Molecular phylogeny of the hominoids: inferences from multiple independent DNA sequence data sets

Consensus on the evolutionary relationships of humans, chimpanzees, and gorillas has not been reached, despite the existence of a number of DNA sequence data sets relating to the phylogeny, partly because not all gene trees from these data sets agree. However, given the well-known phenomenon of gene tree-species tree mismatch, agreement among gene trees is not expected. A majority of gene trees from available DNA sequence data support one hypothesis, but is this evidence sufficient for statistical confidence in the majority hypothesis? All available DNA sequence data sets showing phylogenetic resolution among the hominoids are grouped according to genetic linkage of their corresponding genes to form independent data sets. Of the 14 independent data sets defined in this way, 11 support a human- chimpanzee clade, 2 support a chimpanzee-gorilla clade, and one supports a human-gorilla clade. The hypothesis of a trichotomous speciation event leading to Homo; Pan, and Gorilla can be firmly rejected on the basis of this data set distribution. The multiple-locus test (Wu 1991), which evaluates hypotheses using gene tree-species tree mismatch probabilities in a likelihood ratio test, favors the phylogeny with a Homo-Pan clade and rejects the other alternatives with a P value of 0.002. When the probabilities are modified to reflect effective population size differences among different types of genetic loci, the observed data set distribution is even more likely under the Homo-Pan clade hypothesis. Maximum-likelihood estimates for the time between successive hominoid divergences are in the range of 300,000-2,800,000 years, based on a reasonable range of estimates for long-term hominoid effective population size and for generation time. The implication of the multiple-locus test is that existing DNA sequence data sets provide overwhelming and sufficient support for a human-chimpanzee clade: no additional DNA data sets need to be generated for the purpose of estimating hominoid phylogeny. Because DNA hybridization evidence (Caccone and Powell 1989) also supports a Homo-Pan clade, the problem of hominoid phylogeny can be confidently considered solved.      

Role of MSC-derived galectin 3 in the AML microenvironment

In acute myeloid leukemia (AML), high Galectin 3 (LGALS3) expression is associated with poor prognosis. The role of LGALS3 derived from mesenchymal stromal cells (MSC) in the AML microenvironment is unclear; however, we have recently found high LGALS3 expression in MSC derived from AML patients is associated with relapse. In this study, we used reverse phase protein analysis (RPPA) to correlate LGALS3 expression in AML MSC with 119 other proteins including variants of these proteins such as phosphorylated forms or cleaved forms to identify biologically relevant pathways. RPPA revealed that LGALS3 protein was positively correlated with expression of thirteen proteins including MYC, phosphorylated beta-Catenin (p-CTNNB1), and AKT2 and negatively correlated with expression of six proteins including integrin beta 3 (ITGB3). String analysis revealed that proteins positively correlated with LGALS3 showed strong interconnectivity. Consistent with the RPPA results, LGALS3 suppression by shRNA in MSC resulted in decreased MYC and AKT expression while ITGB3 was induced. In co-culture, the ability of AML cell to adhere to MSC LGALS3 shRNA transductants was reduced compared to AML cell adhesion to MSC control shRNA transductants. Finally, use of novel specific LGALS3 inhibitor CBP.001 in co-culture of AML cells with MSC reduced viable leukemia cell populations with induced apoptosis and augmented the chemotherapeutic effect of AraC. In summary, the current study demonstrates that MSC-derived LGALS3 may be critical for important biological pathways for MSC homeostasis and for regulating AML cell localization and survival in the leukemia microenvironmental niche.     

New World monkey phylogeny based on X-linked G6PD DNA sequences

The Platyrrhini, or New World monkeys, are an infraorder of Primates comprised of 16 genera. Molecular phylogenetic analyses have consistently sorted these genera into three groups: the Pitheciidae (e.g., saki and titi monkeys), Atelidae (e.g., spider and howler monkeys), and Cebidae (e.g., night monkeys, squirrel monkeys, and tamarins). No consensus has emerged on the relationships among the three groups or within the Cebidae. Here, approximately 0.8 kb of newly generated intronic DNA sequence data from the X-linked glucose-6-phosphate dehydrogenase (G6PD) locus have been collected from nine New World monkey taxa to examine these relationships. These data are added to 1.3 kb of previously generated G6PD intronic DNA sequence data [Mol. Phylogenet. Evol. 11 (1999) 459]. Using distance and parsimony-based techniques, G6PD sequences provide support for an initial bifurcation between the Pitheciidae and the remaining platyrrhines, linking Atelidae and Cebidae as sister taxa. Bayesian methods provided a conflicting phylogeny with Atelidae as outgroup. Within the Cebidae, a sister relation between Aotus and the Cebus/Saimiri clade is favored by parsimony analysis, but not by other analyses. Potential reasons for the difficulty in resolving family level New World monkey phylogenetics are discussed.     

Accelerated evolution of the ASPM gene controlling brain size begins prior to human brain expansion

Primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by global reduction in cerebral cortical volume. The microcephalic brain has a volume comparable to that of early hominids, raising the possibility that some MCPH genes may have been evolutionary targets in the expansion of the cerebral cortex in mammals and especially primates. Mutations in ASPM, which encodes the human homologue of a fly protein essential for spindle function, are the most common known cause of MCPH. Here we have isolated large genomic clones containing the complete ASPM gene, including promoter regions and introns, from chimpanzee, gorilla, orangutan, and rhesus macaque by transformation-associated recombination cloning in yeast. We have sequenced these clones and show that whereas much of the sequence of ASPM is substantially conserved among primates, specific segments are subject to high Ka/Ks ratios (nonsynonymous/synonymous DNA changes) consistent with strong positive selection for evolutionary change. The ASPM gene sequence shows accelerated evolution in the African hominoid clade, and this precedes hominid brain expansion by several million years. Gorilla and human lineages show particularly accelerated evolution in the IQ domain of ASPM. Moreover, ASPM regions under positive selection in primates are also the most highly diverged regions between primates and nonprimate mammals. We report the first direct application of TAR cloning technology to the study of human evolution. Our data suggest that evolutionary selection of specific segments of the ASPM sequence strongly relates to differences in cerebral cortical size.     

Visible Light Induces Melanogenesis in Human Skin through a Photoadaptive Response

Visible light (400–700 nm) lies outside of the spectral range of what photobiologists define as deleterious radiation and as a result few studies have studied the effects of visible light range of wavelengths on skin. This oversight is important considering that during outdoors activities skin is exposed to the full solar spectrum, including visible light, and to multiple exposures at different times and doses. Although the contribution of the UV component of sunlight to skin damage has been established, few studies have examined the effects of non-UV solar radiation on skin physiology in terms of inflammation, and limited information is available regarding the role of visible light on pigmentation. The purpose of this study was to determine the effect of visible light on the pro-pigmentation pathways and melanin formation in skin. Exposure to visible light in ex-vivo and clinical studies demonstrated an induction of pigmentation in skin by visible light. Results showed that a single exposure to visible light induced very little pigmentation whereas multiple exposures with visible light resulted in darker and sustained pigmentation. These findings have potential implications on the management of photo-aggravated pigmentary disorders, the proper use of sunscreens, and the treatment of depigmented lesions.     

Infants Time Their Smiles to Make Their Moms Smile

One of the earliest forms of interaction between mothers and infants is smiling games. While the temporal dynamics of these games have been extensively studied, they are still not well understood. Why do mothers and infants time their smiles the way they do? To answer this question we applied methods from control theory, an approach frequently used in robotics, to analyze and synthesize goal-oriented behavior. The results of our analysis show that by the time infants reach 4 months of age both mothers and infants time their smiles in a purposeful, goal-oriented manner. In our study, mothers consistently attempted to maximize the time spent in mutual smiling, while infants tried to maximize mother-only smile time. To validate this finding, we ported the smile timing strategy used by infants to a sophisticated child-like robot that automatically perceived and produced smiles while interacting with adults. As predicted, this strategy proved successful at maximizing adult-only smile time. The results indicate that by 4 months of age infants interact with their mothers in a goal-oriented manner, utilizing a sophisticated understanding of timing in social interactions. Our work suggests that control theory is a promising technique for both analyzing complex interactive behavior and providing new insights into the development of social communication.