engleski

Evolutionary background of human cancer-associated genes explained by sponges

Over the last few years, cancer-associated genes gain more research interest from an evolutionary perspective. Cancer is known as a disease of multicellular animals caused by the errors within the multicellular system, leading to the proliferation of "selfish" cell lines. It had most likely appeared in parallel with multicellularity and the development of true tissues, since comparative genomics studies have shown that many genes linked to human cancer were already present in simple non-bilaterian animals, such as sponges (Porifera). Nevertheless, their function and mechanisms of action still remain unknown. Despite of their simple morphology, with only few cell types and without true tissues and organs, sponges possess complex genomes harbouring many genes highly similar to their vertebrate homologs. Therefore, they provide an excellent model for studying the evolution of different genes that were most possibly present in the genome of animal ancestor. To get a broader insight into the evolutionary history of cancer, we have identified and characterized a number of sponge homologs of human genes associated with cancer development, such as Myc and Ras. Analyses of the primary gene structure and positions of introns have revealed that these genes show similarity in primary, but also in the predicted secondary and tertiary structures, to their homologs in "higher" animals. The phylogenetic analysis implies that sponge homologs of cancer- associated genes are highly conserved when compared to the cancer-associated genes in "higher" animals. Altogether, our work indicates that sponge proteins probably reflect the structures of ancestral proteins present in the last common ancestor of all animals, which have probably had similar properties as their homologs from the extant complex animals. Our next goal is to biochemically characterize the selected sponge homologs of cancer-associated genes and compare their structures and functions to their human homologs. We expect that a deeper insight into the physiological properties of cancer-related homologues in sponges will help to explain their complex interactions in humans and hopefully improve our overall understanding of this disease.

sponges ; cancer ; myc ; ras

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