While the majority of DNA in eukaryotes is in the nucleus, a small but functionally significant amount is found in organelles such as chloroplasts and mitochondria. A recent, rather remarkable, finding has been that in vertebrates the DNA in the mitochondria (mtDNA) is evolving 5-10 times faster than the DNA in the nucleus. No similar studies have been done with invertebrates. Using the technique of DNADNA hybridization, we have measured the degree of nucleotide substitution between Drosophila melanogaster and Drosophila yakuba for both single-copy nuclear DNA (scnDNA) and mtDNA. The change in melting temperature is the same in both types of DNA hybrids. Thus we conclude that mtDNA and scnDNA are evolving at similar rates in these Drosophila. Considerable DNA sequence data are available for the mtDNAs studied, allowing us to estimate that a PC change in melting temperature corresponds to a 1.5-2% base-pair mismatch.In all metazoans that have been studied, the size and content of mitochondrial DNA (mtDNA) are remarkably similar. The mtDNA molecule is between 15,000 and 20,000 base pairs and codes for 13 polypeptides, two ribosomal RNAs, and several tRNAs (1, 2). Because of their relatively small size and ease of purification, mtDNAs have been well characterized in a number of species, and for some of them the complete nucleotide sequences have been determined (3-6). One of the more remarkable findings from an evolutionary viewpoint is that mtDNA accumulates nucleotide substitutions 5-10 times more rapidly than does nuclear DNA (7-9). Virtually all the data indicating the rapid rate of evolution of mtDNA compared to nuclear DNA have come from vertebrates. We report here a direct study of the relative rates of evolution of these two types of DNA in an invertebrate (Drosophila), and we conclude that they are not evolving at significantly different rates.Drosophila melanogaster and Drosophila yakuba are closely related sibling species in the melanogaster subgroup (10). The complete nucleotide sequence has been determined for D. yakuba mtDNA (6, 11), and about 30% of the sequence has been determined for D. melanogaster mtDNA (12). For the region that is known in both species, the sequences differ at 7.2% of the nucleotide positions (11). Less is known about the divergence of nuclear DNA between these two species. Limited isozyme data exist (13), as do sequence data for the alcohol dehydrogenase locus for related taxa (14), although neither of these sources allows a thorough or direct measure of overall nuclear DNA divergence between D. melanogaster and D. yakuba. A direct and convenient method to determine overall sequence divergence of nuclear genomes is DNA-DNA hybridization (15-17). We report here the results of DNADNA hybridization studies of both the mtDNA and single-copy nuclear DNA (scnDNA) in D. melanogaster and D. yakuba.The technique of DNA-DNA hybridization relies on the fact that double-stranded DNA becomes single-stranded when heated. The temperature at which the strands separate is determined by ...

BackgroundAlthough vitamin D receptor (VDR) polymorphisms have been shown to be associated with abnormal glucose metabolism, the reported polymorphisms are unlikely to have any biological consequences. The VDR gene has two potential translation initiation sites. A T-to-C polymorphism has been noted in the first ATG (f allele), abolishing the first translation initiation site and resulting in a peptide lacking the first three amino acids (F allele). We examined the role of this polymorphism in insulin sensitivity and beta cell function. This study included 49 healthy Caucasian subjects (28 females, age 28 ± 1 years old, body mass index 24.57 ± 0.57 kg/m2, waist-hip ratio 0.81 ± 0.01 cm/cm). They were all normotensive (less than 140/90 mmHg) and glucose tolerant, which was determined by a standard 75-gm oral glucose tolerance test. Their beta cell function (%B) and insulin sensitivity (%S) were calculated based on the Homeostasis Model Assessment (HOMA). Their genotypes were determined by a polymerase chain reaction-restriction fragment length polymorphism analysis. Phenotypes were compared between genotypic groups.ResultsThere were 18 FF, 21 Ff, and 10 ff subjects. Since only 10 ff subjects were identified, they were pooled with the Ff subjects during analyses. The FF and Ff/ff groups had similar glucose levels at each time point before and after a glucose challenge. The Ff/ff group had higher insulin levels than the FF group at fasting (P=0.006), 30 minutes (P=0.009), 60 minutes (P=0.049), and 90 minutes (P=0.042). Furthermore, the Ff/ff group also had a larger insulin area under the curve than the FF group (P=0.009). While no difference was noted in %B, the Ff/ff group had a lower %S than the FF group (0.53 vs. 0.78, P=0.006). A stepwise regression analysis confirmed that the Fok I polymorphism was an independent determinant for %S, accounting for 29.3% of variation in %S when combined with waist-hip ratio.ConclusionsWe report that the Fok I polymorphism at the VDR gene locus is associated with insulin sensitivity, but has no influence on beta cell function in healthy Caucasians. Although this polymorphism has been shown to affect the activation of vitamin D-dependent transcription, the molecular basis of the association between this polymorphism and insulin resistance remains to be determined.

We demonstrated that the A54T polymorphism at the FABP2 locus is a risk factor for insulin resistance in a Caucasian population.

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