Tit-Yee Wong 王鐵頤 was born in Hong Kong. He received his BS (1974) and MS (1975) from Murray State University, KY, and Ph.D. (1981) from The University of Houston, TX. He moved on to Johns Hopkins University School of Medicine and then to Johns Hopkins University Biology Department for Postdoctoral studies in Biochemistry, Cell Biology, and Microbiology. He joined the faculty of Biological Sciences at the University of Memphis in 1985. He is also a faculty of the Bioinformatics Program. He is currently teaching general microbiology, microbial ecology, and bacterial physiology. He is interested in the bioenergetics of the free-living, N₂-fixing Azotobacter vinelandii and the highly radioresistant bacterium, Deinococcus radiodurans. He also published papers on slime mold (Dictyostelium), alga (Selenastrum & Dinoflagellate), and Zebra Mussels (Dreissena) in various zoological, environmental, and toxicological journals.

Tit-Yee Wong and Robert Maier were the first to use the shortened term “mixotroph” to describe the hydrogen-dependent chemolithoheterotrophic mode of growth of bacteria. The simultaneous use of both organic and inorganic compounds as carbon and energy sources is now considered common among bacteria in the soil.

chemoorganoheterotrophic organisms use organic compounds as their sources of energy and carbon,  Most scientists assume these bacteria would automatically balance the carbons and energy supplies. The electron transport chain in bacteria is branched. Wong is the first to suggest the this branched-chain could be futile and be used to balance the redox level of the cell (an alternative function of the electron transport chain). The electron transport chain can be futile under certain conditions. Another futile metabolism was demonstrated in Deinococcus radiodurans growing on glucose (The DNA excision repair system of the highly radioresistant bacterium Deinococcus radiodurans is facilitated by the pentose phosphate pathway; Molecular Microbiology. 48:1317.1323.)

The  discovery of the Stop Singal ratio in bacterial genomes (Role of premature stop Codons in bacterial evolution. J Bacteriol. 190:6718-25.)

There are many trinucleotide sequences of TAA, TAG, and TGA embedded with the 2nd and  3rd reading frames of a gene. These sequences are called embedded or hidden stop codons. They are thought to be important in ensuring the proper production of the protein. 

The genomes, even within the same species, vary greatly.  The individual genome of a species is marked by sequences due to horizontal gene transfers. Additionally, there are many unique functional unknown genes (the so-called Singletons or Empirical genes) in a genome that are not shared by most members of the same species.

Dr. Wong initially noticed that the fru gene of Deinococcus radiodurans does not have a single TAA and TAG sequences embedded in it (but there are many TGA sequences).  In fact, the TAA and TAG signatures in the entire D. radiodurans genome were extremely low.  Extended studies showed that the ratios of stop codons (TAA: TAG: TGA) on the three reading frames of the genes (termed stop-signals) in the genomes of phylogenetically related bacteria are very similar (DOI: 10.1128/JB.00682-08).  In fact, a bacterium can be represented by using the ratio of the stop-signals ratio of its own genome to for a highly specific 9-vector. For example, Escherichia coli K12 (4289 genes) and E. coli CFT073 (6089 genes), despite the differences in genomic sizes, share a very similar stop-signal (SS) ratio; The SS-ratio of Salmonella typhimurine LTS (4454 genes) is also related to its phylogenetically related counterpart. Whereas the Rickettsia typhi as a totally different SS-ratio

 

Further studies show that the stop-signal ratios of genetically related bacteria are almost identical, regardless of the various sizes of the genomes.   Crusting these stop-signal vectors of many bacteria results in a high-resolution bacterial tree that mimics the phylogenetic tree constructed by other sequence-based methods whole-genome stop-signals ratios.

Using Salmonella species as the outgroup, The Genomic-SS ratio of various E. coli strains are clustered. Members of the same pathotype often share a similar Genomic SS-Ratio.  

Why foreign genes and singletons do not interfere with the SS ratio?

The Chandelier Hypothesis: Insiloco deletion of a few known foreign genes or a few Empirical Protein Genes from calculating the Genomic-SS Ration would result in a very different Genomic-SS ratio, making it incomparable to its phylogenetic related counterparts.

Wong proposes the “Chandelier Hypothesis” to explain the need for the stop-signals trinucleotide regularity in the stability of the physical architecture of the nucleoid.

Genomic SS Ratio may represent the physical structure of the bacterial nucleoid a species. 

The DNA of a bacterium is clustered into a highly compact structure called the nucleoid.  However, the bacterial nucleoid is very dynamic. Bacteria undergo cell division, DNA duplication, transcription, and translation simultaneously.  Enzymes for DNA duplication, transcription, and translation are outside the nucleoid.  While there is good evidence to show that the DNA polymerase dimmer could initiate at the origin of the chromosome and provides the energy need to push the newly formed  DNAs to the two poles of the dividing bacterium,  the traffics mechanism of genes in and out of the core of the nucleoid to the surface of the nucleoid for DNA transcription to RNA by the RNA polymerase and for RNA to be read by the ribosome are not clear.

Wong proposes that the various DNA-binding proteins may create a scaffold in the core of the nucleoid of a bacterium. This scaffold has a large number of stop-signal binding sites, but the ratio of the stop-signal binding sites is also fixed for that species. DNA sticks to the nucleoid but can slide almost freely by binding and unbinding to these stop signals.  This scaffold thus prevents the negatively charged DNA from falling apart and also allows the DNA to move in and out of the core of the nucleoid.

He further suggests that RNA polymerases and ribosomes on the surface of the nucleoid may provide the push and pull energy needed to return the unneeded genes and expose the needed genes from the surface of the nucleoid.