Communicated by Motoo Kimura, National Institute of Genetics, Shizuoka-ken, Japan, September 9, 1994 ABSTRACT We analyzed the complete mitochondrial DNA (mtDNA) sequences of three humans (African, European, and Japanese), three African apes (common and pygmy chimpanzees, and gorilla), and one orangutan in an attempt to estimate most accurately the substitution rates and divergence times of hominoid mtDNAs. Nonsynonymous substitutions and substitutions in RNA genes have accumulated with an approximately clock-like regularity. From these substitutions and under the assumption that the orangutan and African apes diverged 13 million years ago, we obtained a divergence time for humans and chimpanzees of 4.9 million years. This divergence time permitted calibration of the synonymous substitution rate (3.89 x 10-8/site per year). To obtain the substitution rate in the displacement (D)-loop region, we compared the three human mtDNAs and measured the relative abundance of substitutions in the D-loop region and at synonymous sites. The estimated substitution rate in the D-loop region was 7.00 x 10-8/site per year. Using both synonymous and D-loop substitutions, we inferred the age of the last common ancestor of the human mtDNAs as 143,000 ± 18,000 years. The shallow ancestry of human mtDNAs, together with the observation that the African sequence is the most diverged among humans, strongly supports the recent African origin of modern humans, Homo sapiens sapiens.Light will be thrown on the origin of man and his history (1).

Molecular biology has resurrected C. Darwin and T.H. Huxley's question about the origin of humans, but the precise branching pattern and dating remain controversial. To settle this issue, a large amount of sequence information is required. We determined mitochondrial (mt) DNA sequences for five hominoids; pygmy and common chimpanzees, gorilla, orangutan, and siamang. The common region compared with the known human sequence is 4759 bp long, encompassing genes for 11 transfer RNAs and 6 proteins. Because of the high substitution rates in mammalian mtDNA and an unprecedentedly large region compared, the sequence differences clearly indicate that the closest relatives to human are chimpanzees rather than gorilla. For dating the divergences of human, chimpanzee, and gorilla, we used only unsaturated parts of sequence differences in which the mtDNA genealogy is not obscured by multiple substitutions. The result suggests that gorilla branched off 7.7 +/- 0.7 million years (Myr) ago and human 4.7 +/- 0.5 Myr ago; the time difference between these divergences being as long as 3 Myr.

It has previously been shown that paternal mitochondrial DNA (mtDNA) can be detected in later generations in Drosophila. To further analyze the paternal transmission of mtDNA, the progeny of two intraspecific and three interspecific crosses were examined in the frequency of the paternal transmission of mtDNA, using closely related species of the melanogaster species subgroup. Types of mtDNA in the progeny of the individual backcrosses of F 1 females were analyzed by selective amplification of paternal mtDNA. More than 100 F 1 females were examined for each backcross. The same type of mtDNA as that of the paternal mtDNA was detected in approximately 20 -60% of the backcrosses. The present results indicate that paternal leakage occurs in the intraspecific crosses as well as in the interspecific crosses in Drosophila.

Presynaptic plasticity is known to modulate the strength of synaptic transmission. However, it remains unknown whether regulation in presynaptic neurons can evoke excitatory and inhibitory postsynaptic responses. We report here that the Caenorhabditis elegans homologs of MAST kinase, Stomatin, and Diacylglycerol kinase act in a thermosensory neuron to elicit in its postsynaptic neuron an excitatory or inhibitory response that correlates with the valence of thermal stimuli. By monitoring neural activity of the valence-coding interneuron in freely behaving animals, we show that the alteration between excitatory and inhibitory responses of the interneuron is mediated by controlling the balance of two opposing signals released from the presynaptic neuron. These alternative transmissions further generate opposing behavioral outputs necessary for the navigation on thermal gradients. Our findings suggest that valence-encoding interneuronal activity is determined by a presynaptic mechanism whereby MAST kinase, Stomatin, and Diacylglycerol kinase influence presynaptic outputs.

We have described a novel gene transfer system, in which subcutaneously into mice every 4 weeks. These mice were replication-incompetent, T antigen-deleted simian virus-40 bled every 2 weeks and their sera assayed for antibody (SV40) is used as the transduction vehicle. We report here activity against HBsAg and SV40. Production of anti-HBs successful immunization using such an SV40-derived viral was measured by ELISA and confirmed by Western blot vector. Hepatitis B surface antigen (HBsAg) cDNA was analysis, both of which demonstrated significant levels of cloned downstream of two tandem SV40 early promoters anti-HBs after the second injection. We also tested proto yield a T antigen-deficient SV40 derivative, SV(HBS).duction of anti-SV40 antibodies by the ability of sera to Cultured TC7 cells were exposed to SV(HBS), and neutralize SV(HBS) infectivity. We found no evidence of expression of HBsAg was detected 24 h later by Northern neutralization of SV(HBS) infectivity even after eight inocublot and RT-PCR analysis. Immunochemistry and Western lations. Thus, replication-incompetent SV40 is itself not a blot analysis were also performed 24 h after infection to strong antigen. Our data suggest that SV40-based transdetect expression of HBsAg. Once it was ascertained that duction systems may be a useful vehicle for immunization we could express HBsAg in this way, we used SV(HBS) to and for other gene transfer applications when a need for elicit anti-HBs. SV(HBS) was injected intraperitoneally or multiple inoculations is anticipated.