Over time, cryo-EM images of this lactase protein HUMAN GENETICS have sharpened from blobs (left) to filigrees (right). images. In work from 1975 to 1986, Frank How Africans evolved a came up with a way to make sense of the data, by using algorithms to sort the images into related groups and then averaging each palette of skin tones one. This not only sharpened the 2D im- ages, but also allowed them to be combined Gene variants show that the evolution of skin color into a 3D structure. was anything but black and white In the early 1980s, Dubochet sharpened the resolution further by freezing the sam- ples, locking the biomolecules into place. By Ann Gibbons of UV radiation. Then, when humans mi- Freezing biological samples ordinarily pro- grated out of Africa and headed to the far duces ice crystals, which diffract the electron ost people associate Africans with north, they evolved lighter skin as an adap- beam and blur the image. Dubochet realized . But different groups of tation to limited sunlight. (Pale skin synthe- that if the water was frozen quickly enough— people in Africa have almost ev- sizes more vitamin D when light is scarce; vitrified, like glass—ice crystals wouldn’t ery skin color on the planet, from Science, 21 November 2014, p. 934.) form. By cooling samples with liquid nitro- deepest black in the Dinka of South Previous research on skin-color genes fit gen to –196°C, Dubochet created breathtak- to beige in the San of South that picture. For example, a “depigmenta- Downloaded from ingly sharp images. Because the molecules MAfrica. Now, researchers have discovered a tion gene” called SLC24A5 linked to pale are flash-frozen in a variety of states, re- handful of new gene vari- skin swept through Euro- searchers can assemble these pictures into ants responsible for this pean populations in the movies that reveal how the shape of the palette of tones. past 6000 years. protein changes as it does its work in the cell. The study, published on- But Tishkoff’s team These advances brought the reso- line this week in Science, found that the story of lution of cryo-EM to 0.5 nanometers. traces the evolution of skin color evolution isn’t http://science.sciencemag.org/ That still couldn’t match x-ray crystallo- these genes and how they so black and white. Her graphy, which today achieves a resolution of traveled around the world. team, including Afri- 0.2 nanometers or better. “We kind of got While the dark skin of can researchers, used a stuck,” Frank says. But Henderson pushed some Pacific Islanders can light meter to measure to replace film-based detectors with digital be traced to Africa, gene skin reflectance in 2092 ones, and today’s cryo-EM machines can get variants from Eurasia also people in , Tan- 0.25-nanometer resolution. “That brought seem to have made their zania, and . us into the realm of x-ray crystallography,” way back to Africa. And They found the darkest Frank says. surprisingly, some of the skin in the Nilo-Saharan

Cryo-EM techniques are revealing the mutations responsible for pastoralist populations on January 9, 2018 structures of ever-larger complexes includ- lighter skin in Europeans of eastern Africa, such as ing the ribosome, the cellular factory that turn out to have an ancient the Mursi and Surma, and produces proteins, and the spliceosome, African origin. the lightest skin in the the complex that trims noncoding material “This is really a land- San of southern Africa, out of RNA. Within reach is a vast world mark study of skin color as well as many shades in of membrane-bound proteins and protein diversity,” says geneti- between, as in the Agaw complexes that can’t be crystallized, Hen- cist Greg Barsh of the people of Ethiopia. derson says. “In a few years, perhaps 5 years, HudsonAlpha Institute At the same time, they we might know most of the structures, at for Biotechnology in collected blood samples least in humans and pathogenic bacteria,” Huntsville, Alabama. for genetic studies. They he says. “It’s really quite an exciting time.” Researchers agree that sequenced more than The U.S. National Institutes of Health our early australopith- 4 million single nucleo- and other funding agencies are spending ecine ancestors in Africa tide polymorphisms tens of millions of dollars to build new probably had light skin Researchers have identified genes that (SNPs)—places where a cryo-EM centers to expand access to the beneath hairy pelts. “If help create diverse skin tones, such single letter of the ge- machines. One upshot, Ramakrishnan says, you shave a chimpanzee, as those seen in the Agaw (top) and netic code varies across is that structural biologists like himself are its skin is light,” says evo- Surma (bottom) peoples of Africa. the genomes of 1570 of getting out of the business of x-ray crystal- lutionary geneticist Sarah these Africans. They lography. “Nobody in my lab wanted to set Tishkoff of the University of Pennsylvania, found four key areas of the genome where up crystallization trays anymore,” he says. the lead author of the new study. “If you specific SNPs correlate with skin color. The exodus could have an impact on the have body hair, you don’t need dark skin to The first surprise was that SLC24A5, billion-dollar, stadium-sized synchrotrons protect you from ultraviolet [UV] radiation.” which swept Europe, is also common in East that generate the x-ray light for crystallog- Until recently, researchers assumed that Africa—found in as many as half the mem- raphy experiments. If structural biologists after human ancestors shed most body hair, bers of some Ethiopian groups. This variant turn en masse to cryo-EM, “there might sometime before 2 million years ago, they arose 30,000 years ago and was probably soon be too many synchrotrons around,” quickly evolved dark skin for protection brought to eastern Africa by people migrat- j PHOTOS: ALESSIA RANCIARO AND SIMON R. THOMPSON ANDSIMON R. RANCIARO ALESSIA PHOTOS: Stark says. “That could happen.” from skin cancer and other harmful effects ing from the Middle East, Tishkoff says.

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But though many East Africans have this Manatees and the gene, they don’t have white skin, probably seagrass they graze on because it is just one of several genes that brought innovations from shape their skin color. the land back to the sea. The team also found variants of two neighboring genes, HERC2 and OCA2, which are associated with light skin, eyes, and hair in Europeans but arose in Africa; these variants are ancient and common in the light-skinned . The team proposes that the variants arose in Africa as early as 1 million years ago and spread later to Europeans and Asians. “Many of the gene variants that cause light skin in Eu- PALEONTOLOGY rope have origins in Africa,” Tishkoff says. The most dramatic discovery concerned a gene known as MFSD12. Two mutations Evolution accelerated when that decrease expression of this gene were found in high frequencies in people with the darkest skin. These variants arose life set foot on land Downloaded from about a half-million years ago, suggest- ing that human ancestors before that time Opportunities of terrestrial living sped innovation may have had moderately dark skin, rather than the deep black hue created today by By Elizabeth Pennisi a biochemist at University College these mutations. . For example, seagrasses brought These same two variants are found in Mel- ife probably originated in water, but land plants’ systems for transporting water anesians, Australian Aborigines, and some nature did some of its best work once and acquiring nutrients back to the marine http://science.sciencemag.org/ Indians. These people may have inherited organisms made landfall. That’s what environment. Vermeij found two other traits the variants from ancient migrants from Geerat Vermeij has concluded after that are still restricted to land. Another, the Africa who followed a “southern route” out surveying fossils and family trees to tendency of animals to guard their plant or of East Africa, along the southern coast of discover where and when some of plantlike food sources—appeared about 50 to Melanesia and , Tishkoff Llife’s greatest modern advances evolved. million years ago in both places. Just one, says. That idea, however, counters three ge- Almost all of these seemingly out-of-the- the ability to use electrical currents for netic studies that concluded last year that blue innovations, from fungus farming by communication and hunting—think electric Australians, Melanesians, and Eurasians insects to the water transport systems that eels—happened first, and only, in water. all descend from a single migration out of made tall trees possible, came about after Lalonde, too, has found evidence of differ-

Africa. Alternatively, this great migration plants and animals learned how to sur- ences in evolution on land and in the sea by on January 9, 2018 may have included people carrying variants vive on land some 440 million years ago, studying land-based and sea-going microbes for both light and dark skin, but the dark Vermeij, an evolutionary biologist at the that produced oxygen billions of years ago. variants later were lost in Eurasians. University of California, Davis, reported last But he and some others are not convinced To understand how the MFSD12 muta- week in Current Biology. that Vermeij has found a real pattern. “A ma- tions help make darker skin, the research- “The idea that a dramatic ‘pivot’ in the jor difficulty is avoiding bias in the selection ers reduced expression of the gene in locus and tempo of biological innovation of the set of major innovations,” Lalonde says. cultured cells, mimicking the action of the occurred once complex life colonized the Many innovations, such as long-distance mi- variants in dark-skinned people. The cells land surface is quite profound,” says Stefan gration and color vision, don’t show up in produced more eumelanin, the pigment Lalonde, a geobiologist at the European Insti- the fossil record and so were not counted. responsible for black and brown skin, hair, tute for Marine Studies in Plouzané, France. Still, the work “will encourage us to and eyes. The mutations may also change Many researchers have focused on how think about whether there is something skin color by blocking yellow pigments: newly land-based organisms coped with special about the terrestrial environment,” When the researchers knocked out MFSD12 gravity and the threat of desiccation. But says Charles Delwiche, an evolutionary in zebrafish and mice, red and yellow pig- Vermeij wondered instead how the move to biologist at the University of Maryland in ments were lost, and the mice’s light brown land might have changed the pace of evolu- College Park. Vermeij thinks life on land was coats turned gray. “This new mechanism tion. He compiled a list of key innovations less constrained because air is easier to move for producing intensely dark pigmentation that showed up in several groups of organ- around in than water, but Charles Wellman, OTO

is really the big story,” says Nina Jablonski, isms and provided a big competitive edge, a paleontologist at the University of Sheffield H P K

an anthropologist at Pennsylvania State such as herbivory by vertebrates, flight, in the , wonders whether the C

University in State College. echolocation, and warm-bloodedness. Exist- terrestrial environment was more stressful, S T O Y M A

The study adds to established research ing fossil evidence enabled him to date the forcing organisms to innovate to survive. And L A /

undercutting old notions of race. You can’t origin of a dozen of these adaptations. Delwiche suggests that the availability of new S OTO

use skin color to classify humans, any more Nine appeared first on land and later places to live was what fueled the surge of in- H P A

than you can use other complex traits like in the sea, he reported. “Once they novation following the conquest of the land. R O R

height, Tishkoff says. “There is so much evolved on land, they could re-enter the “I don’t know if I believe” the article, U A

diversity in Africans that there is no such oceans,” where they had a big effect on the Delwiche says. “But the thing that I love : O TO

j j H thing as an African race.” ecosystems there, comments Nick Lane, about it is it gets me thinking.” P

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