Big flies, small repeats: the "Thr-Gly" region of the period gene in Diptera

The region of the clock gene period (per) that encodes a repetitive tract of threonine-glycine (Thr-Gly) pairs has been compared between Dipteran species both within and outside the Drosophilidae. All the non- Drosophilidae sequences in this region are short and present a remarkably stable picture compared to the Drosophilidae, in which the region is much larger and extremely variable, both in size and composition. The accelerated evolution in the repetitive region of the Drosophilidae appears to be mainly due to an expansion of two ancestral repeats, one encoding a Thr-Gly dipeptide and the other a pentapeptide rich in serine, glycine, and asparagine or threonine. In some drosophilids the expansion involves a duplication of the pentapeptide sequence, but in Drosophila pseudoobscura both the dipeptide and the pentapeptide repeats are present in larger numbers. In the nondrosophilids, however, the pentapeptide sequence is represented by one copy and the dipeptide by two copies. These observations fulfill some of the predictions of recent theoretical models that have simulated the evolution of repetitive sequences.      

Function of the mammalian postorbital bar

Complete postorbital bars, bony arches that encompass the lateral aspect of the eye and form part of a circular orbit, have evolved homoplastically multiple times during mammalian evolution. Numerous functional hypotheses have been advanced for postorbital bars, the most promising being that postorbital bars function to stiffen the lateral orbit in taxa that have significant angular deviation between the temporal fossa and the bony orbit. Without a stiff lateral orbit the anterior temporalis muscle and fascia potentially would pull on the postorbital ligament, deform the orbit, and cause disruption of oculomotor precision. Morphometric data were collected on 1,329 specimens of 324 taxa from 16 orders of extant eutherian and metatherian mammals in order to test whether the orientation of the orbit relative to the temporal fossa is correlated with the replacement of the postorbital ligament with bone. The allometric and ecological influences on orbit orientation across mammals are also explored. The morphometric results corroborate the hypothesis: Shifts in orbit orientation relative to the temporal fossa are correlated with the size of the postorbital processes, which replace the ligament. The allometric and ecological factors that influence orbit orientation vary across taxa. Postorbital bars stiffen the lateral orbital wall. Muscle pulleys, ligaments, and other connective tissue attach to the lateral orbital wall, including the postorbital bar. Without a stiff lateral orbit, deformation due to temporalis contraction would displace soft tissues contributing to normal oculomotor function.     

Dissection of a metastatic gene expression signature into distinct components

Background

Metastasis, the process whereby cancer cells spread, is in part caused by an incompletely understood interplay between cancer cells and the surrounding stroma. Gene expression studies typically analyze samples containing tumor cells and stroma. Samples with less than 50% tumor cells are generally excluded, thereby reducing the number of patients that can benefit from clinically relevant signatures.

Results

For a head-neck squamous cell carcinoma (HNSCC) primary tumor expression signature that predicts the presence of lymph node metastasis, we first show that reduced proportions of tumor cells results in decreased predictive accuracy. To determine the influence of stroma on the predictive signature and to investigate the interaction between tumor cells and the surrounding microenvironment, we used laser capture microdissection to divide the metastatic signature into six distinct components based on tumor versus stroma expression and on association with the metastatic phenotype. A strikingly skewed distribution of metastasis associated genes is revealed.

Conclusion

Dissection of predictive signatures into different components has implications for design of expression signatures and for our understanding of the metastatic process. Compared to primary tumors that have not formed metastases, primary HNSCC tumors that have metastasized are characterized by predominant down-regulation of tumor cell specific genes and exclusive up-regulation of stromal cell specific genes. The skewed distribution agrees with poor signature performance on samples that contain less than 50% tumor cells. Methods for reducing tumor composition bias that lead to greater predictive accuracy and an increase in the types of samples that can be included are presented.     

Relative Wulst volume is correlated with orbit orientation and binocular visual field in birds

In mammals, species with more frontally oriented orbits have broader binocular visual fields and relatively larger visual regions in the brain. Here, we test whether a similar pattern of correlated evolution is present in birds. Using both conventional statistics and modern comparative methods, we tested whether the relative size of the Wulst and optic tectum (TeO) were significantly correlated with orbit orientation, binocular visual field width and eye size in birds using a large, multi-species data set. In addition, we tested whether relative Wulst and TeO volumes were correlated with axial length of the eye. The relative size of the Wulst was significantly correlated with orbit orientation and the width of the binocular field such that species with more frontal orbits and broader binocular fields have relatively large Wulst volumes. Relative TeO volume, however, was not significant correlated with either variable. In addition, both relative Wulst and TeO volume were weakly correlated with relative axial length of the eye, but these were not corroborated by independent contrasts. Overall, our results indicate that relative Wulst volume reflects orbit orientation and possibly binocular visual field, but not eye size.