, 2006). Being closer to the origin therefore means that intracellular genes (particularly developmental timers) will in general spend more time in a diploid state than intercellular genes during early development. Intracellular www.selleckchem.com/products/azd9291.html genes might therefore be expected to have a higher effective gene dosage during early development, which may relate to their mechanistic role. Alternatively, it is possible that the trends observed are a reflection of different selective pressures/mutational processes occurring at different positions along the genome in relation to the origin. It is

also interesting to note that there are two intercellular pathway genes that lie unusually close to the origin (mbhA and popC), and both of these appear to have entered the myxobacterial lineage through HGT. Excluding mbhA and popC from consideration does increase statistical support for a distinction between intra- and intercellular genes whichever metric is used, although only marginally (for instance, the mean selleck compound severity of the phenotype of intercellular genes would decline from 14±9.8 to 10±6.3). Three separate gene properties (severity of phenotype, degree of sequence conservation and genomic location) vary consistently when genes are categorized according to their role in multicellular development (Fig. 2). In general, intercellular genes are more conserved, more deleterious upon deletion and

further from the origin of replication than genes involved with intracellular signalling. It therefore seems that intercellular genes represent a set of core genes largely essential for multicellular development, whereas intracellular genes constitute a set of accessory genes, which are perhaps subtler in role, and we presume consequently less evolutionarily constrained. Intracellular

genes are conserved in number – there is no evidence of their gain/loss between M. xanthus and S. aurantiaca, suggesting a selective pressure for their retention. However, they are variable and yield subtle phenotypes, implying that they are subject to a weaker selection than intercellular genes. What, then, is the basis of the relative lability of intracellular genes? Perhaps such variability is the genomic signature of genes encoding mutationally robust signalling pathways, which are often Sirolimus cost characterized by genetic redundancy, and minor phenotypes upon deletion (Stelling et al., 2004; Wagner, 2005). However, it is difficult to rationalize why an intracellular signalling pathway would need to be any more robust than an intercellular pathway, especially when the heterogeneous distribution of the cellular population makes intercellular signalling particularly noisy and heterogeneous (Holmes et al., 2010), thus requiring robustness. In general, it would be expected that strains carrying mutations in population genes would be unable to act cooperatively when clonal, and would therefore be unable to form fruits.