7th round table

March 21, 2014

Ancestral and recent population genomics
Carolin KosiolInstitute of Population Genetics, Vetmeduni Vienna

"Walking Pathways" and cancer
Alexander KelgeneXplain GmbH, Germany

 

 

Ancestral and recent population genomics
Carolin KosiolInstitute of Population Genetics, Vetmeduni Vienna

The increased availability of sequenced genomes both from closely related species and from individuals of the same species, offers a great opportunity to study the speciation and evolutionary history of populations, provided we can properly model the process of sequence evolution using inter and intraspecific data together.

In my group, we have developed a new method called POlymorphisms-aware phylogenetic MOdel (POMO). With this approach, we naturally account for incomplete lineage sorting and shared ancestral polymorphisms. Our method can accurately and time-efficiently estimate the parameters describing evolutionary patterns for phylogenetic trees of any shape (species trees, population trees, or any combination of those). I will present what can be learned by applying these methods to genome-wide data sites of human, chimpanzee, and two orang-utan species about ancestral population history of these species. Finally, I will also discuss how these new methods could be applied to populations of fruit flies that have recently been subject to an experimental evolution study for temperature adaptation in our institute.

  

"Walking Pathways" and cancer
Alexander KelgeneXplain GmbH, Germany

"If our genes are so similar, what really makes a human different from E. coli? The answer lies in the difference in [mechanisms of] gene regulation used." (Nature education, 2008). In this presentation we will discuss the evolutional advantages of high plasticity of gene regulatory networks that is a characteristic of multicellular eukaryotic organisms. At the same time these advantages come with the price - terrible diseases such as cancer. Non-reversible structural changes of the regulatory networks due to an epigenetic "evolution" of genome regulatory regions provide the basis for realization of normal development programs. On the other side they may cause transformations switching the normal state to a disease state. We refer to such structural network changes as "walking pathways".

The analysis of this phenomenon helps us to understand the mechanisms of molecular switches (e.g. between programs of cell death and programs of cell survival) and to identify prospective drug targets for cancer therapy. The structural plasticity of regulatory networks leads to formation of personalized variants of regulatory pathways in individual tumors, which requires reverse engineering and de novo reconstruction of pathways in each individual case. Such structural plasticity of regulatory networks observed in genomes of higher eukaryotes, in our view, is the result of an evolutional "aramorphose" towards emergence of completely new mechanism of evolution of multi-cellular organisms.