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Abstract Chromosome-scale genome assemblies based on ultralong-read sequencing technologies are able to illuminate previously intractable aspects of genome biology such as fine-scale centromere structure and large-scale variation in genome features such as heterochromatin, GC content, recombination rate, and gene content. We present here a new chromosome-scale genome of the Mongolian gerbil (Meriones unguiculatus), which includes the complete sequence of all centromeres. Gerbils are thus the one of the first vertebrates to have their centromeres completely sequenced. Gerbil centromeres are composed of four different repeats of length 6, 37, 127, or 1,747 bp, which occur in simple alternating arrays and span 1–6 Mb. Gerbil genomes have both an extensive set of GC-rich genes and chromosomes strikingly enriched for constitutive heterochromatin. We sought to determine if there was a link between these two phenomena and found that the two heterochromatic chromosomes of the Mongolian gerbil have distinct underpinnings: Chromosome 5 has a large block of intraarm heterochromatin as the result of a massive expansion of centromeric repeats, while chromosome 13 is comprised of extremely large (>150 kb) repeated sequences. In addition to characterizing centromeres, our results demonstrate the importance of including karyotypic features such as chromosome number and the locations of centromeres in the interpretation of genome sequence data and highlight novel patterns involved in the evolution of chromosomes.

There are two main factors explaining variation among species and the evolution of characters along phylogeny: adaptive change, including phenotypic and genetic responses to selective pressures, and phylogenetic inertia, or the resemblance between species due to shared phylogenetic history. Phenotype-habitat colour match, a classic Darwinian example of the evolution of camouflage (crypsis), offers the opportunity to test the importance of historical versus ecological mechanisms in shaping phenotypes among phylogenetically closely related taxa. To assess it, we investigated fur (phenotypic data) and habitat (remote sensing data) colourations, along with phylogenetic information, in the species-rich Gerbillus genus. Overall, we found a strong phenotype-habitat match, once the phylogenetic signal is taken into account. We found that camouflage has been acquired and lost repeatedly in the course of the evolutionary history of Gerbillus . Our results suggest that fur colouration and its covariation with habitat is a relatively labile character in mammals, potentially responding quickly to selection. Relatively unconstrained and substantial genetic basis, as well as structural and functional independence from other fitness traits of mammalian colouration might be responsible for that observation.

Recombination increases the local GC-content in genomic regions through GC-biased gene conversion (gBGC). The recent discovery of a large genomic region with extreme GC-content in the fat sand rat Psammomys obesus provides a model to study the effects of gBGC on chromosome evolution. Here, we compare the GC-content and GC-to-AT substitution patterns across protein-coding genes of four gerbil species and two murine rodents (mouse and rat). We find that the known high-GC region is present in all the gerbils, and is characterized by high substitution rates for all mutational categories (AT-to-GC, GC-to-AT, and GC-conservative) both at synonymous and nonsynonymous sites. A higher AT-to-GC than GC-to-AT rate is consistent with the high GC-content. Additionally, we find more than 300 genes outside the known region with outlying values of AT-to-GC synonymous substitution rates in gerbils. Of these, over 30% are organized into at least 17 large clusters observable at the megabase-scale. The unusual GC-skewed substitution pattern suggests the evolution of genomic regions with very high recombination rates in the gerbil lineage, which can lead to a runaway increase in GC-content. Our results imply that rapid evolution of GC-content is possible in mammals, with gerbil species providing a powerful model to study the mechanisms of gBGC.

It has been studied that the damage or death of neurons in the hippocampus is different according to hippocampal subregions, cornu ammonis 1–3 (CA1–3), after transient ischemia in the forebrain, showing that pyramidal neurons located in the subfield CA1 (CA1) are most vulnerable to this ischemia. Hyperthermia is a proven risk factor for brain ischemia and can develop more severe and extensive brain damage related with mortality rate. It is well known that heme oxygenase-1 (HO-1) activity and expression is increased by various stimuli in the brain, including hyperthermia. HO-1 can be either protective or deleterious in the central nervous system, and its roles depend on the expression levels of enzymes. In this study, we investigated the effects of hyperthermia during ischemia on HO-1 expression and neuronal damage/death in the hippocampus to examine the relationship between HO-1 and neuronal damage/death following 5-min transient ischemia in the forebrain using gerbils. Gerbils were assigned to four groups: (1) sham-operated gerbils with normothermia (Normo + sham group); (2) ischemia-operated gerbils with normothermia (Normo + ischemia group); (3) sham-operated gerbils with hyperthermia (39.5 ± 0.2 °C) during ischemia (Hyper + sham group); and (4) ischemia-operated gerbils with hyperthermia during ischemia (Hyper + ischemia group). HO-1 expression levels in CA1–3 of the Hyper + ischemia group were significantly higher than those in the Normo + ischemia group. HO-1 immunoreactivity in the Hyper + ischemia group was significantly increased in pyramidal neurons and astrocytes with time after ischemia, and the immunoreactivity was significantly higher than that in the Normo + ischemia group. In the Normo + Ischemia group, neuronal death was shown in pyramidal neurons located only in CA1 at 5 days after ischemia. However, in the Hyper + ischemia group, pyramidal neuronal death occurred in CA1–3 at 2 days after ischemia. Taken together, our findings showed that brain ischemic insult during hyperthermic condition brings up earlier and severer neuronal damage/death in the hippocampus, showing that HO-1 expression in neurons and astrocytes is different according to brain subregions and temperature condition. Based on these findings, we suggest that hyperthermia in patients with ischemic stroke must be taken into the consideration in the therapy.

Several processes can lead to strong GC skew in localized genomic regions. In most cases, GC skew should not affect conserved amino acids because natural selection will purge deleterious alleles. However, in the gerbil subfamily of rodents, several conserved genes have undergone radical alteration in association with strong GC skew. An extreme example concerns the highly conserved homeobox gene Pdx1, which is uniquely divergent and GC rich in the sand rat Psammomys obesus and close relatives. Here, we investigate the antagonistic interplay between very rare amino acid changes driven by GC skew and the force of natural selection. Using ectopic protein expression in cell culture, pulse-chase labeling, in vitro mutagenesis, and drug treatment, we compare properties of mouse and sand rat Pdx1 proteins. We find that amino acid change driven by GC skew resulted in altered protein stability, with a significantly longer protein half-life for sand rat Pdx1. Using a reversible inhibitor of the 26S proteasome, MG132, we find that sand rat and mouse Pdx1 are both degraded through the ubiquitin proteasome pathway. However, in vitro mutagenesis reveals this pathway operates through different amino acid residues. We propose that GC skew caused loss of a key ubiquitination site, conserved through vertebrate evolution, and that sand rat Pdx1 evolved or fixed a new ubiquitination site to compensate. Our results give molecular insight into the power of natural selection in the face of maladaptive changes driven by strong GC skew.

The sand rat Psammomys obesus is a gerbil species native to deserts of North Africa and the Middle East, and is constrained in its ecology because high carbohydrate diets induce obesity and type II diabetes that, in extreme cases, can lead to pancreatic failure and death. We report the sequencing of the sand rat genome and discovery of an unusual, extensive, and mutationally biased GC-rich genomic domain. This highly divergent genomic region encompasses several functionally essential genes, and spans the ParaHox cluster which includes the insulin-regulating homeobox gene Pdx1. The sequence of sand rat Pdx1 has been grossly affected by GC-biased mutation, leading to the highest divergence observed for this gene across the Bilateria. In addition to genomic insights into restricted caloric intake in a desert species, the discovery of a localized chromosomal region subject to elevated mutation suggests that mutational heterogeneity within genomes could influence the course of evolution.

We investigated the effects of pyridoxine deficiency on ischemic neuronal death in the hippocampus of gerbil (n = 5 per group). Serum pyridoxal 5′-phosphate levels were significantly decreased in Pyridoxine-deficient diet (PDD)-fed gerbils, while homocysteine levels were significantly increased in sham- and ischemia-operated gerbils. PDD-fed gerbil showed a reduction in neuronal nuclei (NeuN)-immunoreactive neurons in the medial part of the hippocampal CA1 region three days after. Reactive astrocytosis and microgliosis were found in PDD-fed gerbils, and transient ischemia caused the aggregation of activated microglia in the stratum pyramidale three days after ischemia. Lipid peroxidation was prominently increased in the hippocampus and was significantly higher in PDD-fed gerbils than in Control diet (CD)-fed gerbils after ischemia. In contrast, pyridoxine deficiency decreased the proliferating cells and neuroblasts in the dentate gyrus in sham- and ischemia-operated gerbils. Nuclear factor erythroid-2-related factor 2 (Nrf2) and brain-derived neurotrophic factor (BDNF) levels also significantly decreased in PDD-fed gerbils sham 24 h after ischemia. These results suggest that pyridoxine deficiency accelerates neuronal death by increasing serum homocysteine levels and lipid peroxidation, and by decreasing Nrf2 levels in the hippocampus. Additionally, it reduces the regenerated potentials in hippocampus by decreasing BDNF levels. Collectively, pyridoxine is an essential element in modulating cell death and hippocampal neurogenesis after ischemia.

Astaxanthin is a powerful biological antioxidant and is naturally generated in a great variety of living organisms. Some studies have demonstrated the neuroprotective effects of ATX against ischemic brain injury in experimental animals. However, it is still unknown whether astaxanthin displays neuroprotective effects against severe ischemic brain injury induced by longer (severe) transient ischemia in the forebrain. The purpose of this study was to evaluate the neuroprotective effects of astaxanthin and its antioxidant activity in the hippocampus of gerbils subjected to 15-min transient forebrain ischemia, which led to the massive loss (death) of pyramidal cells located in hippocampal cornu Ammonis 1-3 (CA1-3) subfields. Astaxanthin (100 mg/kg) was administered once daily for three days before the induction of transient ischemia. Treatment with astaxanthin significantly attenuated the ischemia-induced loss of pyramidal cells in CA1-3. In addition, treatment with astaxanthin significantly reduced ischemia-induced oxidative DNA damage and lipid peroxidation in CA1-3 pyramidal cells. Moreover, the expression of the antioxidant enzymes superoxide dismutase (SOD1 and SOD2) in CA1-3 pyramidal cells were gradually and significantly reduced after ischemia. However, in astaxanthin-treated gerbils, the expression of SOD1 and SOD2 was significantly high compared to in-vehicle-treated gerbils before and after ischemia induction. Collectively, these findings indicate that pretreatment with astaxanthin could attenuate severe ischemic brain injury induced by 15-min transient forebrain ischemia, which may be closely associated with the decrease in oxidative stress due to astaxanthin pretreatment.

17α-Ethinylestradiol is an endocrine-disrupting chemical that make up most contraceptive pills and can be found in the environment. Exposure to ethinylestradiol in different development periods may promote changes in morphophysiological parameters of reproductive and endocrine organs. Considering that the effects of low doses (15 µg/kg/day) of ethinylestradiol in ovaries from 12-month-old female gerbils (Meriones unguiculatus) were investigated. Four experimental groups used were control (without treatment), EE/PRE (treated from the 18th to the 22nd gestational day), EE/PUB (treated from the 42nd to the 49th day of life), and EE/PRE-PUB (treated in the both periods). The animals were euthanized at 12 months. Testosterone and 17β-estradiol levels were measured. The ovaries were stained with Hematoxylin and Eosin, Periodic Acid Schiff, and Gomori’s Trichome. The follicles, corpus luteum, interstitial gland, lipofuscin, ovarian epithelium, and tunica albuginea were analyzed. Estradiol was higher in EE/PRE and EE/PUB groups, while testosterone was higher only in EE/PUB group. The main changes in follicle count occurred in EE/PUB and EE/PRE-PUB groups, with higher primordial follicle count and lower maturation of follicles. The corpus luteum was more evident in EE/PRE group. No differences were found in atretic follicles count. A higher area occupied by interstitial gland cells and lipofuscin deposit in these cells was noted in EE/PUB and EE/PRE-PUB groups. Higher epithelium height and thicker tunic albuginea were showed in treated groups. These results suggest that exposure to doses of EE2 in prenatal and pubertal periods of the development leads to morphological changes in senile ovaries.

Nonmodel rodents are widely used as subjects for both basic and applied biological research, but the genetic diversity of the study individuals is rarely quantified. University-housed colonies tend to be small and subject to founder effects and genetic drift; so they may be highly inbred or show substantial genetic divergence from other colonies, even those derived from the same source. Disregard for the levels of genetic diversity in an animal colony may result in a failure to replicate results if a different colony is used to repeat an experiment, as different colonies may have fixed alternative variants. Here we use high throughput sequencing to demonstrate genetic divergence in three isolated colonies of Mongolian gerbil (Meriones unguiculatus) even though they were all established recently from the same source. We also show that genetic diversity in allegedly “outbred” colonies of nonmodel rodents (gerbils, hamsters, house mice, deer mice, and rats) varies considerably from nearly no segregating diversity to very high levels of polymorphism. We conclude that genetic divergence in isolated colonies may play an important role in the “replication crisis.” In a more positive light, divergent rodent colonies represent an opportunity to leverage genetically distinct individuals in genetic crossing experiments. In sum, awareness of the genetic diversity of an animal colony is paramount as it allows researchers to properly replicate experiments and also to capitalize on other genetically distinct individuals to explore the genetic basis of a trait.