some people to be at risk for disease in modern populations

Tishkoff: may have been adaptive in past populations.

Tishkoff: So, for example, in hunter/gatherer populations

Tishkoff: that went through periods of fasting or famine,

Tishkoff: it may have been advantageous to have a genetic variant

Tishkoff: that enabled them to store fat

Tishkoff: or to have a very rapid increase in sugar in their blood.

Tishkoff: However, in modern populations the same genetic variant

Tishkoff: could be maladaptive and result, for example, in diabetes.

Machalek: I know that one of your research projects focuses

Machalek: on the genetics behind why some adults can digest milk

Machalek: and others can't and that you looked at more than 400 Africans

Machalek: in more than 40 different ethnic groups

Machalek: and discovered three genetic variations

Machalek: that allowed them to drink milk, to digest milk.

Machalek: Can you explain the significance of this issue and your findings?

Tishkoff: Sure, well, humans are unique in their ability to digest milk as adults,

Tishkoff: because in most mammals the enzyme called lactase,

Tishkoff: which is expressed in the small intestine, is shut down after weaning,

Tishkoff: so in humans at around age 2 to 6 years old.

Tishkoff: And in individuals who can digest milk as adults,

Tishkoff: this enzyme is kept active and it plays a role in metabolizing the sugar

Tishkoff: present in milk, called lactose.

Tishkoff: So the majority of humans cannot digest milk;

Tishkoff: however, in populations whose ancestors have historically practiced dairying

Tishkoff: or domesticating cattle, pastoralists,

Tishkoff: they have adapted the ability to digest milk as adults.

Tishkoff: So those individuals who can digest milk are referred to as lactose tolerant.

Tishkoff: And lactose tolerance is most common in northern European populations

Tishkoff: such as the Finnish population, less common in Mediterranean populations,

Tishkoff: and very uncommon in East Asians, Amerindians and West Africans.

Tishkoff: However, in East African pastoralists who have domesticated cattle,

Tishkoff: they have evolved the ability to digest milk as adults,

Tishkoff: and it appears that they have done so independently of Europeans.

Machalek: Can you tell me the role that computers play in your research?

Tishkoff: Well, computers play a critical role

Tishkoff: because what we do is we study variation in modern populations

Tishkoff: and we have to make inferences about past events.

Tishkoff: And one of the ways that we do this is by computer simulation.

Tishkoff: So for example, we can simulate a scenario in which this adaptive mutation

Tishkoff: that allowed people to digest milk as adults arose some number of years ago,

Tishkoff: and by looking at the pattern of variation in modern populations,

Tishkoff: we can try to use computer simulation to infer

Tishkoff: how old that mutation is, for example,

Tishkoff: and we can also infer how strong the selective force must have been

Tishkoff: to make it reach the frequency that we observe it at in modern populations.

Tishkoff: We estimate the mutation, the most common mutation,

Tishkoff: that we found in East Africa, to be roughly 3,00:0 to 7,00:0 years old,

Tishkoff: and we estimated the mutation in Europeans to be roughly 7,00:0 to 9,00:0 years old.

Tishkoff: That was interesting because archeological data suggest

Tishkoff: that the origins of pastoralism were either in North Africa

Tishkoff: or the Middle East roughly 7,00:0 to 9,00:0 years ago,

Tishkoff: but cattle were not introduced south of the Sahara

Tishkoff: due to arid conditions until roughly 5,00:0 years ago,

Tishkoff: and then they were introduced more recently

Tishkoff: into southern Kenya and Tanzania around 3,00:0 years ago.

Tishkoff: So it fits strikingly well with our estimates for the age of this mutation.

Tishkoff: The mutation had to have occurred.

Tishkoff: And simultaneously or coincidentally, in that population,

Tishkoff: they had developed a new technology, which was domesticating cattle.

Tishkoff: Those individuals who by chance had

Tishkoff: that mutation were better able to digest milk as adults.

Tishkoff: And this gave them a selective advantage.

Tishkoff: They were able to have more children,

Tishkoff: and their children had more children, and so on,

Tishkoff: and so it rapidly rose in the population,

Tishkoff: together with the practice of pastoralism.

Machalek: Dr. Tishkoff,

Machalek: I know that you have taken a number of trips to Africa over the past 10 years.

Machalek: Can you tell us about some of the adventures that you had in Africa?

Tishkoff: Sure, we had many adventures.

Tishkoff: When we first started doing this research, I had never done field work before

Tishkoff: and I was not certain of things such as where am I going to sleep,

Tishkoff: how am I going to get to these remote villages,

Tishkoff: how am I going to process the blood to isolate the DNA in regions

Tishkoff: where there is no electricity.

Tishkoff: And we came up with creative ways to deal with this.

Tishkoff: So we brought all of our own equipment.

Tishkoff: We brought our own sleeping bags. We brought our own tents

Tishkoff: or sometimes we stayed at guesthouses in villages.

Tishkoff: We brought a portable centrifuge and plugged that into the car battery

Tishkoff: so we could have our own little genetics lab anywhere

Tishkoff: in Africa no matter how remote the region.

Tishkoff: So one of the wonderful things of working in that region is interacting

Tishkoff: with the local people and learning about these fascinating cultures

Tishkoff: and working with different tribes such as the Masai, for example,

Tishkoff: but it also can be at times somewhat dangerous depending on the region that you go to.

Tishkoff: But again, I think the key to success is involving local people

Tishkoff: in the research and having local participants.

Tishkoff: And as long as the people that we're studying are included in the research,

Tishkoff: we generally had no problems at all.

Machalek: Thank you Dr. Tishkoff.

Machalek: Best wishes on your research and happy trails on your next trip to Africa.