Our research focuses on innovations and mechanisms that either facilitate or constrain evolutionary changes. Our main focus has been on conservation of the early organogenesis stage in vertebrates and on conservation of adult traits that are determined during that stage (i.e. the number of cervical vertebrae in mammals and the number of digits in tetrapods). We have found strong support for the important role of internal selection in shaping the adaptive evolution of body plans (i.e. selection caused by characteristics of the developmental system). Our data on internal selection have implications for human morbidity and lethality.

The data show that the presence of a modification of an evolutionary conserved structure, such as the presence of a rib on the seventh vertebra (a cervical rib, i.e. a change in the number of cervical vertebrae), can be used as a reliable indicator of disturbances of early embryogenesis (Collaboration with Liliane Wijnaendts, Free University Medical Centre (VUMC). We have made use of this aspect in a study on the effects of hormonal treatments that are usually part of In Vitro Fertilization (IVF) treatments. Using cervical rib frequencies we have shown that in mice Ovarian Hyper Stimulation (OHS) treatments have a continued effect on the mother during early pregnancy and lead to a disturbance of early organogenesis organogenesis (Collaboration with Frans Helmerhorst, Leiden University Medical Centre (LUMC). We hope to further investigate the effects of different OHS treatments on early gene activity in mice to explore the genetic basis of pleiotropic effects associated with cervical ribs.

Giraffe and dugong skeletons

Mammals have seven cervical vertebrae, regardless of the length of the neck. Bottom left: giraffe; top right: dugong. Reproduced from Owen (1866).

We have also studied the conservation of the early organogenesis stage in insects. We found that the robustness of the gene networks of the early organogenesis stage against mutational changes is surprisingly low. As a result of this, mutations have many associated effects and are usually deleterious (internal selection against mutations).

The results of our study on the conservation of the number of digits provides an important argument in the current controversy on the descent of birds from dinosaurs between developmental biologists and paleontologists. Our data on the evolutionary conservation of digit development are in support of the views of many developmental biologists that the identity of the digits in the wing of birds cannot be homologous to the identity of digits in the forelimbs of their hypothesized dinosaur ancestors, unless the identity of digits in theropods is erroneous. We have, therefore, proposed a re-appraisal of the fossil digit data of dinosaurs.

We have also studied developmental constraints in dogs, i.e. the negative consequences (pleiotropic effects) associated with extreme artificial selection for size in dogs (Collaboration with Marc Nussbaumer of the Natural History Museum, Berne, Switzerland). We have shown that for dogs the wide-spread notion that lifespan decreases with size is based on a misinterpretation of the data. We have shown, in a meta-analysis of the literature, that the very early deaths in dogs from large breeds are to an important extent the result of developmental diseases associated with the extremely high growth rates that have been co-selected with size.

Giant dog breed skulls

The size of giant dog breeds (Great Dane, Newfoundland, St. Bernard dog, Irish Wolfhound) has remarkably increased during the last century, as shown here for St. Bernhard dogs. The breed standard for St. Bernard dogs now specifies a shoulder height of between 70-90 cm and these dogs weigh 65-85 kg, whereas a typical 19th century dog was approx. 60 cm high and weighed less than 50 kg. The extremely high growth rates in large breeds are associated with serious health problems, such as bone cancer and hip dysplasia. Top left: male, 1968; top right: female, 2001; bottom left: male, 1893; bottom right: female, ca. 1880-1890.

Finally, we collaborate with Lauren Chapman of McGill University (Montreal, Canada) to study the role of phenotypic plasticity (changes induced by the environment) and genetic assimilation in the process of adaptation and evolutionary change of cichlid fishes. We found that initial phenotypic changes (non-heritable changes) appear to facilitate the genetic assimilation of changes.