Abstract

The second modern synthesis of biology [1] must start with new stratifications and conceptualizations, as well as new ways to connect all of them [2], which are to be perfected through in-depth discussions that may be provoked by seemingly controversial ideas. And new paradigms can thus be built upon the novel thoughts that may eventually converge. As knowledge accumulates based on either newly generated data or frequent visits to old datasets, the new generation of scientists will digest, scrutinize, and cast doubts on the novel thoughts, and all these activities will lead to acceptance or rejection of the new synthesis and its essentials. The knowledge network may either keep growing in multiple dimensions or end temporarily at a single vortex. Trained as a biochemist in college and then a cell biologist early in my scientific career, I only used molecular biology tools to manipulate genes as “parts” and use them to “assemble” certain “operations” and never worried about the genetic background of the cells and animals we used. Some of the tissues (organs) for primary cultures were actually collected from a local slaughter house as byproducts of steaks and sausages and individual samples were often used as a pool. Working on genetics, genomics, and bioinformatics for a couple of decades, I have encountered problems in extending classic concepts of genetics and evolution to explain biological phenomena, especially those defined based on basic concepts of cell biology and biochemistry. My typical example is how to look for genotype-phenotype relationship for indel selection found in the mammalian minimal introns when the selection not only exists in significant numbers but also is predicted to be weak and lacks definable phenotypes in the context of classic genetics [3], [4], [5], although variations of the splice site are often considered as deleterious and attributable to certain inherited diseases [6], [7]. While believing that we still have a long way from the understanding of the Rules of Life, I also reckon we better get started now before it is too late as we always say—a journey of a thousand miles begins with the first step. We now have two tracks of fundamental thinking in biology—geneticists on the one side and cell biologists/biochemists and alike on the other side—informational and operational. The former constructs phenotype-genotype relationship relying on sequence changes in the contexts of populations, species, and lineages, and the latter seeks molecular details leveraging on model systems, such as model organisms and cell lines with less concerns about their generic backgrounds. The future genomics or the modern synthesis of genome biology is to unite the two tracks, of course after some exhaustive discussions. In addition, the differentiation of the two tracks is not to simply draw the boundaries of the two but to seek common grounds for the integration of more information into a knowledge network that connects scientific facts from all fields of biology in a unified realm.

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