December 25th, Tuesday 12:15, Room 5007 Rabin Building

** NOTE SPECIAL TIME AND PLACE **

Title: Hypoxia-induced mammalian evolution in biomedical studies: biological and computational challenges

Lecturer: Assaf Malik

Lecturer homepage : http://evolution.haifa.ac.il/index.php/people/postdocs-and-graduate-students-/item/132-assaf-malik_phd

Affiliation : Institute of Evolution

 

Background: Genomic, genetic, and epigenetic changes between species and populations are known to underlie fundamental differences in morphology, physiology, behavior, perception, life-span, and susceptibility to environmental-stress and disease. Accordingly, comparative genomics studies aim in identifying molecular changes which lead to functional differences between individuals, populations, and species. Novel high throughput molecular tools that emerged in the last few years, such as RNA-Seq, now allow cost-effective comparisons across entire genomes, epigenomes, and transcriptomes. These technologies allow revealing new layers of biological complexity, and call for novel computational tools and approaches in comparative genomics.

Our biological model: The development of complex responses to hypoxia (deprived oxygen supply) has played a key role in the evolution of mammals, as inadequate response to this condition is frequently associated with cardiovascular diseases, developmental disorders, and cancers. In our ongoing comparative-genomics project we have performed whole-genomes comparisons between hypoxia-tolerant and hypoxia-sensitive species. As a model animal for hypoxia-tolerance we study the mole rat, which is a unique blind rodent that lives under 6% oxygen in dark underground environments, and survives 3% oxygen in laboratory conditions. The genome of mole rat was sequenced, and will be published in the next months. Recently we sequenced >15,000 mole rat genes, and among them >3,000 genes were found to be activated during hypoxia in the mole rat.

Analytical challenges: Large scale comparative genomic studies entail multiple analytical problems and challenges, which are only partly addressed by existing tools. In the context of our hypoxia-evolution research, some of the most important analytical challenges that we face now are: (1) Identification of molecular events with special adaptive importance, along the evolution of the mole rats. Such types of events include expansions and contractions of genes families, genomic regions, positively-selected mutations, and epigenetic changes; (2) Identification of changes in the connectivity and dynamics of large-scale gene networks that control stress-induced mechanisms, between hypoxia-tolerant and hypoxia-sensitive species (systems biology). Such changes have invaluable potential in biomedical studies; (3) identifying molecular events that correlate with the degeneration of Spalax visual pathways.