Accurately dating when the first bilaterally symmetrical animals arose is crucial to our understanding of early animal evolution. The earliest unequivocally bilaterian fossils are Ϸ555 million years old. In contrast, molecular-clock analyses calibrated by using the fossil record of vertebrates estimate that vertebrates split from dipterans (Drosophila) Ϸ900 million years ago (Ma). Nonetheless, comparative genomic analyses suggest that a significant rate difference exists between vertebrates and dipterans, because the percentage difference between the genomes of mosquito and fly is greater than between fish and mouse, even though the vertebrate divergence is almost twice that of the dipteran. Here we show that the dipteran rate of molecular evolution is similar to other invertebrate taxa (echinoderms and bivalve molluscs) but not to vertebrates, which significantly decreased their rate of molecular evolution with respect to invertebrates. Using a data set consisting of the concatenation of seven different amino acid sequences from 23 ingroup taxa (giving a total of 11 different invertebrate calibration points scattered throughout the bilaterian tree and across the Phanerozoic), we estimate that the last common ancestor of bilaterians arose somewhere between 573 and 656 Ma, depending on the value assigned to the parameter scaling molecular substitution rate heterogeneity. These results are in accord with the known fossil record and support the view that the Cambrian explosion reflects, in part, the diversification of bilaterian phyla.A lthough the Cambrian explosion is of singular importance to our understanding of the history of life, it continues to defy explanation (1). This defiance stems, in part, from our inability to distinguish between two competing hypotheses: whether the Cambrian explosion reflects the rapid appearance of fossils with animals having a deep but cryptic precambrian history, or whether it reflects the true sudden appearance and diversification of animals in the Cambrian (2). Because each hypothesis makes a specific prediction of when animals arose in time, one way to distinguish between these two hypotheses is to date animal diversifications by using a molecular clock (2). A number of previous clock studies (reviewed in refs. 3 and 4) have suggested that the last common ancestor of bilaterians (LCB) lived well over one billion years ago (5, 6), whereas others suggest that LCB arose Ϸ900 million years ago (Ma) (e.g., refs. 7-10), and still others are more consistent with an origination closer to the Cambrian (11-13). These deep estimates for the origin of LCB raise the question of how hundreds of millions of years of bilaterian evolution can escape detection, given that LCB and its near relatives should have had the capability of leaving both body and trace fossils (14-16).Because molecular clocks have several inherent problems, including how the clock is calibrated, how molecular substitution rates are estimated, and how heterogeneity in these rates is detected and corrected (3, 4), as well...

The current system for the ethical oversight of clinical research suffers from structural, procedural, and performance assessment problems. Initially conceived primarily to handle local investigator-initiated single-site studies, the system of institutionally-based committee review has become progressively more inefficient given the increased prevalence of commercially or federally sponsored multi-center trials. To date, proposed solutions do not adequately address these problems. Beginning with a review of these structural, procedural, and performance assessment problems, this article will then consider two proposals for addressing these deficiencies: (a) regional ethics organizations; and (b) IRBNet, a newly developed web-based program for cooperative IRB review. The strengths and weaknesses of these two approaches will be evaluated in light of recent experience with centralized review. The proposal to establish a system of regional ethics organizations presents a comprehensive approach to many of the problems faced by the current system. However, IRBNet offers an immediate and feasible solution to many of the problems faced by the review of multi-site clinical studies.