The genomics and evolution of inter-sexual mimicry and female-limited polymorphisms in damselflies.

Sex-limited morphs can provide profound insights into the evolution and genomic architecture of complex phenotypes. Inter-sexual mimicry is one particular type of sex-limited polymorphism in which a novel morph resembles the opposite sex. While inter-sexual mimics are known in both sexes and a diverse range of animals, their evolutionary origin is poorly understood. Here, we investigated the genomic basis of female-limited morphs and male mimicry in the common bluetail damselfly. Differential gene expression between morphs has been documented in damselflies, but no causal locus has been previously identified. We found that male mimicry originated in an ancestrally sexually dimorphic lineage in association with multiple structural changes, probably driven by transposable element activity. These changes resulted in ~900 kb of novel genomic content that is partly shared by male mimics in a close relative, indicating that male mimicry is a trans-species polymorphism. More recently, a third morph originated following the translocation of part of the male-mimicry sequence into a genomic position ~3.5 mb apart. We provide evidence of balancing selection maintaining male mimicry, in line with previous field population studies. Our results underscore how structural variants affecting a handful of potentially regulatory genes and morph-specific genes can give rise to novel and complex phenotypic polymorphisms.

The effect of the doublesex gene in body colour masculinization of the damselfly Ischnura senegalensis.

Odonata species display a remarkable diversity of colour patterns, including intrasexual polymorphisms. In the damselfly (Ischnura senegalensis), the expression of a sex-determining transcription factor, the doublesex (Isdsx) gene is reportedly associated with female colour polymorphism (CP) (gynomorph for female-specific colour and andromorph for male-mimicking colour). Here, the function of Isdsx in thoracic coloration was investigated by electroporation-mediated RNA interference (RNAi). RNAi of the Isdsx common region in males and andromorphic females reduced melanization and thus changed the colour pattern into that of gynomorphic females, while the gynomorphic colour pattern was not affected. By contrast, RNAi against the Isdsx long isoform produced no changes, suggesting that the Isdsx short isoform is important for body colour masculinization in both males and andromorphic females. When examining the expression levels of five genes with differences between sexes and female morphs, two melanin-suppressing genes, black and ebony, were expressed at higher levels in the Isdsx RNAi body area than a control area. Therefore, the Isdsx short isoform may induce thoracic colour differentiation by suppressing black and ebony, thereby generating female CP in I. senegalensis. These findings contribute to the understanding of the molecular and evolutionary mechanisms underlying female CP in Odonata.

Candidate genes associated with color morphs of female-limited polymorphisms of the damselfly Ischnura senegalensis.

Many Odonata species exhibit female-limited polymorphisms, where one morph is similar to the conspecific male in body color and other traits (andromorph), whereas one or more other morphs differ from the male (gynomorphs). Here we investigated the differentially expressed transcripts (DETs) among males and two female morph groups (gynomorphs and andromorphs) using RNA-seq to identify candidate transcripts encoding female-limited polymorphisms in the damselfly Ischnura senegalensis. Seven DETs that had significantly different expression levels between males and gynomorphs, but not between males and andromorphs, were identified. The expression levels of four of these candidate genes, doublesex (dsx), black, ebony, and chaoptin (chp), were selected for further analysis using qRT-PCR. Sequence analysis of the dsx amplicons revealed that this gene produced at least three transcripts. Two short transcripts were mainly expressed in males and andromorphs, whereas the long transcript was specifically expressed in both morph female groups; that is, the expression pattern of the dsx splice variants in andromorphs was an intermediate between that of males and gynomorphs. Because the dsx gene functions as a transcription factor that regulates the sex-specific expression of multiple genes, its splice variants in I. senegalensis may explain why the andromorph is female but exhibits some masculinized traits. Because we did not detect different coding sequences of the candidate genes among the different morphs, a diallelic genomic region controlling alternative splicing of dsx, thus determining female-limited polymorphism in I. senegalensis most likely lies in a non-coding region of the dsx gene or in a gene upstream of it.

Suppression of advanced glycation and lipoxidation end products by angiotensin II type-1 receptor blocker candesartan in type 2 diabetic patients with essential hypertension.

OBJECTIVE: This study investigated whether the angiotensin II type-1 receptor blocker (ARB) candesartan affects markers of oxidative stress in type 2 diabetes mellitus (DM) patients with essential hypertension (EH). METHODS: Urinary excretion of pyrraline (PR), pentosidine (PT), acrolein (AC), and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and microalbuminuria were assessed in patients with DM complicated by EH who were treated with candesartan 4 mg/day for 3 months. RESULTS: In a total of 25 patients urinary excretion of PR (nmol/g · cr), PT (pmol/g · cr), and 8-OH-dG (ng/mg · cr) was significantly (all P < 0.05) decreased from (mean ± SEM) 11.9 ± 1.9, 30.6 ± 2.4, and 7.9 ± 0.6, respectively, at baseline to 8.4 ± 1.4, 27.1 ± 2.0, and 6.9 ± 0.6, respectively, at 3 months. Meanwhile, excretion of AC was unaltered from 209.6 ± 40.0 to 189 ± 24.8 nmol/mgcr (P = NS). Urinary albumin excretion was significantly (P < 0.05) reduced from 27.7 ± 4.6 to 14.1 ± 1.1 mg/g · cr. There were weak but statistically significant positive correlations between the change of urinary 8-OH-dG excretion and that of albumin (r = 0.414; P < 0.05) and change of hemoglobin (Hb) A1c (r = 0.45; P < 0.05). CONCLUSION: Candesartan exerts protective effect(s) on the cardiovascular system by suppression of oxidative stress--mainly through inhibiting production of advanced glycation end products (AGEs) rather than of advanced lipoxidation end products (ALEs)--in type 2 DM patients with EH.

Fluvastatin increases bone mineral density in postmenopausal women.

Although several studies have reported a lower risk of osteoporotic fracture in hypercholesterolemic patients (WHO IIa) treated with statin, longitudinal studies on the effects of statins on bone are lacking. The aim of the present study was to evaluate bone mineral density (BMD) and bone turnover changes induced by 3-year fluvastatin treatment in postmenopausal women. Twenty-eight consecutive postmenopausal non-diabetic, normotensive hypercholesterolemic women (64.0±3.6 years) were treated for 36 months with 30 mg/day fluvastatin and 28 non-diabetic, normotensive normocholesterolemic age- and body mass index-matched postmenopausal women served as the control subjects. The result revealed a significant increase of the BMD as compared with the level at the base line (p< 0.001) in the fluvastairn-treated group, from 6 months on ward after the start treatment. Significant differences of the BMD were found between the controls and fluvastatin-treated group (p< 0.001) were at 6, 12, 24 and 36 months after the start of the study. In conclusion our results, although obtained small sample of postmenopausal hypercholesterolemic women, suggest a probable favorable effect of fluvastatin on bone formation and BMD.

High blood pressure, bone-mineral loss and insulin resistance in women.

Increasing evidence indicates that high blood pressure is associated with abnormalities in calcium metabolism. Sustained calcium loss may lead to increased bone-mineral loss in subjects with elevated blood pressure. Furthermore, recent findings indicate a possible linkage between abnormal calcium metabolism and insulin resistance. In the present study, we investigated the relationship(s) among bone-mineral density (BMD), blood pressure, calcium-related and bone metabolic parameters (plasma intact parathyroid hormone (I-PTH), 1,25-dihydroxyvitamin D [1,25(OH)2D], osteocalcin, and urinary deoxypyridinoline), and insulin resistance, as assessed by a conventional homeostasis model (HOMA-R). We compared non-diabetic women with essential hypertension (WHT, n=34) with age-, body mass index- and menopause (yes or no)-matched normotensive, non-diabetic women (WNT, n=34). The BMD for WHT was significantly lower than that for WNT (0.596+/-0.019 vs. 0.666+/-0.024 g/cm2, p<0.05). The BMD was correlated inversely with systolic blood pressure in all subjects examined (r=-0.385, p<0.05). The 24-h urinary calcium/sodium excretion ratio (Ux-Ca/Na) was significantly greater in WHT compared with WNT (p<0.01). In addition, a negative relationship was apparent between Ux-Ca/Na and BMD (r=-0.58, p<0.05). The plasma levels of PTH and 1,25(OH)2D, and HOMA-R were significantly higher in WHT compared with WNT (p<0.01, p<0.05, and p<0.05, respectively), whereas the serum ionized calcium was lower in WHT compared with WNT (p<0.05). There were no significant differences in serum total calcium, inorganic phosphorus, osteocalcin, or urinary deoxypyridinoline between the two groups. These results indicate that high blood pressure is associated with abnormalities in calcium metabolism and insulin resistance in WHT.