Methods for computing the standard errors of branching points in an evolutionary tree and their application to molecular data from humans and apes

Statistical methods for computing the standard errors of the branching points of an evolutionary tree are developed. These methods are for the unweighted pair-group method-determined (UPGMA) trees reconstructed from molecular data such as amino acid sequences, nucleotide sequences, restriction-sites data, and electrophoretic distances. They were applied to data for the human, chimpanzee, gorilla, orangutan, and gibbon species. Among the four different sets of data used, DNA sequences for an 895-nucleotide segment of mitochondrial DNA (Brown et al. 1982) gave the most reliable tree, whereas electrophoretic data (Bruce and Ayala 1979) gave the least reliable one. The DNA sequence data suggested that the chimpanzee is the closest and that the gorilla is the next closest to the human species. The orangutan and gibbon are more distantly related to man than is the gorilla. This topology of the tree is in agreement with that for the tree obtained from chromosomal studies and DNA-hybridization experiments. However, the difference between the branching point for the human and the chimpanzee species and that for the gorilla species and the human-chimpanzee group is not statistically significant. In addition to this analysis, various factors that affect the accuracy of an estimated tree are discussed.      

A Z-mammaplasty with minimal scarring

An improved technique for reduction mammaplasty is described that has the advantage of giving a satisfactory final shape to the breast while producing a minimal scar. The method involves periareolar deepithelialization with displacement of the nipple-areola complex, partial subcutaneous mastectomy at the base of the mammary cone, and a Z-plasty to interlock two triangles of skin left after the removal of a little excess skin in the region above the inframammary fold. The Z-plasty adds skin vertically to the inferior pole, resulting in a better final shape and reducing tension around the areola. Any further excess skin is left to retract spontaneously. The best indications for this operation are in young women with elastic skin free of striae "gravidarum." Our experience now covers 53 patients aged 14 to 30 years with reductions of up to 900 gm per breast, and we have encountered no major complications over a 3-year follow-up period.     

A highly conserved nuclear gene for low-level phylogenetics: elongation factor-1 alpha recovers morphology-based tree for heliothine moths

Molecular systematists need increased access to nuclear genes. Highly conserved, low copy number protein-encoding nuclear genes have attractive features for phylogenetic inference but have heretofore been applied mostly to very ancient divergences. By virtue of their synonymous substitutions, such genes should contain a wealth of information about lower-level taxonomic relationships as well, with the advantage that amino acid conservatism makes both alignment and primer definition straightforward. We tested this postulate for the elongation factor-1 alpha (EF-1 alpha) gene in the noctuid moth subfamily Heliothinae, which has probably diversified since the middle Tertiary. We sequenced 1,240 bp in 18 taxa representing heliothine groupings strongly supported by previous morphological and allozyme studies. The single most parsimonious gene tree and the neighbor-joining tree for all nucleotides show almost complete concordance with the morphological tree. Homoplasy and pairwise divergence levels are low, transition/transversion ratios are high, and phylogenetic information is spread evenly across gene regions. The EF-1 alpha gene and presumably other highly conserved genes hold much promise for phylogenetics of Tertiary age eukaryote groups.      

Mesodern-inducing factors and mesodermal patterning

Identification of the signalling molecules involved in mesoderm formation in amphibian embryos still presents problems. None of the original candidates, such as activin, have been definitively ruled out, and the new factors, such as the nodal-related genes, have come on to the scene. Of the original candidates, activin has been definitively shown to act as a morphogen, whereas bone morphogenetic protein (BMP)-4 has emerged as a ventral inducer and an inhibitor of neural differentiation. The effects of BMP-4 are antagonized by chordin, a molecule related to the product of the Drosophila gene short gastrulation.     

Differential susceptibility to a trematode parasite among genotypes of the Mytilus edulis/galloprovincialis complex

We show that parasitism by the trematode Prosorhynchus squamatus in parental and introgressed Mytilus edulis/galloprovincialis (Bivalvia) mussels occurs in individuals with a predominantly M. edulis genome. This result suggests that the restricted specificity of P. squamatus is dependent on genetic factor(s) present in M. edulis. Because of its strong pathogenic effects (i.e. total castration and possible death), this parasite may be a source of intense selection against M. edulis genomes when they are present in a site. As a consequence, it may favour the geographic extension of the M. galloprovincialis genome. Previous studies have indicated that, in hybrid zones, recombinant genotypes are more susceptible to parasitic infections than either parental genotype. We demonstrate that this is not the case for the M. edulis/M. galloprovincialis system, and that the parental genotype alone determines susceptibility.     

A cyclopeptidic suicide substrate preferentially inactivates urokinase-type plasminogen activator.

c[Arg-aB-(CH2+SCH3 phi)-Gly4] was designed and studied as a mechanism-based inactivator (suicide substrate) for plasminogen activators (u-PA and t-PA) and plasmin. This compound inhibited u-PA and fulfills criteria expected for the involvement of an enzyme-activated inhibitor: first-order and irreversible process, saturation kinetics, protection by substrate. The limiting first-order rate constant kinact and the apparent enzyme-inhibitor dissociation constant KI were 0.021 s-1 and 9 microM, respectively at pH 7.5 and 25 degrees C. The activation of plasminogen by u-PA is compromised after this enzyme has been treated by the reagent. Plasmin and t-PA were inactivated 40- and 2330-fold less efficiently than u-PA, respectively.