Sympatric speciation (SS), i.e., speciation within a freely breeding population or in contiguous populations, was first proposed by Darwin [Darwin C (1859) On the Origins of Species by Means of Natural Selection] and is still controversial despite theoretical support [Gavrilets S (2004) Fitness Landscapes and the Origin of Species (MPB-41)] and mounting empirical evidence. Speciation of subterranean mammals generally, including the genus Spalax, was considered hitherto allopatric, whereby new species arise primarily through geographic isolation. Here we show in Spalax a case of genome-wide divergence analysis in mammals, demonstrating that SS in continuous populations, with gene flow, encompasses multiple widespread genomic adaptive complexes, associated with the sharply divergent ecologies. The two abutting soil populations of S. galili in northern Israel habituate the ancestral Senonian chalk population and abutting derivative Plio-Pleistocene basalt population. Population divergence originated ∼0.2–0.4 Mya based on both nuclear and mitochondrial genome analyses. Population structure analysis displayed two distinctly divergent clusters of chalk and basalt populations. Natural selection has acted on 300+ genes across the genome, diverging Spalax chalk and basalt soil populations. Gene ontology enrichment analysis highlights strong but differential soil population adaptive complexes: in basalt, sensory perception, musculature, metabolism, and energetics, and in chalk, nutrition and neurogenetics are outstanding. Population differentiation of chemoreceptor genes suggests intersoil population's mate and habitat choice substantiating SS. Importantly, distinctions in protein degradation may also contribute to SS. Natural selection and natural genetic engineering [Shapiro JA (2011) Evolution: A View From the 21st Century] overrule gene flow, evolving divergent ecological adaptive complexes. Sharp ecological divergences abound in nature; therefore, SS appears to be an important mode of speciation as first envisaged by Darwin [Darwin C (1859) On the Origins of Species by Means of Natural Selection].

Aging is often perceived as a degenerative process caused by random accrual of cellular damage over time. In spite of this, age can be accurately estimated by epigenetic clocks based on DNA methylation profiles from almost any tissue of the body. Since such pan-tissue epigenetic clocks have been successfully developed for several different species, it is difficult to ignore the likelihood that a defined and shared mechanism instead, underlies the aging process. To address this, we generated 10,000 methylation arrays, each profiling up to 37,000 cytosines in highly-conserved stretches of DNA, from over 59 tissue-types derived from 128 mammalian species. From these, we identified and characterized specific cytosines, whose methylation levels change with age across mammalian species. Genes associated with these cytosines are greatly enriched in mammalian developmental processes and implicated in age-associated diseases. From the methylation profiles of these age-related cytosines, we successfully constructed three highly accurate universal mammalian clocks for eutherians, and one universal clock for marsupials. The universal clocks for eutherians are similarly accurate for estimating ages (r>0.96) of any mammalian species and tissue with a single mathematical formula. Collectively, these new observations support the notion that aging is indeed evolutionarily conserved and coupled to developmental processes across all mammalian species - a notion that was long-debated without the benefit of this new and compelling evidence.

The aim of this study was to explore a new way of treating drug addiction by ablating the nucleus accumbens (NA_C), which has a close relationship with drug-induced psychological dependence, using stereotactic surgery, blocking the mesocorticolimbic dopamine circuit, alleviating craving for drugs and lowering the relapse rate after detoxification. On the basis of animal experiments, stereotactic surgery was performed in 28 patients by making a lesion in the NA_C bilaterally to treat opiate drug dependence. Indications, the criterion of therapeutic effect, treatment process and the therapeutic and safety evaluation index of the surgery were formulated particularly. The mean follow-up period was 15 months. Relapse has not occurred in 11 cases up till now. Drug-free time in these patients has been more than half a year in 4 cases (more than a year in 3 cases), and less than half a year in 7 cases. Relapse occurred in 15 cases after surgery. Drug-free time in these patients was more than half a year in 3 cases, between 1 month and half a year in 10 cases and less than 1 month in 2 cases. The therapeutic effect was excellent in 7 cases (26.9%), good in 10 cases (38.5%) and poor in 2 cases (7.7%). Another 7 cases were still under investigation at the time of writing. Relapse rates after surgery were 7.7, 38.5 and 57.5% within 1 month, between 1 month and half a year and after more than half a year, respectively. There were no common complications of surgery such as intracranial hematoma or infection in these patients after operation. Character type was changed slightly in 2 cases, and 4 cases suffered temporary memory loss, which did not affect their daily lives and learning function. They all recovered within 1 month. There were different degrees of effectiveness of treating drug addicts’ psychological dependence by making lesions in the NA_C bilaterally with stereotactic surgery. No particular complications occurred. The operation is safe and feasible. The mean follow-up time in this study was 15 months. The effectiveness was satisfactory. The relapse rate of drug addicts after detoxification was clearly reduced.

Inorganic phosphate (Pi) transporters (PTs) play vital roles in Pi uptake and translocation in plants. Under Pi sufficient conditions, PTs are degraded to prevent excess Pi accumulation. The mechanisms targeting PTs for degradation are not fully elucidated. In this study, we found that the Oryza sativa (rice) ortholog of Arabidopsis thaliana nitrogen limitation adaptation (NLA), OsNLA1 protein, a RING-type E3 ubiquitin-ligase, was predominantly localized in the plasma membrane, and could interact with rice phosphate transporters OsPT2 and OsPT8. Mutation of the 265th cysteine residue in OsNLA1 that was required for ubiquitination prevented breakdown of OsPT2/PT8, suggesting OsNLA1 targeted OsPT2/PT8 for degradation. Mutation in OsNLA1 (osnla1) led to a significant increase of Pi concentration in leaves in a nitrate-independent manner. Overexpression of OsNLA1 or repression of OsPT2/PT8 restored the high leaf Pi concentration in osnla1 mutants to a level similar to that of wild-type plants. In contrast to what has been observed in Arabidopsis, the transcript abundance of OsNLA1 did not decrease under Pi limited conditions or in OsmiR827 (microRNA827)- or OsPHR2 (PHOSPHATE STARVATION RESPONSE 2)-overexpressing transgenic lines. Moreover, there was no interaction of OsNLA1 and OsPHO2, an E2 ubiquitin-conjugase, suggesting that OsPHO2 was not the partner of OsNLA1 involved in ubiquitin-mediated PT degradation. Our results show that OsNLA1 is involved in maintaining phosphate homeostasis in rice by mediating the degradation of OsPT2 and OsPT8, and OsNLA1 differs from the ortholog in Arabidopsis in several aspects.

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