Shi Huang has been a professor of genetics at the Central South University since 2009. Before that he was a professor at the Sanford-Burnham Medical Research Institute for 16 years. He has been working on cancer genetics and epigenetics. His lab cloned the RIZ1/PRDM2/KMT8 histone methyltransferase and proposed an epigenetic pathway of sporadic cancers to account for the risk effects of the Western style diet. He proposed a novel hypothesis of genetic diversity and evolution, the Maximum Genetic Diversity (MGD) hypothesis, to account for the obvious direction towards higher complexity/order during evolution. Huang is a critic of the molecular clock and Neutral theory of molecular evolution and considers the genome to be nearly all functional.
It is based on a pair of self-evident intuitions on construction. The first intuitive idea posits that the maximum tolerable level of random variations/errors/noises in building blocks above atom level is inversely related to system complexity. The equivalent of this concept in biology is that MGD is inversely related to epigenetic complexity. The second intuitive idea posits that any system can allow a certain degree of random noises/errors in its building blocks, and such limited degree of random errors may confer zero, negative, or positive values to the functioning/survival of the system under certain environmental circumstances. In biology, this simply means that an organism has a specific level of MGD and that genetic variations within MGD may confer zero, negative, or positive values to the functioning/survival of the organism under certain environmental circumstances. The first idea describes macroevolution where there is change in complexity over time, while the second idea describes microevolution and population genetics where there is no change in system complexity over time. The second idea thus underlies the proven portions of the modern evolution theory composed of Neo-Darwinism and Kimura’s Neutral theory. The novel points of the MGD hypothesis are 1) macroevolution and microevolution are different, and 2) an increase in organismal or epigenetic complexity is associated with a decrease in MGD. This hypothesis has been supported by numerous observations and has yet to meet a contradiction. It has solved a nearly half century old puzzle of biology, the genetic equidistance phenomenon. By studying fundamental mysteries of common diseases, complex traits, and evolution, our goal is to use the MGD hypothesis to solve major real world biomedical problems and to gain novel insights into the past, present and future of life on Earth.
News:
(Sept 2025) Key development with the maximum genetic diversity theory. It now stands confirmed!
If the strict molecular clock and neutral theory are wrong, then the Maximum Genetic Diversity (MGD) theory must be correct or provides the correct explanation for the genetic equidistance phenomenon. Many may think that falsifying the neutral theory does not automatically validate MGD—but in fact, the logic is decisive. For two sister species derived from a common ancestor, their genetic distance increases over time according to mutation rate and time. If they are equidistant in sequence identity to an outgroup species, and mutation rates are equal, this equidistance could still reflect time-dependent divergence (but not necessarily). However, if mutation rates differ—that is, if the strict molecular clock and neutral theory fail—then the observed equidistance cannot be explained by mutation rates. A distance independent of rate can only reflect a saturation limit: the maximum genetic distance. Thus, explaining genetic equidistance is a strict binary choice: either the strict molecular clock and neutral theory hold, excluding MGD, or they fail, leaving MGD as the only viable explanation. This creates a clear “either-or” relationship. This reasoning is both simple and intuitive, making the inevitability of MGD evident even to non-specialists. In retrospect, it is strikingly straightforward, yet it took seventeen years for me to see it. The strict molecular clock has long been abandoned, replaced by the “relaxed molecular clock,” which undermines the neutral theory, the only premise supporting strict clock predictions. With neutral theory effectively invalid, the MGD theory emerges as the sole remaining explanation for genetic equidistance.