Unresolved molecular phylogenies of gibbons and siamangs (Family: Hylobatidae) based on mitochondrial, Y-linked, and X-linked loci indicate a rapid Miocene radiation or sudden vicariance event.

According to recent taxonomic reclassification, the primate family Hylobatidae contains four genera (Hoolock, Nomascus, Symphalangus, and Hylobates) and between 14 and 18 species, making it by far the most species-rich group of extant hominoids. Known as the "small apes", these small arboreal primates are distributed throughout Southeast, South and East Asia. Considerable uncertainty surrounds the phylogeny of extant hylobatids, particularly the relationships among the genera and the species within the Hylobates genus. In this paper we use parsimony, likelihood, and Bayesian methods to analyze a dataset containing nearly 14 kilobase pairs, which includes newly collected sequences from X-linked, Y-linked, and mitochondrial loci together with data from previous mitochondrial studies. Parsimony, likelihood, and Bayesian analyses largely failed to find a significant difference among phylogenies with any of the four genera as the most basal taxon. All analyses, however, support a tree with Hylobates and Symphalangus as most closely related genera. One strongly supported phylogenetic result within the Hylobates genus is that Hylobates pileatus is the most basal taxon. Multiple analyses failed to find significant support for any singular genus-level phylogeny. While it is natural to suspect that there might not be sufficient data for phylogenetic resolution (whenever that situation occurs), an alternative hypothesis relating to the nature of gibbon speciation exists. This lack of resolution may be the result of a rapid radiation or a sudden vicariance event of the hylobatid genera, and it is likely that a similarly rapid radiation occurred within the Hylobates genus. Additional molecular and paleontological evidence are necessary to better test among these, and other, hypotheses of hylobatid evolution.

Tempo and mode of evolution in an orthologous Can SINE.

Tempo and mode of nucleotide change were examined in an orthologous carnivoran nuclear repetitive DNA element (Can SINE), and compared with those of the transthyretin intron I (TR-i-I) sequence in which it is embedded, by using a phylogenetic framework. The Can SINE is found in representatives of all living caniform carnivoran families, but no living feliform families. This suggests insertion 40-65 MYA, after the two lineages split, but before the caniform radiation. Despite linkage and a long shared evolutionary history, both parsimony and likelihood analyses showed the Can SINE to be significantly different from TR-i-I in rates of evolution and phylogenetic hypotheses supported. The substitution rate is significantly higher in Can SINE than in TR-i-I, and this is attributable to the tRNA-related region of the insertion. While the incongruence length difference test revealed significant conflict between the Can SINE and TR-i-I partitions, the test was shown to be sensitive to the distribution of homoplasy within partitions. The conflicting phylogenies are likely the result of differences in phylogenetic accuracy (homoplasy distribution) rather than in phylogenetic history (gene trees). The base composition of Can SINE contains a significantly higher GC percentage than TR-i-I. Our results indicate that differences between the two partitions may be the result of homoplasy introduced by an increased substitution rate in the tRNA-related region of Can SINE owing to CpG hypermutability.

Gene trees and hominoid phylogeny.

Here we present a DNA sequence study that incorporates intraspecific variation from all five genera of hominoids (apes and humans). Recently it has been claimed that using single individuals to analyze species' relationships might be misleading if within-species variation is great. Our results indicate that despite high intraspecific variation in mitochondrial cytochrome oxidase subunit II gene sequences of some hominoids, humans and chimpanzees are nonetheless significantly most closely related. We also report the observation that variation within the gorilla species exceeds that between common and pygmy chimpanzee species, a finding with implications for conservation. In contrast, humans are less mitochondrially diverse than lowland gorillas inhabiting western Africa.

Mitochondrial COII sequences and modern human origins.

The aim of this study is to measure human mitochondrial sequence variability in the relatively slowly evolving mitochondrial gene cytochrome oxidase subunit II (COII) and to estimate when the human common ancestral mitochondrial type existed. New COII gene sequences were determined for five humans (Homo sapiens), including some of the most mitochondrially divergent humans known; for two pygmy chimpanzees (Pan paniscus); and for a common chimpanzee (P. troglodytes). COII sequences were analyzed with those from another relatively slowly evolving mitochondrial region (ND4-5). From class 1 (third codon position) sequence data, a relative divergence date for the human mitochondrial ancestor is estimated as 1/27 th of the human-chimpanzee divergence time. If it is assumed that humans and chimpanzees diverged 6 Mya, this places a human mitochondrial ancestor at 222,000 years, significantly different from 1 Myr (the presumed time of an H. erectus emergence from Africa). The mean coalescent time estimated from all 1,580 sites of combined mitochondrial data, when a 6-Mya human-chimpanzee divergence is assumed, is 298,000 years, with 95% confidence interval of 129,000-536,000 years. Neither estimate is compatible with a 1-Myr-old human mitochondrial ancestor. The mitochondrial DNA sequence data from COII and ND4-5 regions therefore do not support this multiregional hypothesis for the emergence of modern humans.

Double-stranded dideoxy sequencing from "dirty" DNA--done in a day.

A rapid method for preparing and directly sequencing plasmid and phagemid miniprep DNA is described. This protocol is a novel combination of two fairly standard procedures, resulting in quick and easy generation of sequence data. The lack of extensive manipulations in the purification process allows the production of DNA sequence data in a single day.

Effect of a new hypoglycemic agent (MDL-310) on glucose metabolism.

N-[3-(dimethylamino)-2-propoxy-2-propenylidene]- N-methylmethanaminium as the iodide or camsylate salt (MDL-310) is a newly reported chemical which has been shown to produce hypoglycemia in vivo. The studies reported here describe in vivo and in vitro effects of MDL-310 on carbohydrate metabolism. In nonfasted mice, MDL-310 decreased liver glycogen and then produced hypoglycemia, concomitant with a near total depletion of liver glycogen stores. In fasted rats, nonhypoglycemic doses of MDL-310 increased glucose production and utilization as determined by tracer studies with [6-3H]glucose. Hypoglycemic doses decreased glucose production and increased blood lactate, which suggests an inhibition of gluconeogenesis. In isolated rat hepatocytes MDL-310, at concentrations of greater than or equal to 5 X 10(-6) M, inhibited gluconeogenesis from lactate (10 mM) plus pyruvate (2 mM). We conclude that the primary action of MDL-310 is to increase glucose utilization and that decreased production due to the inhibition of gluconeogenesis is involved in the hypoglycemic action. A single metabolic action of MDL-310 to increase glycolytic metabolism of glucose is proposed which could explain both the increase in glucose utilization and decrease in glucose production.