Comparative genomic investigation of high-elevation adaptation in ectothermic snakes.

Several previous genomic studies have focused on adaptation to high elevations, but these investigations have been largely limited to endotherms. Snakes of the genus Thermophis are endemic to the Tibetan plateau and therefore present an opportunity to study high-elevation adaptations in ectotherms. Here, we report the de novo assembly of the genome of a Tibetan hot-spring snake (Thermophis baileyi) and then compare its genome to the genomes of the other two species of Thermophis, as well as to the genomes of two related species of snakes that occur at lower elevations. We identify 308 putative genes that appear to be under positive selection in Thermophis We also identified genes with shared amino acid replacements in the high-elevation hot-spring snakes compared with snakes and lizards that live at low elevations, including the genes for proteins involved in DNA damage repair (FEN1) and response to hypoxia (EPAS1). Functional assays of the FEN1 alleles reveal that the Thermophis allele is more stable under UV radiation than is the ancestral allele found in low-elevation lizards and snakes. Functional assays of EPAS1 alleles suggest that the Thermophis protein has lower transactivation activity than the low-elevation forms. Our analysis identifies some convergent genetic mechanisms in high-elevation adaptation between endotherms (based on studies of mammals) and ectotherms (based on our studies of Thermophis).

[Role and mechanism of histone deacetylases in mouse neuronal development].

OBJECTIVE: To study the role and mechanism of histone deacetylase 1 (HDAC1) and histone deacetylase 2 (HDAC2) in mouse neuronal development. METHODS: The mice with Synapsin1-Cre recombinase were bred with HDAC1&2flox/flox mice to obtain the mice with neuron-specific HDAC1&2 conditional knockout (knockout group), and their littermates without HDAC1&2 knockout were used as the control group. The general status of the mice was observed and survival curves were plotted. Brain tissue samples were collected from the knockout group and the control group. Western blot and immunohistochemistry were used to measure the protein expression of related neuronal and axonal markers, neuronal nuclear antigen (NeuN), non-phosphorylated neurofilament heavy chain (np-NF200), and phosphorylated neurofilament heavy chain (p-NF200), as well as the downstream effector of the mTOR signaling pathway, phosphorylated S6 ribosomal protein (p-S6). RESULTS: The mice with HDAC1&2 conditional knockout usually died within one month after birth and were significantly smaller than those in the control group, with motor function abnormalities such as tremor and clasping of hindlimbs. Compared with the control group, the knockout group had significant reductions in the protein expression levels of NeuN, np-NF200, p-NF200, and p-S6 (P < 0.05; n=3). CONCLUSIONS: Deletion of HDAC1 and HDAC2 in mouse neurons results in reduced neuronal maturation and axonal dysplasia, which may be associated with the mTOR signaling pathway.