Genes involved in complex adaptive processes tend to have highly conserved upstream regions in mammalian genomes

BACKGROUND:Recent advances in genome sequencing suggest a remarkable conservation in gene content of mammalian organisms. The similarity in gene repertoire present in different organisms has increased interest in studying regulatory mechanisms of gene expression aimed at elucidating the differences in phenotypes. In particular, a proximal promoter region contains a large number of regulatory elements that control the expression of its downstream gene. Although many studies have focused on identification of these elements, a broader picture on the complexity of transcriptional regulation of different biological processes has not been addressed in mammals. The regulatory complexity may strongly correlate with gene function, as different evolutionary forces must act on the regulatory systems under different biological conditions. We investigate this hypothesis by comparing the conservation of promoters upstream of genes classified in different functional categories.RESULTS:By conducting a rank correlation analysis between functional annotation and upstream sequence alignment scores obtained by human-mouse and human-dog comparison, we found a significantly greater conservation of the upstream sequence of genes involved in development, cell communication, neural functions and signaling processes than those involved in more basic processes shared with unicellular organisms such as metabolism and ribosomal function. This observation persists after controlling for G+C content. Considering conservation as a functional signature, we hypothesize a higher density of cis-regulatory elements upstream of genes participating in complex and adaptive processes.CONCLUSION:We identified a class of functions that are associated with either high or low promoter conservation in mammals. We detected a significant tendency that points to complex and adaptive processes were associated with higher promoter conservation, despite the fact that they have emerged relatively recently during evolution. We described and contrasted several hypotheses that provide a deeper insight into how transcriptional complexity might have been emerged during evolution.

On the Emergence of Highly Variable Distributions in the Autonomous System Topology

Recent studies have noted that vertex degree in the autonomous system (AS) graph exhibits a highly variable distribution [15, 22]. The most prominent explanatory model for this phenomenon is the Barabási-Albert (B-A) model [5, 2]. A central feature of the B-A model is preferential connectivity—meaning that the likelihood a new node in a growing graph will connect to an existing node is proportional to the existing node’s degree. In this paper we ask whether a more general explanation than the B-A model, and absent the assumption of preferential connectivity, is consistent with empirical data. We are motivated by two observations: first, AS degree and AS size are highly correlated [11]; and second, highly variable AS size can arise simply through exponential growth. We construct a model incorporating exponential growth in the size of the Internet, and in the number of ASes. We then show via analysis that such a model yields a size distribution exhibiting a power-law tail. In such a model, if an AS’s link formation is roughly proportional to its size, then AS degree will also show high variability. We instantiate such a model with empirically derived estimates of growth rates and show that the resulting degree distribution is in good agreement with that of real AS graphs.