Fossils and molecular data are two independent sources of information that should in principle provide consistent inferences of when evolutionary lineages diverged. Here we use an alternative approach to genetic inference of species split times in recent human and ape evolution that is independent of the fossil record. We first use genetic parentage information on a large number of wild chimpanzees and mountain gorillas to directly infer their average generation times. We then compare these generation time estimates with those of humans and apply recent estimates of the human mutation rate per generation to derive estimates of split times of great apes and humans that are independent of fossil calibration. We date the human-chimpanzee split to at least 7-8 million years and the population split between Neanderthals and modern humans to 400,000-800,000 y ago. This suggests that molecular divergence dates may not be in conflict with the attribution of 6-to 7-million-y-old fossils to the human lineage and 400,000-yold fossils to the Neanderthal lineage.hominin | molecular dating | primate | speciation O ver 40 y ago, Sarich and Wilson used immunological data to propose that humans and African great apes diverged only about 5 million y ago, some three to four times more recently than had been assumed on the basis of the fossil record (1). Although contentious at the time (e.g., ref. 2), this divergence has since been repeatedly estimated from DNA sequence data at 4-6 million years ago (Ma) (3-8). However, this estimate is incompatible with the attribution of fossils older than 6 Ma to the human lineage. Although the assignment of fossils such as the ∼6 Ma Orrorin (9) and the 6-7 Ma Sahelanthropus (10) to the human lineage remains controversial (11), it is also possible that the divergence dates inferred from DNA sequence data are too recent.The total amount of sequence differences observed today between two evolutionary lineages can be expressed as the sum of two values: the sequence differences that accumulated since gene flow ceased between the lineages ("split time") and the sequence differences that correspond to the diversity in the common ancestor of both lineages. The extent of variation in the ancestral species may be estimated from the variance of DNA sequence differences observed across different parts of the genome between the species today, which will be larger the greater the level of variation in the ancestral population. By subtracting this value from the total amount of sequence differences, the sequence differences accumulated since the split can be estimated. The rate at which DNA sequence differences accumulate in the genome ("mutation rate") is needed to then convert DNA sequence differences into split times.In prior research, mutation rates have been calculated using species split times estimated from the fossil record as calibration points. For calculating split times between present-day humans and great apes, calibration points that assume DNA sequence differences between humans and orangutans...

We tested whether the cultural background of raters influenced ratings of chimpanzee personality. Our study involved comparing personality and subjective well-being ratings of 146 chimpanzees in Japan that were housed in zoos, research institutes, and a retirement sanctuary to ratings of chimpanzees in US and Australian zoos. Personality ratings were made on a translated and expanded version of a questionnaire used to rate chimpanzees in the US and Australia. Subjective well-being ratings were made on a translated version of a questionnaire used to rate chimpanzees in the US and Australia. The mean interrater reliabilities of the 43 original adjectives did not markedly differ between the present sample and the original sample of 100 zoo chimpanzees in the US. Interrater reliabilities of these samples were highly correlated, suggesting that their rank order was preserved. Comparison of the factor structures for the Japanese sample and for the original sample of chimpanzees in US zoos indicated that the overall structure was replicated and that the Dominance, Extraversion, Conscientiousness, and Agreeableness domains clearly generalized. Consistent with earlier studies, older chimpanzees had higher Dominance and lower Extraversion and Openness scores. Correlations between the six domain scores and subjective well-being were comparable to those for chimpanzees housed in the US and Australia. These findings suggest that chimpanzee personality ratings are not affected by the culture of the raters.

We have recently isolated a novel cytomatrix at the active zone (CAZ)–associated protein, CAST, and found it directly binds another CAZ protein RIM1 and indirectly binds Munc13-1 through RIM1; RIM1 and Munc13-1 directly bind to each other and are implicated in priming of synaptic vesicles. Here, we show that all the CAZ proteins thus far known form a large molecular complex in the brain, including CAST, RIM1, Munc13-1, Bassoon, and Piccolo. RIM1 and Bassoon directly bind to the COOH terminus and central region of CAST, respectively, forming a ternary complex. Piccolo, which is structurally related to Bassoon, also binds to the Bassoon-binding region of CAST. Moreover, the microinjected RIM1- or Bassoon-binding region of CAST impairs synaptic transmission in cultured superior cervical ganglion neurons. Furthermore, the CAST-binding domain of RIM1 or Bassoon also impairs synaptic transmission in the cultured neurons. These results indicate that CAST serves as a key component of the CAZ structure and is involved in neurotransmitter release by binding these CAZ proteins.

The cytomatrix at the active zone (CAZ) has been implicated in defining the site of Ca2+-dependent exocytosis of neurotransmitter. We have identified here a novel CAZ protein of ∼120 kD from rat brain and named it CAST (CAZ-associated structural protein). CAST had no transmembrane segment, but had four coiled-coil domains and a putative COOH-terminal consensus motif for binding to PDZ domains. CAST was localized at the CAZ of conventional synapses of mouse brain. CAST bound directly RIM1 and indirectly Munc13-1, presumably through RIM1, forming a ternary complex. RIM1 and Munc13-1 are CAZ proteins implicated in Ca2+-dependent exocytosis of neurotansmitters. Bassoon, another CAZ protein, was also associated with this ternary complex. These results suggest that a network of protein–protein interactions among the CAZ proteins exists at the CAZ. At the early stages of synapse formation, CAST was expressed and partly colocalized with bassoon in the axon shaft and the growth cone. The vesicles immunoisolated by antibassoon antibody–coupled beads contained not only bassoon but also CAST and RIM1. These results suggest that these CAZ proteins are at least partly transported on the same vesicles during synapse formation.

Over the past several years, acute and fatal respiratory illnesses have occurred in the habituated group of wild chimpanzees at the Mahale Mountains National Park, Tanzania. Common respiratory viruses, such as measles and influenza, have been considered possible causative agents; however, neither of these viruses had been detected. During the fatal respiratory illnesses in 2003, 2005 and 2006, regular observations on affected individuals were recorded. Cause-specific morbidity rates were 98.3, 52.4 and 33.8%, respectively. Mortality rates were 6.9, 3.2 and 4.6%; all deaths were observed in infants 2 months-2 years 9 months of age. Nine other chimpanzees have not been seen since the 2006 outbreak and are presumed dead; hence, morbidity and mortality rates for 2006 may be as high as 47.7 and 18.5%, respectively. During the 2005 and 2006 outbreaks, 12 fecal samples were collected from affected and nonaffected chimpanzees and analyzed for causative agents. Analysis of fecal samples from 2005 suggests the presence of paramyxovirus, and in 2006 a human-related metapneumovirus was detected and identified in an affected chimpanzee whose infant died during the outbreak. Our findings provide preliminary evidence that the causative agent associated with these illnesses is viral and contagious, possibly of human origin; and that, possibly more than one agent may be circulating in the population. We recommend that baseline health data be acquired and food wadge and fecal samples be obtained and bio-banked as early as possible when attempting to habituate new groups of chimpanzees or other great apes. For already habituated populations, disease prevention strategies, ongoing health monitoring programs and reports of diagnostic findings should be an integral part of managing these populations. In addition, descriptive epidemiology should be a major component of disease outbreak investigations.

No abstract

Nectins are Ca2+-independent immunoglobulin-like cell-cell-adhesion molecules consisting of four members. Nectins homophilically and heterophilically trans-interact to form a variety of cell-cell junctions, including cadherin-based adherens junctions in epithelial cells and fibroblasts in culture, synaptic junctions in neurons, and Sertoli cell-spermatid junctions in the testis, in cooperation with, or independently of, cadherins. To further explore the function of nectins, we generated nectin 1–/– and nectin 3–/– mice. Both nectin 1–/– and nectin 3–/– mice showed a virtually identical ocular phenotype, microphthalmia, accompanied by a separation of the apex-apex contact between the pigment and non-pigment cell layers of the ciliary epithelia. Immunofluorescence and immunoelectron microscopy revealed that nectin 1 and nectin 3, but not nectin 2, localized at the apex-apex junctions between the pigment and non-pigment cell layers of the ciliary epithelia. However, nectin 1–/– and nectin 3–/– mice showed no impairment of the apicolateral junctions between the pigment epithelia where nectin 1, nectin 2 and nectin 3 localized, or of the apicolateral junctions between the non-pigment epithelia where nectin 2 and nectin 3, but not nectin 1, localized. These results indicate that the heterophilic trans-interaction between nectin 1 and nectin 3 plays a sentinel role in establishing the apex-apex adhesion between the pigment and non-pigment cell layers of the ciliary epithelia that is essential for the morphogenesis of the ciliary body.

A serine/threonine kinase SAD-1 in C. elegans regulates synapse development. We report here the isolation and characterization of mammalian orthologs of SAD-1, named SAD-A and SAD-B, which are specifically expressed in the brain. SAD-B is associated with synaptic vesicles and, like the active zone proteins CAST and Bassoon, is tightly associated with the presynaptic cytomatrix in nerve terminals. A short conserved region (SCR) in the COOH-terminus is required for the synaptic localization of SAD-B. Overexpression of SAD-B in cultured rat hippocampal neurons significantly increases the frequency of miniature excitatory postsynaptic current but not its amplitude. Introduction of SCR into presynaptic superior cervical ganglion neurons in culture significantly inhibits evoked synaptic transmission. Moreover, SCR decreases the size of the readily releasable pool measured by applying hypertonic sucrose. Furthermore, SAD-B phosphorylates the active zone protein RIM1 but not Munc13-1. These results suggest that mammalian SAD kinase presynaptically regulates neurotransmitter release.