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Forces shaping a Hox morphogenetic gene network.

ABSTRACT: The Abdominal-B selector protein induces organogenesis of the posterior spiracles by coordinating an organ-specific gene network. The complexity of this network begs the questions of how it originated and what selective pressures drove its formation. Given that the network likely formed in a piecemeal fashion, with elements recruited sequentially, we studied the consequences of expressing individual effectors of this network in naive epithelial cells. We found that, with exception of the Crossveinless-c (Cv-c) Rho GTPase-activating protein, most effectors exert little morphogenetic effect by themselves. In contrast, Cv-c expression causes cell motility and down-regulates epithelial polarity and cell adhesion proteins. These effects differ in cells endogenously expressing Cv-c, which have acquired compensatory mechanisms. In spiracle cells, the down-regulation of polarity and E-cadherin expression caused by Cv-c-induced Rho1 inactivation are compensated for by the simultaneous spiracle up-regulation of guanine nucleotide exchange factor (GEF) proteins, cell polarity, and adhesion molecules. Other epithelial cells that have coopted Cv-c to their morphogenetic gene networks are also resistant to Cv-c's deleterious effects. We propose that cooption of a novel morphogenetic regulator to a selector cascade causes cellular instability, resulting in strong selective pressure that leads that same cascade to recruit molecules that compensate it. This experimental-based hypothesis proposes how the frequently observed complex organogenetic gene networks are put together.

SUBMITTER: Sotillos S

PROVIDER: S-EPMC3600447 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Forces shaping a Hox morphogenetic gene network.

Sotillos Sol S Aguilar Mario M Hombría James Castelli-Gair JC

Proceedings of the National Academy of Sciences of the United States of America 20130225 11

The Abdominal-B selector protein induces organogenesis of the posterior spiracles by coordinating an organ-specific gene network. The complexity of this network begs the questions of how it originated and what selective pressures drove its formation. Given that the network likely formed in a piecemeal fashion, with elements recruited sequentially, we studied the consequences of expressing individual effectors of this network in naive epithelial cells. We found that, with exception of the Crossve ...[more]

PMID: 23440219

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Project description:BACKGROUND: Levels of differentiation among populations depend both on demographic and selective factors: genetic drift and local adaptation increase population differentiation, which is eroded by gene flow and balancing selection. We describe here the genomic distribution and the properties of genomic regions with unusually high and low levels of population differentiation in humans to assess the influence of selective and neutral processes on human genetic structure. METHODS: Individual SNPs of the Human Genome Diversity Panel (HGDP) showing significantly high or low levels of population differentiation were detected under a hierarchical-island model (HIM). A Hidden Markov Model allowed us to detect genomic regions or islands of high or low population differentiation. RESULTS: Under the HIM, only 1.5% of all SNPs are significant at the 1% level, but their genomic spatial distribution is significantly non-random. We find evidence that local adaptation shaped high-differentiation islands, as they are enriched for non-synonymous SNPs and overlap with previously identified candidate regions for positive selection. Moreover there is a negative relationship between the size of islands and recombination rate, which is stronger for islands overlapping with genes. Gene ontology analysis supports the role of diet as a major selective pressure in those highly differentiated islands. Low-differentiation islands are also enriched for non-synonymous SNPs, and contain an overly high proportion of genes belonging to the 'Oncogenesis' biological process. CONCLUSIONS: Even though selection seems to be acting in shaping islands of high population differentiation, neutral demographic processes might have promoted the appearance of some genomic islands since i) as much as 20% of islands are in non-genic regions ii) these non-genic islands are on average two times shorter than genic islands, suggesting a more rapid erosion by recombination, and iii) most loci are strongly differentiated between Africans and non-Africans, a result consistent with known human demographic history.

Dataset Information

Forces shaping a Hox morphogenetic gene network.

Publications

Forces shaping a Hox morphogenetic gene network.

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