ABSTRACT: To study the genomic divergences among hominoids and to estimate the effective population size of the common ancestor of humans and chimpanzees, we selected 53 autosomal intergenic nonrepetitive DNA segments from the human genome and sequenced them in a human, a chimpanzee, a gorilla, and an orangutan. The average sequence divergence was only 1.24% +/- 0.07% for the human-chimpanzee pair, 1.62% +/- 0.08% for the human-gorilla pair, and 1.63% +/- 0.08% for the chimpanzee-gorilla pair. These estimates, which were confirmed by additional data from GenBank, are substantially lower than previous ones, which included repetitive sequences and might have been based on less-accurate sequence data. The average sequence divergences between orangutans and humans, chimpanzees, and gorillas were 3.08% +/- 0.11%, 3.12% +/- 0.11%, and 3.09% +/- 0.11%, respectively, which also are substantially lower than previous estimates. The sequence divergences in other regions between hominoids were estimated from extensive data in GenBank and the literature, and Alus showed the highest divergence, followed in order by Y-linked noncoding regions, pseudogenes, autosomal intergenic regions, X-linked noncoding regions, synonymous sites, introns, and nonsynonymous sites. The neighbor-joining tree derived from the concatenated sequence of the 53 segments--24,234 bp in length--supports the Homo-Pan clade with a 100% bootstrap value. However, when each segment is analyzed separately, 22 of the 53 segments (approximately 42%) give a tree that is incongruent with the species tree, suggesting a large effective population size (N(e)) of the common ancestor of Homo and Pan. Indeed, a parsimony analysis of the 53 segments and 37 protein-coding genes leads to an estimate of N(e) = 52,000 to 96,000. As this estimate is 5 to 9 times larger than the long-term effective population size of humans (approximately 10,000) estimated from various genetic polymorphism data, the human lineage apparently had experienced a large reduction in effective population size after its separation from the chimpanzee lineage. Our analysis assumes a molecular clock, which is in fact supported by the sequence data used. Taking the orangutan speciation date as 12 to 16 million years ago, we obtain an estimate of 4.6 to 6.2 million years for the Homo-Pan divergence and an estimate of 6.2 to 8.4 million years for the gorilla speciation date, suggesting that the gorilla lineage branched off 1.6 to 2.2 million years earlier than did the human-chimpanzee divergence.
