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    The main research interests of my laboratory are in understanding the evolutionary dynamics of genomic architecture, content and sequences in different lineages of organisms, and in elucidating its impacts on the evolution of biological novelty and diversity through integrated analyses of genomic, transcriptomic and epigenomic data. These studies tackle fundamental biological questions, but are also directly and indirectly related to many human diseases, especially human cancers. Specifically, current research projects of my laboratory are to apply computational and experimental approaches to address:
    1) evolutionary dynamics of genome architecture and chromosome subtelomeric regions
   
3) genetic basis underlying the evolution of yeast aerobic fermentation
    2) evolution of promoter structure, 5'UTR and gene regulation

Representative studies

Origin and evolution of yeast aerobic fermentation lifestyle

   The most distinctive physiological feature of yeast is aerobic fermentation which is the ability to ferment glucose into ethanol even in the presence of oxygen.  Aerobic fermentation has been used as a diagnostic criterion for tumor cells because many kinds of mammalian tumor cells also undergo fermentative lifestyles. Furthermore, fermentation ethanol is by far the most common type of biofuel produced, accounting for more than 90% of all ethanol production. A better understanding of genetic basis of aerobic fermentation have evolved not only has theoretical implications of great interest, but also can provide a boost for developing therapeutic interventions and engineering complex biological systems to meet our energy needs. 

    Our studies revealed that various factors have contributed to evolution of aerobic fermentation in yeasts (Lin and Li 2011, Lin and Li 2011, Lin and Li 2012, Lin, et al. 2013). These studies were summarized my recent book chapter (Lin and Li 2014).





Lin, Z., et al 2010
   
The promoter struture and gene regulation

    Eukaryotic promoters comprise many classes of transcriptional regulatory elements.  Characterization of promoter structure is crucial for understanding the function and evolution complex network of gene regulation. We examined the spatial distribution of transcription factor binding sites (TFBS), the promoter structural features that may affect such distribution, and the effects of TFBS distribution on transcriptional regulation in S. cerevisiae (Lin et al. 2010). We found that the TFBSs are highly enriched in a narrow window which is ~115 bp upstream to the transcription start site. This distance has been strongly constrained by natural selection, indicating its functional importance.

The role of 5'UTR length in gene regulation
 

    Our recent study also revealed that the lengths of 5’UTR are significantly correlated with gene expression profiles under various conditions. Our data uncovered a strong connection between the change of 5’UTR length and the divergence of gene regulation underlying evolution of aerobic fermentation (Lin and Li 2011a). This study provided the most comprehensive evidence to unveil an important role of 5’UTR length in eukaryotic gene regulation.


Li, Y., et al 2014
Evolution of yeast genome

    To understand how the selection pressure shaped the yeast genome and gene regulation, we determined the genome sequence and transcriptome of a S. cerevisiae strain YHJ7 isolated from Chinese rice wine (Huangjiu), a popular traditional alcoholic beverage in China. We identified many genomic sequence and structural variations in YHJ7, which might play an important role in genomic evolution between strains.



 

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