HEPATOCYTE POLYPLOIDY AND METABOLISM LIFE-HISTORY TRAITS - HYPOTHESES TESTING

Two alternate hypotheses explaining the causes of mammalian liver polyploidy have been tested by means of statistical analysis of more than 30 placental species. According to the first (general) hypothesis, the omission of mitosis is beneficial in rapidly growing and differentiating tissues that should early perform their specialized functions (economy on mitosis). In this case it is to be expected that the level of polyploidy is positively correlated to the rate of development. The second hypothesis suggests that hepatocyte polyploidy provides additional gene copies necessary under heavy chemical damage to metabolically active hepatocytes, which have to detoxicate noxious substances. In this case it is reasonable to expect that the level of liver ploidy is positively correlated with the rate of metabolism while inversely with the species lifespan (since it is usually assumed that DNA repair systems are more effective in more long-lived species). It is found that, if taken separately, the developmental rate, the rate of basal metabolism, the body weight (inversely), and the maximum lifespan (inversely) are all correlated with the level of hepatocyte polyploidy. However, all these parameters are intercorrelated. When the other parameters are fixed (in partial correlation analysis), only the developmental rate and the rate of basal metabolism remain significant predictors of the hepatocyte ploidy level, with only the former being a predictor of the nuclear ploidy level, while only the latter being positively correlated with the frequency of binucleated cells. These results suggest that relative importance of the two above explanations can differ for the different modes of liver cell polyploidy. A unifying concept is proposed: polyploidy is a ‘cheap’ way for hepatocytes to cope with toxic insult, evolved particularly in more short- lived r-selected species with rapid development. The most complete dataset of hepatocyte cell and nuclear ploidy levels (with distribution by ploidy classes) in 47 placental mammal species is presented. © 1994 Academic Press. All rights reserved.