Excess amino acid polymorphism in mitochondrial DNA: contrasts among genes from Drosophila, mice, and humans

Recent studies of mitochondrial DNA (mtDNA) variation in mammals and Drosophila have shown an excess of amino acid variation within species (replacement polymorphism) relative to the number of silent and replacement differences fixed between species. To examine further this pattern of nonneutral mtDNA evolution, we present sequence data for the ND3 and ND5 genes from 59 lines of Drosophila melanogaster and 29 lines of D. simulans. Of interest are the frequency spectra of silent and replacement polymorphisms, and potential variation among genes and taxa in the departures from neutral expectations. The Drosophila ND3 and ND5 data show no significant excess of replacement polymorphism using the McDonald-Kreitman test. These data are in contrast to significant departures from neutrality for the ND3 gene in mammals and other genes in Drosophila mtDNA (cytochrome b and ATPase 6). Pooled across genes, however, both Drosophila and human mtDNA show very significant excesses of amino acid polymorphism. Silent polymorphisms at ND5 show a significantly higher variance in frequency than replacement polymorphisms, and the latter show a significant skew toward low frequencies (Tajima's D = -1.954). These patterns are interpreted in light of the nearly neutral theory where mildly deleterious amino acid haplotypes are observed as ephemeral variants within species but do not contribute to divergence. The patterns of polymorphism and divergence at charge-altering amino acid sites are presented for the Drosophila ND5 gene to examine the evolution of functionally distinct mutations. Excess charge-altering polymorphism is observed at the carboxyl terminal and excess charge-altering divergence is detected at the amino terminal. While the mildly deleterious model fits as a net effect in the evolution of nonrecombining mitochondrial genomes, these data suggest that opposing evolutionary pressures may act on different regions of mitochondrial genes and genomes.      

Associations of physical activity with gut microbiota in pre-adolescent children

[Purpose] To determine whether physical activity (PA), primarily the recommended 60 minutes of moderate-to-vigorous PA, is associated with gut bacterial microbiota in 10-year-old children.[Methods] The Block Physical Activity Screener, which provides minutes/day PA variables, was used to determine whether the child met the PA recommendations. 16S rRNA sequencing was performed on stool samples from the children to profile the composition of their gut bacterial microbiota. Differences in alpha diversity metrics (richness, Pielou’s evenness, and Faith’s phylogenetic diversity) by PA were determined using linear regression, whereas beta diversity (unweighted and weighted UniFrac) relationships were assessed using PERMANOVA. Taxon relative abundance differentials were determined using DESeq2.[Results] The analytic sample included 321 children with both PA and 16S rRNA sequencing data (mean age [SD] =10.2 [0.8] years; 54.2% male; 62.9% African American), where 189 (58.9%) met the PA recommendations. After adjusting for covariates, meeting the PA recommendations as well as minutes/day PA variables were not significantly associated with gut richness, evenness, or diversity (p ≥ 0.19). However, meeting the PA recommendations (weighted UniFrac R² = 0.014, p = 0.001) was significantly associated with distinct gut bacterial composition. These compositional differences were partly characterized by increased abundance of Megamonas and Anaerovorax as well as specific Christensenellaceae_R-7_group taxa in children with higher PA.[Conclusion] Children who met the recommendations of PA had altered gut microbiota compositions. Whether this translates to a reduced risk of obesity or associated metabolic diseases is still unclear.     

Gene flow, dispersal, and nested clade analysis among populations of the stonefly Peltoperla tarteri in the southern Appalachians

We examined the genetic structure and phylogeography of populations of the stonefly Peltoperla tarteri in the Southern Appalachians to determine the extent and likely mechanism for dispersal of this stream insect. A 454-base-pair (bp) portion of the mitochondrial control region was sequenced from a minimum of 20 individuals from eight populations. Pairwise FST and exact tests showed high levels of differentiation among almost all populations except those on the same stream. amova analysis detected significant genetic differentiation between streams within drainages (phi(SD) = 0.14, P < 0.001), and there was a slight positive correlation between aquatic distance and genetic distance (r = 0.295, P = 0.03). According to nested clade analysis, the present day pattern of genetic variation in P. tarteri is the result of a historical range expansion coupled with restricted gene flow with isolation by distance. Together, these analyses suggest that adult dispersal is limited and that movement by larvae is the primary dispersal mechanism for P. tarteri.     

The Xmrk oncogene can escape nonfunctionalization in a highly unstable subtelomeric region of the genome of the fish Xiphophorus

The Xmrk oncogene involved in melanoma formation in the fish Xiphophorus was formed relatively recently by duplication of the epidermal growth factor co-orthologue egfrb. In the platyfish X. maculatus, Xmrk is located close to the major sex-determining locus in a subtelomeric region of the X and Y sex chromosomes that frequently undergoes duplications and other rearrangements. This region accumulates repetitive sequences: more than 80% of the 33-kb region 3' of Xmrk is constituted by retrotransposable elements. The high degree of nucleotide identity between X- and Y-linked sequences and the rarity of gonosome-specific rearrangements indicated that the instability observed was not a manifestation of gonosome-specific degeneration. Seven other duplicated genes were found, all corresponding, in contrast to Xmrk, to pseudogenes (nonfunctionalization). Functional persistence of Xmrk in a highly unstable region in divergent Xiphophorus species suggests a beneficial function under certain conditions for this dispensable and potentially injurious gene.     

A novel marker for the platyfish （Xiphophorus maculatus） W chromosome is derived from a Polinton transposon

A consensus sequence,encoding a putative DNA polymerase type B derived from a Polinton transposon,was assembled from the sex determination region of Xiphophorus maculatus.This predicted protein,which is 1,158 as in length,contains a DNA_pol_B_2 domain and a DTDS motif.The DNA polymerase type B gene has about 10 copies in the haploid X.maculatus genome with one Y-specific copy.Interestingly,it has specific copies on the W chromosome in the X.maculatus Usumacinta strain (sex determination with female heterogamety),which represent new markers for this type of sex chromosome in platyfish.This marker with W-and Y-specific copies suggests relationship between different types of gonosomes and allows comparing male and female heterogameties in the platyfish.Further molecular analysis of the DNA polymerase type B gene in X.maculatus will shed new light on the evolution of sex chromosomes in platyfish.     

Blood pressure maintenance in NHE3-deficient mice with transgenic expression of NHE3 in small intestine

NHE3 Na(+)/H(+) exchanger knockout (Nhe3(-/-)) mice have severe absorptive deficits in the kidney proximal tubule and intestinal tract. The resulting hypovolemia has confounded efforts to carefully evaluate the specific effects of NHE3 deficiency on kidney function. Development of mice with transgenic expression of NHE3 in the small intestine (tgNhe3(-/-)) has allowed us to analyze the role of renal NHE3 in overall maintenance of blood pressure, pressure natriuresis, and autoregulation of both glomerular filtration rate (GFR) and renal blood flow (RBF). Ambulatory blood pressure, measured by telemetry, was lower in tgNhe3(-/-) mice than in wild-type controls (tgNhe3(+/+)) when the mice were maintained on a normal NaCl diet but was normalized when they were provided with a high NaCl intake. Furthermore, administration of the AT1-receptor blocker losartan showed that circulating ANG II plays a major role in maintaining blood pressure in tgNhe3(-/-) mice fed normal NaCl but not in those receiving high NaCl. Clearance studies revealed a blunted pressure-natriuresis response in tgNhe3(-/-) mice at lower blood pressures but a robust response at higher blood pressures. Autoregulation of GFR and RBF was normal in tgNhe3(-/-) mice. These results show that dietary NaCl loading normalizes blood pressure in awake tgNhe3(-/-) mice and that alterations in NHE3 activity are not essential for normal autoregulation of GFR and RBF. Furthermore, the data strongly support the hypothesis that NHE3 plays an important role in the diuretic and natriuretic responses to increases in blood pressure but also show that mechanisms not involving NHE3 mediate pressure natriuresis in the higher range of blood pressures studied.