Research Interest

Evolutionary Genomic analysis of human ancient enhancer elements (human-fish conserved)


One of the questions that our group is focusing on is to estimate the evolutionary aspects of subset of human enhancers that are conserved across the vertebrate lineage (human-fish conserved). In addition to increase in number of cis-acting elements (novel regulatory modules), the alternative way through which the modern vertebrates (e.g. mammals) can diversify the tasks of developmental genes, is by increasing the architectural complexity of older enhancer modules. The most plausible scenario for this sort of enhancer evolution is to incorporate binding sites for multiple novel transcriptional factors in the vicinity of existing landscape of minimal functional regulatory element that was defined during early evolution. Under this scenario the complete evolutionary unit of regulatory element in modern vertebrates (such as mammals) would be the combination of new and ancient parts. This increase in architectural complexity and the span of ancient enhancers would help them recruiting for the novel lineage specific developmental task, while retaining the most fundamental aspects of enhancer function conserved across the lineages (for instance, human-fish). To address the above mentioned question our group is employing the combination of computational and functional assays to segregate the evolutionarily older and new components of vertebrate ancient cis-regulatory modules. For this purpose we selected the in vivo model zebrafish to test the functionality of human-fish conserved putative cis-regulatory modules and to dissect their evolutionary trajectories. Understanding the structural architecture and evolutionary dynamics of human enhancers is a prerequisite to elucidate their participation in human inherited disease and vertebrate evolutionary developmental biology.  

Evolutionary conserved enhancers regulating human GLI3 expression in various tissue domains of developing mice embryos

Genomic basis of human biological uniqueness

Primate specific evolutionary history of human HR gene.

Understanding the genetic basis of morphological, physiological, anatomical and behavioral traits that distinguish human from other primates such as bonobo chimpanzees, humans, gorillas and orangutans presents a great challenge to biologists. The degree of genetic similarity among the members of this great ape clade is reflected in the predominantly noncoding orthologous DNA sequences, which from human and chimpanzee nuclear genomes are on average ~98.9% identical, whereas with gorilla orthologs they are on average ~98.5% identical and with orangutan orthologs ~97.0% identical. Despite of this extremely high similarity at the genomic level there is an extensive list of qualitative and quantitative features that distinguish humans from other apes, such as our large brain, bipedalism, small canine teeth, language, advanced tool-making capabilities and hairlessness. Our group has recently analyzed the genetic basis of human hairlessness and has pinpointed the HR gene as a prime candidate in reducing hair cover during the recent history of human evolution. We are exploring further the evolutionary dynamics of this gene to strengthen our argument that HR underwent recent phase of positive selection during human history. Other candidate genes that might be involved in human biological uniqueness are also under investigation in our lab.

Evolution of vertebrate gene families and genomes

Duplication ages of multigene families residing on human HOX-cluster paralogons.

Another area that fascinates me is to explore those events that diversified the human gene sets, and shaped vertebrate genome architecture deep in history (>450 Mya). Unrevealing these events is a key to unfold genomic basis of major morphological transitions that vertebrates accomplished during their history. Currently our group uses the combination of phylogenetic approaches and inter-genomic/intra-genomic synteny comparisons to shed important insight into ancient vertebrate genome shaping events.  

 














Note: Those who are interested in joining our group as a PhD scholar (to explore one of the above mentioned questions) can email me their detailed CV. Candidates from abroad with their own funding source are also welcome to apply.