Watching evolution in real time

In 1831, the young Charles Darwin set off on the H.M.S. Beagle, a Royal Navy sloop bound for detailed surveys of South America. He took with him the first volume of the massive trilogy “Principles of Geology” by Scottish geologist Charles Lyell. (He had the other volumes sent later.)

It was important reading, since it impressed on the young naturalist that the physical world is in constant flux, and had been for ages.

In 1837, Darwin read “An Essay on the Principle of Population” by Thomas Robert Malthus — and another seed was planted: the idea that life is a struggle for resources, and that (somehow) the fittest survive.

The ideas of Lyell and Malthus were part of a tapestry of contemporary concepts woven around the notion of evolution. But it was Darwin who synthesized the ideas, conceived of natural selection, and introduced evolution to a wide public with the publication in 1859 of “On the Origin of Species.”

In 1871, Darwin came out with “The Descent of Man,” which applied the idea of natural selection to human evolution.

How do Darwin’s ideas fare in the 21st century?

Very well, thank you. That’s from anthropological biologist Pardis Sabeti, an assistant professor in Harvard’s Department of Organismic and Evolutionary Biology. Her research into the genomes of both humans and pathogens involves looking for genes that are undergoing natural selection.

She also works at Harvard’s Center for Systems Biology, where her interests include the evolution of infectious diseases, especially malaria and Lassa fever.

Sabeti, 33, is a former Rhodes Scholar with a D. Phil. from Oxford and an M.D. from Harvard Medical School (where she was only the third woman to graduate summa cum laude). She was named one of the top 100 living geniuses by Great Britain’s Daily Telegraph. In her spare time (what spare time?), the Iranian-born Sabeti is lead singer in the alternative rock band Thousand Days.

In a Feb. 26 lecture called “Evolution in the Post-Genomic Age,” Sabeti outlined the durable potency of Darwin’s ideas to a capacity crowd at the Geological Lecture Hall. It was one of a series at the Harvard Museum of Natural History in honor of the 200th year of Darwin’s birth.

Sabeti credited Malthus and Lyell for inspiring Darwin, then spun forward to 1948, the year British biologist J.B.S. Haldane speculated that a range of diverse red blood cell disorders in tropical areas, including sickle cell anemia, appeared to be adaptations to malaria.

Sabeti called the genetic reaction to malaria “one of the first examples of human adaptation,” and a rare proof of natural selection at work. “Within our lifetimes we’re seeing evolution in action.”

Malaria emerged as one “driver of human evolution,” she said. It showed that infectious disease could cause evolutionary pressure urgent enough to prompt rapid, protective change in humans.

Sabeti named other factors that might speed up human evolution. Climate change can alter temperature or relative sunlight. Changes in diet can affect human evolution, too, especially following the domestication of plants and animals.

In the 1990s, scientists started looking at another driver of human evolution: lactose tolerance, a response to milk from domesticated cows. This new “wide pool” of human nutrition, she said, followed the development of animal husbandry in Europe.

Adaptations to evolutionary pressures like malaria “leave distinct signals in the genome,” said Sabeti. Now that researchers have the tools to peer into the genome, “we see those signals all over,” she said. “The challenge is to elucidate what these things do.”

The human genome is like a giant book with 3 billion separate “letters” in it. But this big book fits into a cell nucleus smaller than a pinpoint — and nearly every human cell has a copy.

Within those 3 billion letters (that is, DNA base pairs), between 10 million and 20 million are polymorphic. In those places, human differences show up in the genome.

Those differences are the result of mutations that occur naturally. A new mutation that doesn’t affect survival will either disappear or take a very long time to establish itself in the areas of the genome humans hold in common.

But if a mutation enhances survival or reproductive success, said Sabeti, it will spread through a population very quickly, and become highly prevalent in a very short time.

“When we look through the genome,” she said, “we look for things that spread very quickly.” These changes will differ from what Sabeti called “ancestral states???? — the parts of the genome that humans had when they split from chimpanzees on the evolutionary tree around 6 million years ago.

But humans branched out from Africa only 75,000 years ago, dispersing throughout the rest of the world. That’s not much time in evolutionary terms, so humans still share a genome that is 99.9 percent identical.

Differences occur in response to differing human environments. Adaptations to malaria, for instance, are only prevalent in the tropics.

To look for genomic evolution in action, said Sabeti, “we look for places in the genome where there are strong differences.”

Some of the differences don’t seem to have explicit functionality. A mutation in the so-called EDAR gene, for example, is found in nearly all Chinese and Japanese. It gives them hair that’s twice as thick as that of Europeans.

But the EDAR gene itself controls the prenatal formation of hair, sweat glands, and teeth. It’s associated with “one of the most dramatic things associated with our evolution,” said Sabeti — shedding the full body hair that we had in the early post-chimp days.

Less hair means humans can dissipate heat faster, she said, making them — among other things — better endurance runners, an adaptation that meant more success hunting. (Our profuse sweating helps, too.)

“The vast majority of what we have found is completely novel,” said Sabeti. “We spend a lot of time hypothesizing,” including searches for candidate places on the genome that affect cell regulation and cancer.

“We’re inching our way along,” she said of the hunt for evolution and functionality in the genome. “We’re not that far along, but we have the tools now.”