Species differences molecular basis

Molecular phylogeny is a discipline that studies species differences between DNA or protein sequences. Its basic tenet is that during evolution, the sequences have drifted apart by mutation and selection as well as by random drift and fixation of variants in certain positions. The earlier two species separated the more differences became fixed. Phylogenetic trees are constructed on the basis of mutual differences of protein and/or DNA sequence. Comparison of intraspecies variation with between-species variation may in the future yield information on the neutralist/selectionist alternative. McDonald and Kreitman (1991) devised an interesting test against neutrality that compared the ratio of silent/replacement mutation of a given locus within a species with the same ratio between two related species. Under the neutral theory this should be equal (corrected for sample size), but in fact it is not (see Li, 1997, and Hudson, 1993, for a discussion). 

Several lines of investigation have enhanced our understanding of the molecular basis of peroxisome proliferation, with important implications for cancer risk and species differences. In rodent liver, increased organ weight, peroxisome proliferation, increased replicative DNA synthesis and induction of peroxisomal and microsomal fatty... 

Marked species differences in hepatic peroxisome proliferation have been reported (Ashby et al, 1994 lARC, 1995 Lake, 1995a,b Cattley et al, 1998). No study has yet compared the responsiveness of human versus rodent livers in vivo or hepatocytes in vitro to cinnamyl anthranilate however, a growing body of evidence concerning the molecular basis of peroxisome proliferation indicates that human livers and hepatocytes would be refractory to induction of peroxisome proliferation by cinnamyl anthranilate (Doull et al., 1999). 

The nature of other polyol receptor sites and the molecular basis for genetic and species differences in taste capabilities remain largely... 

The electronic configuration of titanium is [Ar] 3d24s2, which means that Ti(IV) compounds are d° species with free coordination sites 1-27,28). H-NMR and 13C-NMR data are known and have been occasionally discussed in terms of bond polarity 19), but such interpretations are obviously of limited value. The electronic structure of methyltitanium trichloride 17 and other reagents have been considered qualitatively 52) and quantitatively S3 56> using molecular orbital procedures. It is problematical to compare these calculations in a quantitative way with those that have been carried out for methyllithium 57> since different methods, basis sets and assumptions are involved, but the extreme polar nature of the C—Li bond does not appear to apply to the C—Ti analog. Several MO calculations of the w-interaction between ethylene and methyltitanium trichloride 17 (models for Ziegler-Natta polymerization) clearly emphasize the role of vacant coordination sites at titanium 58). 

The molecular basis for the evolution of distinct kdr mutations in different insects and arachnids remains unclear. Assuming that the pyrethroid binding site(s) (and/or the pyrethroid response domain) is composed of multiple amino acid residues, there are two ways by which different mutations can be selected in different insects and arachnids. First, the random mutation hypothesis mutation in any pyrethroid binding site/response domain affects pyrethroid toxicity without impacting normal sodium channel functional properties. Thus, selection of different mutations in different insects and arachnids is purely random. Second, the nonrandom mutation hypothesis mutation in any pyrethroid binding site/response domain affects pyrethroid toxicity, but some mutations also drastically alter normal sodium channel functional properties in one species, but not in another, presumably because of different sodium channel backbone sequences. That is, there may be severe fimess costs for some mutations, if placed out of their native protein context. 

LeCluyse EL. Pregnane X receptor molecular basis for species differences in CYP3A induction by xenobiotics. Chem Biol Interact 2001 134 283-9. 

Molecular Basis of Species Differences. In the following section, the properties of PPARa and associated responses in the livers of rodents and primates are compared with an emphasis on human data, if available. The weight of evidence demonstrates that humans respond to PPARa activators differently than rodents in that many of the typical markers of PPARa activator exposure associated with hepatocarcinogenesis in rodents are absent in humans. Differences in the... 

Roberts, R. A. (1999). Peroxisome proliferators mechanisms of adverse effects in rodents and molecular basis for species differences. Arch Toxicol 73, 413—418. 

The experiment provided a molecular basis for explaining the absorption of ChAc to membranes ChAc was found to be a positively charged molecule and was therefore attracted by negatively charged membranes. Species differences in positive surface charge of enzymes explained the species differences observed in membrane affinity (Fig. 1). 

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