Humans and chimpanzees differ in their cellular response to DNA damage and non-coding sequence elements of DNA repair-associated genes.

Compared to humans, chimpanzees appear to be less susceptible to many types of cancer. Because DNA repair defects lead to accumulation of gene and chromosomal mutations, species differences in DNA repair are one plausible explanation. Here we analyzed the repair kinetics of human and chimpanzee cells after cisplatin treatment and irradiation. Dot blots for the quantification of single-stranded (ss) DNA repair intermediates revealed a biphasic response of human and chimpanzee lymphoblasts to cisplatin-induced damage. The early phase of DNA repair was identical in both species with a peak of ssDNA intermediates at 1 h after DNA damage induction. However, the late phase differed between species. Human cells showed a second peak of ssDNA intermediates at 6 h, chimpanzee cells at 5 h. One of four analyzed DNA repair-associated genes, UBE2A, was differentially expressed in human and chimpanzee cells at 5 h after cisplatin treatment. Immunofluorescent staining of gammaH2AX foci demonstrated equally high numbers of DNA strand breaks in human and chimpanzee cells at 30 min after irradiation and equally low numbers at 2 h. However, at 1 h chimpanzee cells had significantly less DNA breaks than human cells. Comparative sequence analyses of approximately 100 DNA repair-associated genes in human and chimpanzee revealed 13% and 32% genes, respectively, with evidence for an accelerated evolution in promoter regions and introns. This is strikingly contrasting to the 3% of DNA repair-associated genes with positive selection in the coding sequence. Compared to the rhesus macaque as an outgroup, chimpanzees have a higher accelerated evolution in non-coding sequences than humans. The TRF1-interacting, ankyrin-related ADP-ribose polymerase (TNKS) gene showed an accelerated intraspecific evolution among humans. Our results are consistent with the view that chimpanzee cells repair different types of DNA damage faster than human cells, whereas the overall repair capacity is similar in both species. Genetic differences in non-coding sequence elements may affect gene regulation in the DNA repair network and thus contribute to species differences in DNA repair and cancer susceptibility.

Primate genomes.

A particular interest in primate genetics was fueled by the release of the complete human genome sequence drafts reported in 2001 by the IHGSC and Celera Genomics. Postgenomic comparative analyses based on the complete genome sequence of the mouse started focusing on functional, evolutionary and diversity aspects of human DNA. By analyzing molecular character states in the representatives of the major primate groups one is able to reconstruct the processes that shape genomes on the lineage to humans after the mouse-human divergence. Consequently, several primate genome sequences are about to be generated during Whole Genome Shotgun (WGS) sequencing projects and are already available for two representatives of the Old World monkeys and hominoids (rhesus monkey, chimpanzee). Comparative data restricted to functional genome parts of a meaningful primate sample (ENCODE project) are underway. These data will yield a definite phylogenetic framework linking the mouse, primate related eutherians and the major primate groups, which is indispensable for any analysis of character evolution. Concerning the functional site comparative genetic research in primates on molecular phenomena that control the spatiotemporal profile of the cellular RNA and protein composition will contribute to our understanding of genotype-phenotype correlations and the emergence of human specific traits.

Organisation of the praesoma of Paratenuisentis ambiguus (Van Cleave, 1921) (Acanthocephala: Eoacanthocephala), with special reference to the lateral sense organs and musculature.

The praesoma of the acanthocephalan parasite Paratenuisentis ambiguus was studied at the light and the electron microscope level, with special reference to the lateral sense organs and the musculature, in order to substantiate the basal pattern of the Acanthocephala and to analyse the phylogeny of the taxon. The study includes the first ultrastructural description of a lateral sense organ in the Acanthocephala. Two sensory support cell ducts extend from the binucleate pericaryon of the sensory support cell to the lateral sense organs. On their way to the lateral sense organs the ducts penetrate the receptacle and join the anterior ventral nerves. Each lateral sense organ consists of a conical termination of one of the sensory support cell ducts, in which the neuronal fibres and dendritic terminations of the equilateral anterior ventral nerve are embedded. An analysis of the available data of praesomal sense organs in Acanthocephala suggests that lateral and apical sense organs are absent in the basal pattern of the Acanthocephala. It is likely that two lateral sense organs, a binucleate sensory support cell with two ducts and two anterior ventral nerves evolved within the stem-line of some Palaeacanthocephala, all Eoacanthocephala and all Archiacanthocephala, whereas two apical sense organs, a quadrinucleate sensory support cell with four ducts and two apical sensory nerves presumably represent an autapomorphic character of the Archiacanthocephala. Furthermore, it can be derived from data in the literature and the present study that the praesomal hooks are totally covered by epidermis in the basal pattern of the Acanthocephala, whereas the ontogenetic loss of the epidermal covering can be regarded as an autapomorphy of the Archiacanthocephala.

Ultrastructure of the acanthella of Paratenuisentis ambiguus (Acanthocephala).

The fine structure of the early acanthella of Paratenuisentis ambiguus (Eoacanthocephala) was investigated. This developmental stage is characterised by losing its ability to move and by differentiation of adult structures. The frontal syncytium, present in the first developmental stage (the acanthor), is lost, while the epidermis and central syncytium persist. The epidermis of the acanthella contains a number of giant nuclei that are arranged into several small groups. The central syncytium is subdivided into different masses, containing nuclei that will give rise to the organs of the adult. The 'uncinogenous bands' extend into the anterior body of the acanthella. Formation of the hooks takes place within these strands. In all investigated stages no extracellular materials were observed. Posterior of the uncinogenous bands lies the brain anlage and the primordia of the reproductive system. Neither a sense organ nor a nervous system were found.

First description of an apical epidermis cone in Paratenuisentis ambiguus (Acanthocephala: Eoacanthocephala) and its phylogenetic implications.

The proboscis apex of the eoacanthocephalan parasite Paratenuisentis ambiguus was studied, using electron and light microscopy, for a better understanding of the parasite's attachment at the intestinal wall of its definitive hosts (Anguilla rostrata and A. anguilla). The results suggest the presence of an epidermis cone with three nuclei at the proboscis apex of P. ambiguus instead of an apical sense organ, as has been previously supposed. Dendritic terminations, sensory nerves and secretory ducts were absent. The existence of many fibres suggests a mechanical function of the epidermis cone. Probably, it presses the proboscis apex and the anterior hooks into the intestinal wall of the definitive host. The presence of an epidermis cone in other eoacanthocephalan species can be derived from data in the literature. The absence of an epidermis cone outside the Eoacanthocephala suggests that it is an evolutionary innovation, supporting the monophyly of the Eoacanthocephala.