Growth arrest-specific (gas) genes are expressed preferentially in cells that enter a quiescent state. gas7, which we identified in serum-starved murine fibroblasts, is reported here to be expressed in vivo selectively in neuronal cells of the mature cerebral cortex, hippocampus, and cerebellum. gas7 transcripts encode a 48-kDa protein containing a structural domain that resembles sequences of OCT2, a POU transcription factor implicated in neuronal development, and synapsins, which have a role in modulating neurotransmitter release. Using in situ hybridization and immunocytochemical analysis, we show that GAS7 expression occurs prominently in cerebellar Purkinje cells and that inhibition of production in terminally differentiating cultures of embryonic murine cerebellum impedes neurite outgrowth from maturing Purkinje cells. Conversely, GAS7 overexpression in undifferentiated neuroblastoma cell cultures dramatically promotes neuritelike outgrowth. Collectively, our results provide evidence for an association between expression of this gas gene and neuronal development.

The swamp type of the Asian water buffalo is assumed to have been domesticated by about 4000 years BP, following the introduction of rice cultivation. Previous localizations of the domestication site were based on mitochondrial DNA (mtDNA) variation within China, accounting only for the maternal lineage. We carried out a comprehensive sampling of China, Taiwan, Vietnam, Laos, Thailand, Nepal and Bangladesh and sequenced the mtDNA Cytochrome b gene and control region and the Y-chromosomal ZFY, SRY and DBY sequences. Swamp buffalo has a higher diversity of both maternal and paternal lineages than river buffalo, with also a remarkable contrast between a weak phylogeographic structure of river buffalo and a strong geographic differentiation of swamp buffalo. The highest diversity of the swamp buffalo maternal lineages was found in south China and north Indochina on both banks of the Mekong River, while the highest diversity in paternal lineages was in the China/Indochina border region. We propose that domestication in this region was later followed by introgressive capture of wild cows west of the Mekong. Migration to the north followed the Yangtze valley as well as a more eastern route, but also involved translocations of both cows and bulls over large distances with a minor influence of river buffaloes in recent decades. Bayesian analyses of various migration models also supported domestication in the China/Indochina border region. Coalescence analysis yielded consistent estimates for the expansion of the major swamp buffalo haplogroups with a credibility interval of 900 to 3900 years BP. The spatial differentiation of mtDNA and Y-chromosomal haplotype distributions indicates a lack of gene flow between established populations that is unprecedented in livestock.

The Lanyu pig is an indigenous breed from Lanyu Islet, located south-east of Taiwan, with phenotypic characteristics distinctive from other pig breeds in Asia and Europe. Based on geographic considerations, the Lanyu pig may have originated from mainland China, Austronesia or the Ryukyu Islands. In the present study, polymorphism of the mitochondrial DNA control region sequence was used to clarify phylogenetic relationships among two herds of Lanyu pigs imported before 1980 from Lanyu Islet into Taiwan and reared in isolation on two different farms. Two distinct mitochondrial control region haplotypes were found. The type I Lanyu sequence appeared independently as a unique clade different from Asian and European pig sequences, while the type II Lanyu sequence was clustered within the major Asian clade. The pairwise distances between the major Asian clade vs. the type I Lanyu and European clades were 0.01726 +/- 0.00275 and 0.01975 +/- 0.00212 changes per site respectively. Estimates of divergence time suggest that the type I Lanyu sequence split from the major Asian pig clade in prehistoric times. The type II Lanyu mtDNA shares a close genetic lineage with Japanese Satsuma and New Zealand Kune Kune mtDNA with pairwise distances of 0.00095 +/- 0.00000 and 0.00192 +/- 0.00000 respectively, indicating gene flow between Lanyu Islet, Japan and Oceania in recent times. Together these results indicate that the type I Lanyu pig has a genetic lineage separate from Asian-type pigs, while the type II Lanyu sequence may represent a more recent introgression of modern Asian pigs.

Gas7, a growth arrest-specific gene originally isolated from serum-starved mouse fibroblast cells, is expressed in vivo predominantly in the brain and is required for neurite formation in cultured mouse cerebellar neurons (Ju et al. [1998] Proc. Natl. Acad. Sci. USA 95: 11423-11428). Here we report that Gas7 plays a key role in the morphological differentiation of PC12 preneuronal rat pheochromocytoma cells (PC12 cells). We found that overexpression of murine Gas7 in PC12 cells leads to an expanded cell morphology and promotes spike-like cell processes that resemble the early stages of neurite formation. These processes undergo elongation upon addition of nerve growth factor (NGF). We also found that the addition of NGF induces the production of endogenous rat-Gas7 (rGas7), which is transiently elevated prior to the appearance of NGF-promoted neurite outgrowths. Furthermore, inhibition of endogenous rGas7 production by antisense nucleotides complimentary to the translation initiation region of a rGas7 cDNA (AJ131902) reduces the NGF-promoted neurite outgrowths. Our results demonstrate that Gas7 by itself influences early cell morphological development and likely functions as an early-stage intermediary in NGF-induced neuronal differentiation of PC12 culture cells.