Bactrian camel (Camelus bactrianus), dromedary (Camelus dromedarius) and alpaca (Vicugna pacos) are economically important livestock. Although the Bactrian camel and dromedary are large, typically arid-desert-adapted mammals, alpacas are adapted to plateaus. Here we present high-quality genome sequences of these three species. Our analysis reveals the demographic history of these species since the Tortonian Stage of the Miocene and uncovers a striking correlation between large fluctuations in population size and geological time boundaries. Comparative genomic analysis reveals complex features related to desert adaptations, including fat and water metabolism, stress responses to heat, aridity, intense ultraviolet radiation and choking dust. Transcriptomic analysis of Bactrian camels further reveals unique osmoregulation, osmoprotection and compensatory mechanisms for water reservation underpinned by high blood glucose levels. We hypothesize that these physiological mechanisms represent kidney evolutionary adaptations to the desert environment. This study advances our understanding of camelid evolution and the adaptation of camels to arid-desert environments.

Although the cold-shock response has now been studied in a number of different organisms for several decades, it is only in the last few years that we have begun to understand the molecular mechanisms that govern adaptation to cold stress. Notably, all organisms from prokaryotes to plants and higher eukaryotes respond to cold shock in a comparatively similar manner. The general response of cells to cold stress is the elite and rapid overexpression of a small group of proteins, the so-called CSPs (cold-shock proteins). The most well characterized CSP is CspA, the major CSP expressed in Escherichia coli upon temperature downshift. More recently, a number of reports have shown that exposing yeast or mammalian cells to sub-physiological temperatures (<30 or <37 degrees C respectively) invokes a co-ordinated cellular response involving modulation of transcription, translation, metabolism, the cell cycle and the cell cytoskeleton. In the present review, we summarize the regulation and role of cold-shock genes and proteins in the adaptive response upon decreased temperature with particular reference to yeast and in vitro cultured mammalian cells. Finally, we present an integrated model for the co-ordinated responses required to maintain the viability and integrity of mammalian cells upon mild hypothermic cold shock.

There are a growing number of reports on the sub-physiological temperature culturing (<37 degrees C) of mammalian cells for increased recombinant protein yield, although the effect is variable between cell lines, expression systems, and the product of interest. What is becoming clear is that exposing mammalian cells to sub-physiological temperatures invokes a coordinated cellular response involving modulation of the cell cycle, metabolism, transcription, translation, and the cell cytoskeleton. Opportunities currently exist for further enhancement of the cold-shock effect on recombinant protein production in mammalian cells through advancements in our understanding of the mechanisms involved in the cold-shock response.

Cold-inducible RNA binding protein (CIRP) is a mammalian protein whose expression is up-regulated in response to mild hypothermia. Although the exact function of this protein is currently unknown, it is thought to function as an RNA chaperone, facilitating mRNA translation upon the perception of cold stress. In this study we have identified and characterized the major CIRP 59-untranslated region (59-UTR) transcripts in mouse embryonic fibroblast NIH-3T3 cells. We show that the 59-UTR of CIRP, a protein highly homologous to the cold-shock protein Rbm3, is much shorter than the previously published 59 leader sequence of Rbm3. In addition, three major CIRP transcripts with different transcription start sites are generated, with the levels of each of these transcripts being regulated in response to time and temperature. The major transcript generated at 37°C does not encode for the full-length CIRP open reading frame, while the two major transcripts at 32°C do. Further, the longest transcript detected at 32°C shows a discrete expression and stability profile under mild hypothermic conditions and exhibits internal ribosome entry segment (IRES)-like activity. The IRES-like activity is not responsive to conditions of mild hypothermia or hypoxia, but the levels and stability of the transcript harboring the putative IRES are increased at 32°C. We discuss the emerging transcriptional and translational mechanisms by which CIRP expression appears to be controlled and the role that the 59-UTR plays in the modulation of CIRP expression.