Dr. Baxevanis' research focuses on the use of phylogenetic and comparative genomic techniques to study developmental proteins that play a fundamental role in the specification of body plan, pattern formation and cell fate determination during metazoan development. His group uses a variety of bioinformatic approaches to understand the evolution and function of these proteins and their ultimate role in human disease.
Building upon his prior work on the origin and early evolution of the Hox genes, Dr. Baxevanis' focus has turned to analyzing the genomes of early branching metazoan phyla in an effort to better understand the relationship between genomic and morphological complexity, as well as the molecular basis for the evolution of novel cell types. Thematically, Dr. Baxevanis' current research interests are centered on probing the interface between genomics and developmental biology and conducting comparative, genomics-based research with an evolutionary point of view. These themes were elucidated in the 2011 document from the National Human Genome Research Institute (NHGRI) outlining a vision for the future of genomic research.
Until recently, only three of the four non-bilaterian metazoan lineages (Porifera, Placozoa, and Cnidaria) had at least one species whose genome had been sequenced. Ctenophora - the comb jellies - remained as the last non-bilaterian animal phylum without a sequenced genome, and its phylogenetic position remained uncertain. With the goal of understanding the molecular innovations that drove the surge in diversity and increasing complexity in early animal evolution, Dr. Baxevanis' group sequenced, assembled, annotated and analyzed the 150-megabase genome of the ctenophore, Mnemiopsis leidyi. By addressing the void in the availability of high-quality, genome-scale sequence data in a critical part of the evolutionary tree, Dr. Baxevanis' group resolved the question of the phylogenetic position of the ctenophores. The results of their phylogenomic analyses strongly suggest that ctenophores are the sister group to all other animals. Based on analyses of gene content, their results also suggest that neural and mesodermal cell types were either lost in Porifera and Placozoa or that to some extent these cell types evolved independently in the ctenophore lineage. These findings challenge long-held ideas regarding not only the phylogenetic position of the ctenophores, but of the evolution of the aforementioned cell types as well.
The availability of these data has also enabled Dr. Baxevanis' group to answer important questions regarding phylogenetic diversity and the evolution of protein families that play a fundamental role in metazoan development. For example, his group showed that Mnemiopsis contains a reduced set of homeodomains, supporting the placement of ctenophores at the base of the Metazoa. His group's work on the Wnt family showed that Wnt antagonists appear to be scarce in Mnemiopsis, suggesting that complex regulation of this pathway probably emerged later in animal evolution. Studies on the evolution of LIM proteins revealed a significant expansion of the LIM superclass at the base of the Metazoa, allowing for the increase in complexity required for the transition from a unicellular to multicellular lifestyle. A comprehensive phylogenetic analysis of the Sox family has provided strong evidence that the ancient primary function of Sox genes was to regulate the maintenance of stem cells and function in cell fate determination. His group also determined that there are no discernible microRNAs in Mnemiopsis and that key components of the microprocessor complex are missing, perhaps indicating a point in evolutionary time that pre-dated the development of additional plasticity in developmental signaling networks.
Finally, as part of an in-depth study yielding the first metazoan phylogeny for the photoprotein gene family, Dr. Baxevanis' group was able to demonstrate co-localized expression of photoprotein genes and two putative opsin genes in developing Mnemiopsis photocytes, showing that these cells have the capacity to both sense and respond to stimuli. This finding is the first reported instance of photoreception and light production being functionally linked in the same cell type of a given organism, which may shed new light on the evolution of the eye.
Dr. Baxevanis' current work is focused on learning how these early branching animals could be used in the context of human disease research. Using a comparative genomics approach based on sequence data from animals across the metazoan tree, his group has found that non-bilaterian genomes contain a surprisingly high number of human disease gene homologs, despite their evolutionarily distant position with respect to humans. The findings from this study support the proposition that non-bilaterian animals have the potential to serve as viable models for studying various important classes of human diseases.
In related work, Dr. Baxevanis is now leading an international effort to sequence two Hydractinia species. The regenerative abilities of these hydrozoan cnidarians make them excellent models for the study of key questions related to pluripotency, allorecognition and stem cell biology, work that will be significantly advanced by the availability of high quality whole-genome sequencing data from these organisms.
Computational Genomics Unit Members
Stephen Bond, Ph.D., Post-Doctoral Fellow
Samantha Klasfeld, Post-Baccalaureate Fellow
Evan Maxwell, Graduate Student, Boston University-NIH Graduate Partnerships Program in Bioinformatics
Christine Schnitzler, Ph.D., Post-Doctoral Fellow
Posted: November 20, 2015