WHAT DONT WE KNOW? E very generation of anthropologists these will help reveal the ancestral genotype at approach that has identified a handful sets out to explore what it is that key places on the primate tree. ing genes. For example, MCPHI an makes us human. Famed paleo- The genetic differences revealed between cause microcephaly when mutated, anthropologist Louis Leakey thought humans and chimps are likely to be profound, causes speech defects, and all three show signs tools made the man, and so when he uncov- despite the oft-repeated statistic that only of selection pressure during human, but not ered hominid bones near stone tools in Tan- about 1. 2%of our DNA differs from that of chimp, evolution. Thus they may have played zania in the 1960s, he labeled the putative chimps. A change in every 100th base could roles in the evolution of humans'large brains 2 toolmaker Homo habilis, the earliest member affect thousands of genes, and the percentage and speech. of the human genus. But then primatologist difference becomes much larger if you count But even with genes like these, it is often Jane Goodall demonstrated that chimps also insertions and deletions. Even if we document difficult to be completely sure of what they do use tools of a sort, and today researchers all of the perhaps 40 million sequence differ- Knockout experiments, the classic way to debate whether H habilis truly belongs in ences between humans and chimps, what do reveal function, can, t be done in humans and omo. Later studies have honed in on traits they mean? Many are probably simply the apes for ethical reasons. Much of the such as bipedality, culture, language, humor, consequence of 6 million years of genetic will therefore demand comparative analyses and, of course, a big brain as the unique drift, with little effect on body or behavior, of the genomes and phenotypes of large birthright of our species. Yet many of these whereas other small changes--perhaps in numbers of humans and apes. Already, some traits can also be found, at least to some regulatory, noncoding sequencesmay have researchers are pushing for a"great ape degree, in other creatures: Chimps have rudi- dramatic consequences tide of genomic data with more phenotypic N What Genetic that clues to function est be glea by mining natura Changes Made Us human variability, atching mutations in living people to Uniquely human o g mentary culture, parrots speak, and some rats Half of the differences might define a E seem to giggle when tickled. chimp rather than a human. How can we s What is beyond doubt is that humans, sort them all out? ce every other species, have a unique One way is to zero in on the genes that subtle differences in a genom by our evolutionary history. have been favored by natural selection in biology and behavior Now, for the first time, scientists can address humans. Studies seeking subtle signs of Both strategies face s anthropology's fundamental question at a selection in the DNA of humans and logistical and ethica E new level: What are the genetic changes that other primates have identified dozens of but some o03sS389=0= genes, in particular those involved in progress seems likely. i mate genome data beginning to pour in, we sensory systems such as olfaction and taste, human traits will, however, include more than 3 are entering an era in which it may become and more DNA Scientists may eventually circle back possible to pinpoint the genetic changes that But not all of these genes helped set us to those long-debated traits of sophisticated ef help separate us from our closest relatives. a apart from our ape cousins originally. Our language, culture, and technology, in which e been released, and a more detailed version is response to malaria, but malaria defense didn't We're in the age of the genome, but we can t expected soon. The genome of the macaque is make us human. So some researchers have still recognize that it takes much more than a nearly complete, the orangutan is under way, started with clinical mutations that impair key genes to make the human and the marmoset was recently approved. All traits, then traced the genes' evolution, an -ELIZABETH CULOTTA How much do vertebrates continued>> ow do system to fight infection? It's a driver of ar This system predates the verte- brate adaptive immune response Does immunologic memory Even if one accepts that prions are just Its relative importance is unclear, but immunol- seems to be yes, and ogists are working the question remain to find ou inkers, but experiments with hy and how and how do they kill cells once omething is not there, so the there, for example. question likely will not go away. www.sciencemag.orgScieNceVol3091jUlY2005
91 CREDITS (LEFT TO RIGHT): FRITZ POLKING/VISUALS UNLIMITED;TERRY HUSEBYE/GETTY IMAGES Special Section E very generation of anthropologists sets out to explore what it is that makes us human. Famed paleoanthropologist Louis Leakey thought tools made the man, and so when he uncovered hominid bones near stone tools in Tanzania in the 1960s, he labeled the putative toolmaker Homo habilis, the earliest member of the human genus. But then primatologist Jane Goodall demonstrated that chimps also use tools of a sort, and today researchers debate whether H. habilis truly belongs in Homo. Later studies have honed in on traits such as bipedality, culture, language, humor, and, of course, a big brain as the unique birthright of our species. Yet many of these traits can also be found, at least to some degree, in other creatures: Chimps have rudimentary culture, parrots speak, and some rats seem to giggle when tickled. What is beyond doubt is that humans, like every other species, have a unique genome shaped by our evolutionary history. Now, for the first time, scientists can address anthropology’s fundamental question at a new level: What are the genetic changes that make us human? With the human genome in hand and primate genome data beginning to pour in, we are entering an era in which it may become possible to pinpoint the genetic changes that help separate us from our closest relatives. A rough draft of the chimp sequence has already been released, and a more detailed version is expected soon. The genome of the macaque is nearly complete, the orangutan is under way, and the marmoset was recently approved. All these will help reveal the ancestral genotype at key places on the primate tree. The genetic differences revealed between humans and chimps are likely to be profound, despite the oft-repeated statistic that only about 1.2% of our DNA differs from that of chimps. A change in every 100th base could affect thousands of genes, and the percentage difference becomes much larger if you count insertions and deletions. Even if we document all of the perhaps 40 million sequence differences between humans and chimps, what do they mean? Many are probably simply the consequence of 6 million years of genetic drift, with little effect on body or behavior, whereas other small changes—perhaps in regulatory, noncoding sequences—may have dramatic consequences. Half of the differences might define a chimp rather than a human. How can we sort them all out? One way is to zero in on the genes that have been favored by natural selection in humans. Studies seeking subtle signs of selection in the DNA of humans and other primates have identified dozens of genes, in particular those involved in host-pathogen interactions, reproduction, sensory systems such as olfaction and taste, and more. But not all of these genes helped set us apart from our ape cousins originally. Our genomes reveal that we have evolved in response to malaria, but malaria defense didn’t make us human. So some researchers have started with clinical mutations that impair key traits, then traced the genes’ evolution, an approach that has identified a handful of tantalizing genes. For example, MCPH1 and ASPM cause microcephaly when mutated, FOXP2 causes speech defects, and all three show signs of selection pressure during human, but not chimp, evolution. Thus they may have played roles in the evolution of humans’ large brains and speech. But even with genes like these, it is often difficult to be completely sure of what they do. Knockout experiments, the classic way to reveal function, can’t be done in humans and apes for ethical reasons. Much of the work will therefore demand comparative analyses of the genomes and phenotypes of large numbers of humans and apes. Already, some researchers are pushing for a “great ape ‘phenome’ project” to match the incoming tide of genomic data with more phenotypic information on apes. Other researchers argue that clues to function can best be gleaned by mining natural human variability, matching mutations in living people to subtle differences in biology and behavior. Both strategies face logistical and ethical problems, but some progress seems likely. A complete understanding of uniquely human traits will, however, include more than DNA. Scientists may eventually circle back to those long-debated traits of sophisticated language, culture, and technology, in which nurture as well as nature plays a leading role. We’re in the age of the genome, but we can still recognize that it takes much more than genes to make the human. –ELIZABETH CULOTTA What Genetic Changes Made Us Uniquely Human continued >> W HAT D O N ’ T W E K NOW ? Is inflammation a major factor in all chronic diseases? It’s a driver of arthritis, but cancer and heart disease? More and more, the answer seems to be yes, and the question remains why and how. How do prion diseases work? Even if one accepts that prions are just misfolded proteins, many mysteries remain. How can they go from the gut to the brain, and how do they kill cells once there, for example. How much do vertebrates depend on the innate immune system to fight infection? This system predates the vertebrate adaptive immune response. Its relative importance is unclear, but immunologists are working to find out. Does immunologic memory require chronic exposure to antigens? Yes, say a few prominent thinkers, but experiments with mice now challenge the theory. Putting the debate to rest would require proving that something is not there, so the question likely will not go away. ART DAVIS/USDA JUPITER IMAGES www.sciencemag.org SCIENCE VOL 309 1 JULY 2005 Published byAAAS on November 7, 2010 www.sciencemag.org Downloaded from
