HUMAN EVOLUTION AND MOLECULAR BIOLOGY JEROLD M. LOWENSTEIN* and ADRIENNE L. ZIHLMANf The molecular biology revolution is having a profound impact on medical and biological progress and has also changed the rules of the game in the study ofhuman evolution. Under the old rules, the primate evolutionary tree was deduced from anatomical similarities between living and fossil primates, including man, and genetic relationships were likewise deduced from these anatomical resemblances. Thus, from the time of Darwin it has been recognized that among all living primates modern man is anatomically most like the African apes, the chimpanzee and gorilla. During the past 2 decades the prevailing interpretation of the fossil record, believed to contain "manlike" apes 14 million years old, indicated that the human lineage had separated from that ofthe apes at least 20 million years ago. During these same 2 decades, mounting evidence from immunological and molecular biological studies of living primates strongly contradicted this "early-divergence" hypothesis and suggested instead that man and the African apes diverged from a common ancestor a mere 5 million years ago. Evolution and Mohcular Biology The most direct evidence for the genetic similarity between two or more species derives from comparing their genetic material, the DNA. Additional evidence comes from comparisons of RNA, of protein amino acid sequences, of protein immunology, and of karyotypes and chromosomal banding patterns. AU these kinds of comparisons have been made, and all have shown remarkable and equal genetic similarity among man, chimpanzee, and gorilla. The DNAs of the three species, from DNA hybridization experiments, are 99 percent identical [I]. ?Clinical professor of medicine, University of California, San Francisco, California 94143. tProfessor of anthropology, University of California, Santa Cruz, California 95064.© 1984 by The University of Chicago. All rights reserved. 0031-5982/84/2704-0406$01.00 Perspectives in Biology and Medicine, 27, 4 · Summer 1984 | 61 1 TRADITIONAL PHYLOGENY ?+* '*» Human Chimpanzee Gorilla Orangutan Gibbon MOLECULAR PHYLOGENY Human Chimpanzee Gorilla Orangutan Gibbon 30 25 20 15 10 Million Years Ago Fig. 1.—Comparison of the traditional phylogeny of hominoid evolution with that derived from molecular data. The traditional view was strongly influenced by the conviction that Ramapithecus (R), a fossil genus dated as old as 14 million years ago, was on the human lineage. This opinion was based on teeth that resembled those of humans in some but not all respects. Recent discoveries ??Ramapithecus face and limb bones have been interpreted as showing closer relations to the orangutan. Australopithecus (A), with fossils going back almost 4 million years, is the oldest undisputed hominid. In contrast with the traditional phylogeny, the molecular one places Ramapithecus somewhere on the lineage ancestral or parallel to that of all living hominoids and has Australopithecus near the divergence of the human line from that of the African apes. When these data first emerged, they were surprising in two respects: first, in the degree of genetic similarity between humans and African apes; second, in that chimpanzee and gorilla are genetically no more similar to each other than either is to humans—anatomically, of course, the two apes are much more like each other than they are like us. These findings carry two logical implications: that morphological and genetic changes have occurred at different rates in these three lineages, and that the man-ape evolutionary divergence was much more recent than the 15—20 million years previously thought (fig. 1). Ifit is assumed that primate DNA has evolved at more or less the same rate as that of other animals whose divergence times can be inferred from the fossil record, then humans, chimpanzees, and gorillas had a 612 J Jerold M. Lowenstein and Adrienne L. Zihlman ¦ Human Evolution common ancestor, presumably in Africa, about 5 million years ago. The "molecular clock" ofDNA base-pair and amino acid sequence changes in animals descended from a common ancestor provides a badly needed quantitative control on estimates formerly based on morphological differences . For example, two different paleontologists, using anatomical characteristics, estimated the chimpanzee-gorilla divergence times at 3 million years [2] and 15 million years [3] ago. molecular clock Historically, immunological techniques led the way in demonstrating evolutionary relationships based on molecular rather than gross anatomical similarities. Around...