Biology subjects

Papp, B.

Publications and source records attributed to Papp, B..

23 records · Page 2Linked to original sources

bioRxiv2019

Unmatched level of molecular convergence among deeply divergent complex multicellular fungi

Convergent evolution is pervasive in nature, but it is poorly understood how various constraints and natural selection limit the diversity of evolvable phenotypes. Here, we report that, despite >650 million years of divergence, the same genes have repeatedly been co-opted for the development of complex multicellularity in the two largest clades of fungi--the Ascomycota and Basidiomycota. Co-opted genes have undergone duplications in both clades, resulting in >81% convergence across shared multicellularity-related families. This convergence is coupled with a rich repertoire of multicellularity-related genes in ancestors that predate complex multicellular fungi, suggesting that the coding capacity of early fungal genomes was well suited for the repeated evolution of complex multicellularity. Our work suggests that evolution may be predictable not only when organisms are closely related or are under similar selection pressures, but also if the genome biases the potential evolutionary trajectories organisms can take, even across large phylogenetic distances.

evolutionary biology↗

bioRxiv2019

Chemical-genetic profiling reveals cross-resistance and collateral sensitivity between antimicrobial peptides

Antimicrobial peptides (AMPs) are key effectors of the innate immune system and promising therapeutic agents. Yet, knowledge on how to design AMPs with minimal cross-resistance to human host-defense peptides remains limited. Here, with a chemical-genetic approach, we systematically assessed the resistance determinants of Escherichia coli against 15 different AMPs. Although generalizations about AMP resistance are common in the literature, we found that AMPs with different physicochemical properties and cellular targets vary considerably in their resistance determinants. As a consequence, collateral sensitivity effects were common: numerous genes decreased susceptibility to one AMP while simultaneously sensitized to others. Finally, the chemical-genetic map predicted the cross-resistance spectrum of laboratory-evolved human-B-defensin-3 resistant lineages. Our work substantially broadens the scope of known resistance-modulating genes and explores the pleiotropic effects of AMP resistance. In the future, the chemicalgenetic map could inform efforts to minimize cross-resistance between therapeutic and human host AMPs.

microbiology↗

bioRxiv2018

Phylogenetic barriers to horizontal transfer of antimicrobial peptide resistance genes in the human gut microbiota

The human gut microbiota has adapted to the presence of antimicrobial peptides (AMPs) that are ancient components of immune defence. Despite important medical relevance, it has remained unclear whether AMP resistance genes in the gut microbiome are available for genetic exchange between bacterial species. Here we show that AMP- and antibiotic-resistance genes differ in their mobilization patterns and functional compatibilities with new bacterial hosts. First, whereas AMP resistance genes are widespread in the gut microbiome, their rate of horizontal transfer is lower than that of antibiotic resistance genes. Second, gut microbiota culturing and functional metagenomics revealed that AMP resistance genes originating from phylogenetically distant bacteria only have a limited potential to confer resistance in Escherichia coli, an intrinsically susceptible species. Third, the phenotypic impact of acquired AMP resistance genes heavily depends on the genetic background of the recipient bacteria. Taken together, functional compatibility with the new bacterial host emerges as a key factor limiting the genetic exchange of AMP resistance genes. Finally, our results suggest that AMPs induce highly specific changes in the composition of the human microbiota with implications for disease risks.

microbiology↗

bioRxiv2018

Pathogen diversity drives the evolution of promiscuous peptide binding of human MHC-II alleles

Major histocompatibility complex (MHC) molecules mediate the adaptive immune response against pathogens. Certain MHC alleles are generalists: they present an exceptionally large variety of antigenic peptides. However, the functional implications of such elevated epitope binding promiscuity in the MHC molecules are largely unknown. According to what we term the pathogen-driven promiscuity hypothesis, exposure to a broad range of pathogens favors the evolution of highly promiscuous MHC variants. Consistent with this hypothesis, we found that in pathogen-rich geographical regions, humans are more likely to carry promiscuous MHC class II DRB1 alleles, and the switch between high and low promiscuity levels has occurred repeatedly and in a rapid manner during human evolution. We also show that selection for promiscuous peptide binding shapes MHC genetic diversity. In sum, our study offers a conceptually novel mechanism to explain the global distribution of allelic variants of a key human immune gene by demonstrating that pathogen pressure maintains promiscuous MHC class II alleles. More generally, our work highlights the hitherto neglected role of epitope binding promiscuity in immune defense, with implications for medical genetics and epidemiology.

evolutionary biology↗

bioRxiv2018

Enzyme promiscuity shapes evolutionary innovation and optimization

Evidence suggests that novel enzyme functions evolved from low-level promiscuous activities in ancestral enzymes. Yet, the evolutionary dynamics and physiological mechanisms of how such side activities contribute to systems-level adaptations are poorly understood. Furthermore, it remains untested whether knowledge of an organisms promiscuous reaction set ( underground metabolism) can aid in forecasting the genetic basis of metabolic adaptations. Here, we employ a computational model of underground metabolism and laboratory evolution experiments to examine the role of enzyme promiscuity in the acquisition and optimization of growth on predicted non-native substrates in E. coli K-12 MG1655. After as few as 20 generations, the evolving populations repeatedly acquired the capacity to grow on five predicted novel substrates-D-lyxose, D-2-deoxyribose, D-arabinose, m-tartrate, and monomethyl succinate-none of which could support growth in wild-type cells. Promiscuous enzyme activities played key roles in multiple phases of adaptation. Altered promiscuous activities not only established novel high-efficiency pathways, but also suppressed undesirable metabolic routes. Further, structural mutations shifted enzyme substrate turnover rates towards the new substrate while retaining a preference for the primary substrate. Finally, genes underlying the phenotypic innovations were accurately predicted by genome-scale model simulations of metabolism with enzyme promiscuity. Computational approaches will be essential to synthesize the complex role of promiscuous activities in applied biotechnology and in models of evolutionary adaptation.

systems biology↗