Research

Our research interests are focused on microbial genome evolution. Our current focuses include the study of DNA acquisition dynamics in natural environments, the evolution of protein interaction with the chaperones and the evolution of phenotypic diversity in cyanobacteria. In our research we use both computational and experimental approaches. 


 

Microbial genome evolution by lateral gene transfer

Lateralgenetransfer

Lateral gene transfer by transformation. 

(Popa and Dagan (2011) Curr Opin Microbiol 14:615-623; Illustration: S. Kilian)

Lateral gene transfer (LGT) is the process by which prokaryotes acquire DNA across wide taxonomic boundaries and incorporate it into their genome. Accumulating evidence shows that LGT, a distinctly non-treelike evolutionary process, plays a major role in prokaryote evolution. Virtually all prokaryotic gene families have been affected by LGT and only few gene families are resistant to it. The biological and evolutionary significance of lateral gene transfer has broad implications for our understanding of microbial biology, not only in terms of evolution, but also in terms of human health: both the emergence of antibiotic resistance and the emergence of novel infectious diseases themselves often results from bacterial virulence mechanisms that can be newly acquired, for example in the form of pathogenicity islands, via LGT.

Because of the workings of the known LGT mechanisms in nature over time, prokaryote genome evolution is not strictly tree-like, but instead a directed network, with a tree-like component linking many genes but simultaneously with a non-tree-like component linking just as many genes in donor-recipient relationships. We apply directed networks to the study of prokaryotic genome evolution in an evolutionary model that allows both for vertical inheritance and for lateral gene transfer events. With methods to identify gene donors, all recent LGTs can be described in a single directed network. Using the directed LGT network we study trends in - and barriers to - LGT during microbial evolution.

taxonomic group

The directed network of recent lateral gene transfers. Node color corresponds to the taxonomic group of donors and recipients listed at the bottom. Connected components of endosymbionts are marked with numbers: (1) Helicobacter, (2) Coxiella, (3) Bartonella, (4) Leptospira, (5) Legionella, (6) Ehrlichia. Clusters of cyanobacteria are marked with letters: (a) high-light adapted Prochlorococcus, (b) low-light adapted Prochlorococcus, (c) marine Synechococcus, (d) other Synechococcus, (e) Nostocales and Chroococcales. Enlarged images of clusters (right) are marked with asterisks. Species names are written by the vertices. Annotations of transferred genes appear next to the edges. (Popa et al. (2011) Genome Res, 21:599-609.)

Further reading: Popa O, Dagan T (2011) Trend and barriers to lateral gene transfer in prokaryotes, Curr Opin Microbiol, 14:615-623.


 

Our research is supported by an ERC Starting Grant, Acronym: EVOLATERAL

EU-Flag ERC


 

The impact of chaperone-mediated folding on genome evolution

Protein folding by the chaperones

Protein folding by the chaperones (Credit: S. Kilian).

Proteins are the building blocks of all living cells. Much like origami, proteins function only in their properly folded state. Proteins unfold under heat. This is why we can sterilize things by boiling or cooking. A cell with few unfolded proteins can recover with specialized helping-hand proteins called chaperones that refold misfolded proteins, but a cell full to the brim with misfolded protein cannot recover and is headed for early death. Many diseases of humans take root in protein folding, such as Alzheimer, where the accumulation of misfolded protein is the hallmark mechanism of disease and the point of attack for treatment. The question of who folds whom - and why - is still wide open. 


In our research we found that chaperones have been leading a second life as a stimulant of genome evolution. Apparently, the folding assistance supplied by the chaperones compensates for many mutations within the genes, resulting in accelerated evolutionary rates in proteins that require chaperones. Current research in our institute is focused on the evolution of protein interaction with the chaperones and the cumulative impact of chaperone mediated folding on genome evolution.


Evolution of multicellular, heterocystous cyanobacteria

heterocystous-cyanobacteria 

Trichome and cell morphology of two representatives of heterocystous, true-branching (Subsection V) cyanobacteria. (A) Fischerella muscicola PCC 7414, forming true lateral branches. (B) Chlorogloeopsis fritschii PCC 6912, undergoing cell divisions in more than one plane but never producing lateral branches. Heterocysts are marked by an orange arrow; hormogonia are marked by a cyan arrow. (Dagan et al. (2012), submitted; Credit: K. Stucken).

Cyanobacteria perform oxygenic photosynthesis as their main energy source. They inhabit marine and freshwater ecosystems as well as terrestrial habitats including hot springs, brackish water and deserts. They shaped Earth's history through the production of atmospheric oxygen starting >2.3 Gyr ago. Today they are important primary producers and major players in global oxygen and carbon cycles, while diazotrophic forms are also key in the global nitrogen budget. Some cyanobacteria possess heterocysts, specialized N2-fixing cells, and heterocyst-forming species are often found in endosymbioses with plants, bryophytes and fungi, typically supplying fixed nitrogen to the host. Cyanobacteria also figure prominently proposals for biological fuel production.

Though monophyletic in origin, cyanobacteria are highly diverse in their phenotypic and genotypic traits. Cyanobacteria are traditionally classified into five morphological classes ranging from unicellular to multicellular cell differentiated forms (Subsections IV and V). All members of Subsections IV and V cyanobacteria form heterocysts, which fix N2 in the presence of O2. Some may also differentiate hormogonia (motile filaments) and akinetes (spore-like cells). A unique aspect of Subsection V is their ability to undergo multiplanar cell division, thereby generating multiseriate filaments or filaments perpendicular to the primary trichomes that are termed "true-branches" which together with their ability of cell differentiation pose them among the more complex prokaryotes. 
Our research is focused on the evolution of cell differentiation in cyanobacteria using as model Subsection V cyanobacteria. This includes a bioinformatic prediction of proteins putatively involved in the true-branching phenotype and their experimental validation in the laboratory.