Genome Evolution

 

Diversity and evolution of Gardnerella vaginalis - friend or foe?

Larry Forney Ph.D. and Roxana Hickey

Bacterial vaginosis (BV) is a common vaginal disorder typified by itching, odor, discharge and elevated risk to sexually transmitted infections. While its exact etiology is unknown, Gardnerella vaginalis has frequently been singled out as the most likely culprit because it is present in nearly all cases of symptomatic BV. However, the bacterium is also detected in many healthy individuals, precluding a definitive link between G. vaginalis and BV in the traditional paradigm of Koch’s postulates of disease. Previous studies suggest the species is highly diverse and may comprise several distinct ‘ecotypes’ with variable association to BV. This study delves into the genomic diversity and evolutionary history of G. vaginalis to identify important gene functions that define this enigmatic species. In addition to genomes from public databases, we are comparing genomic sequences of Gardnerella recovered from the vaginas of healthy girls and women to further explore the species in the context of ‘normal and healthy’ conditions. Collectively, these investigations will provide a broader foundation for understanding the ecology of G. vaginalis in health and disease.

 

Genetic interaction networks and multivariate adaptation

Matthieu Delcourt Ph.D., Tyler Hether, Paul Hohenlohe Ph.D. 

Complex phenotypes are affected by multiple genes, and these genes typically interact with each other in large regulatory networks.  The structure of these networks determines how traits vary and covary with each other and their evolutionary response to selection.  We take two approaches to relate genetic network architecture to multivariate evolution.  First we are using simulation models of simple networks to examine patterns of mutational and genetic variance and the dynamics of adaptation.  Second, we are relating known genetic networks in yeast to traditional quantitative genetic models and testing these models with experimental evolution in the lab.

 

Testing the dynamics of genomic islands of divergence

Tyler Hether, Matthieu Delcourt Ph.D., Paul Hohenlohe Ph.D. 

Natural populations spread across a landscape experience divergent selection – environmental factors that favor different trait variants in different parts of a species’ range.  Genes that affect these traits are expected to diverge as a result, but migration between populations counteracts genetic divergence.  It remains an open question how this balance affects patterns of population differentiation across chromosomes: do genomic regions of divergence grow, shrink, or remain stable?  To address this question, we are combining simulation modeling with experimental evolution in yeast, taking advantage of next-generation sequencing to observe genomic differentiation at a fine scale.

 

LINE-1 activity in mammalian genomes

Holly Wichman Ph.D.

LINE-1 retrotransposons constitute 20% of mammalian genomes and are important drivers of genome evolution.  Although they have been well-characterized in humans and a few model systems, a broader view of their evolutionary dynamics is lacking.  We have undertaken a survey of LINE-1 activity in mammals dating back to the KT boundary to examine the tempo and mode of LINE activity since the mammalian radiation.

 

Evolution of engineered genomes

Holly Wichman Ph.D. and Martina Ederer Ph.D.

The ability to accurately synthesize large segments of DNA has given rise to the promising new field of synthetic biology, where novel functions can be engineered into the organism of choice.   However, the subsequent evolution of such organisms has received little attention.  We have developed a modular system to engineer a small viral genome and are currently using it to investigate the evolutionary stability of viral attenuation by codon modification.