Brian M. Parks

Individual diet has sex-dependent effects on vertebrate gut microbiota

Vertebrates harbour diverse communities of symbiotic gut microbes. Host diet is known to alter microbiota composition, implying that dietary treatments might alleviate diseases arising from altered microbial composition (‘dysbiosis’). However, it remains unclear whether diet effects are general or depend on host genotype. Here we show that gut microbiota composition depends on interactions between host diet and sex within populations of wild and laboratory fish, laboratory mice and humans. Within each of two natural fish populations (threespine stickleback and Eurasian perch), among-individual diet variation is correlated with individual differences in gut microbiota. However, these diet–microbiota associations are sex dependent. We document similar sex-specific diet–microbiota correlations in humans. Experimental diet manipulations in laboratory stickleback and mice confirmed that diet affects microbiota differently in males versus females. The prevalence of such genotype by environment (sex by diet) interactions implies that therapies to treat dysbiosis might have sex-specific effects.

Arabidopsis Seedling Growth Response and Recovery to Ethylene. A Kinetic Analysis

Responses to the plant hormone ethylene are mediated by a family of five receptors in Arabidopsis that act in the absence of ethylene as negative regulators of response pathways. In this study, we examined the rapid kinetics of growth inhibition by ethylene and growth recovery after ethylene withdrawal in hypocotyls of etiolated seedlings of wild-type and ethylene receptor-deficient Arabidopsis lines. This analysis revealed that there are two phases to growth inhibition by ethylene in wild type: a rapid phase followed by a prolonged, slower phase. Full recovery of growth occurs approximately 90 min after ethylene removal. None of the receptor null mutations tested had a measurable effect on the two phases of growth inhibition. However, loss-of-function mutations in ETR1, ETR2, and EIN4 significantly prolonged the time for recovery of growth rate after ethylene was removed. Plants with an etr1-6;etr2-3;ein4-4 triple loss-of-function mutation took longer to recover than any of the single mutants, while the ers1;ers2 double mutant had no effect on recovery rate, suggesting that receiver domains play a role in recovery. Transformation of the ers1-2;etr1-7 double mutant with wild-type genomic ETR1 rescued the slow recovery phenotype, while a His kinase-inactivated ETR1 construct did not. To account for the rapid recovery from growth inhibition, a model in which clustered receptors act cooperatively is proposed.

Molecular analysis of the phytochrome deficiency in an aurea mutant of tomato.

SummaryThe auw mutant allele of the aurea locus in tomato has previously been shown to cause deficiency for the phytochrome polypeptide (Parks et al. 1987). We have begun to characterize the molecular basis and consequences of this deficiency. Genomic Southern blot analysis indicates that there are at least two and probably more phytochrome polypeptide structural genes in tomato. RNA blot analysis shows that the auw mutant contains normal levels of phytochrome mRNA and in vitro translation of auw poly(A)+ RNA yields a phytochrome apoprotein that is quantitatively and qualitatively indistinguishable on SDS-polyacrylamide gels from that synthesized from wild-type RNA. These results indicate that the phytochrome deficiency in aurea is not the result of lack of expression of phytochrome genes but is more likely due to instability of the phytochrome polypeptide in planta. Possible reasons for such instability are discussed. Analysis of the molecular phenotype of aurea indicates that the phytochrome-mediated increase in the abundance of the mRNA encoding chlorophyll a/b binding protein (cab) is severely restricted in the mutant as compared with wild-type tomato. Thus, the auw strain exhibits defective photoregulation of gene expression consistent with its very reduced level of the phytochrome photoreceptor.

Photocontrol of stem growth.

Rapid and measurable growth rate changes that occur in seedling stems upon illumination serve as an excellent means to analyze signal transduction. Growth kinetic studies have shown how red, far-red and blue light signals are transduced via the solitary and/or coordinated action of known plant photoreceptors. These reports are consistent with current findings describing light-induced photoreceptor interaction and compartmentation.

Missense mutations define a restricted segment in the C-terminal domain of phytochrome A critical to its regulatory activity.

The phytochrome family of photoreceptors has dual molecular functions: photosensory, involving light signal perception, and regulatory, involving signal transfer to downstream transduction components. To define residues necessary specifically for the regulatory activity of phytochrome A (phyA), we undertook a genetic screen to identify Arabidopsis mutants producing wild-type levels of biologically defective but photochemically active and dimeric phyA molecules. Of eight such mutants identified, six contain missense mutations (including three in the same residue, glycine 727) clustered within a restricted segment in the C-terminal domain of the polypeptide. Quantitative photobiological analysis revealed retention of varying degrees of partial activity among the different alleles--a result consistent with the extent of conservation at the position mutated. Together with additional data, these results indicate that the photoreceptor subdomain identified here is critical to the regulatory activity of both phyA and phyB.

Phy-Gene Structure, Evolution, and Expression

The fundamental notion that phytochrome controls plant development through differential regulation of gene expression (Mohr, 1966) is now well supported by direct experimental evidence (Benfey and Chua, 1989; Gilmartin et al., 1990; Kuhlemeier et al., 1987; Nagy et al., 1988; Tobin and Silverthorne, 1985). However, the molecular mechanism by which the photoreceptor transduces its regulatory signal to genes under its control remains unknown. For some time we have approached this question by simultaneously studying the properties of the photoreceptor molecule and the negative autoregulation of phytochrome (phy) genes as a paradigm of phytochrome-regulated gene expression (Colbert, 1988; Lissemore and Quail, 1988; Quail et al., 1987b, 1990). Recent molecular-genetic studies have revealed that phytochrome is encoded by a small family of divergent and differentially regulated genes (Dehesh et al., 1990b; Sharrock and Quail, 1989); have shown that overexpression of the photoreceptor in heterologous, transgenic plants provides a system for directed mutational analysis of functional regions of the polypeptide (Boylan and Quail, 1989; Kay et al., 1989c; Keller et al., 1989); and have begun to provide insight into the cis-regulatory elements and trans-acting factors involved in phy gene transcription (Brace et al., 1989, 1990; Dehesh et al., 1990a).

The Hybrid Mouse Diversity Panel: a resource for systems genetics analyses of metabolic and cardiovascular traits.

The Hybrid Mouse Diversity Panel (HMDP) is a collection of approximately 100 well-characterized inbred strains of mice that can be used to analyze the genetic and environmental factors underlying complex traits. While not nearly as powerful for mapping genetic loci contributing to the traits as human genome-wide association studies, it has some important advantages. First, environmental factors can be controlled. Second, relevant tissues are accessible for global molecular phenotyping. Finally, because inbred strains are renewable, results from separate studies can be integrated. Thus far, the HMDP has been studied for traits relevant to obesity, diabetes, atherosclerosis, osteoporosis, heart failure, immune regulation, fatty liver disease, and host-gut microbiota interactions. High-throughput technologies have been used to examine the genomes, epigenomes, transcriptomes, proteomes, metabolomes, and microbiomes of the mice under various environmental conditions. All of the published data are available and can be readily used to formulate hypotheses about genes, pathways and interactions.

The Red Side of Photomorphogenesis

The importance of light to normal plant growth and development cannot be overstated. As sessile photoautotrophs, plants depend on efficient light capture to compete and reproduce successfully within a relatively restricted geographical realm. For this purpose, these organisms have evolved very

The phy Gene Family: Function and Expression

Plants constantly monitor and adapt to the light environment in which they find themselves (Kendrick and Kronenberg, 1986). To accomplish this task they employ a set of regulatory photoreceptors of which phytochrome is the best characterized (Quail, 1991, 1993). Although phytochrome had long been thought of by many as a single homogeneous entity, the complexities of environmental light signals and the diversity of plants’ responses to them had over the years increasingly suggested to photophysiologists the possible involvement of more than one phytochrome in mediating these responses (Hillman, 1967; Smith and Whitelam, 1990; Smith, 1992). Indeed, parallel biochemical, immunochemical and spectroscopic studies provided steadily accumulating evidence for the existence of at least two molecular species of the photoreceptor (Furuya, 1989). Most recently, molecular evidence that phytochrome is in fact a family of photoreceptors encoded by five divergent genes, designated phyA, phyB, phyC, phyD and phyE, was obtained from studies with Arabidopsis (Sharrock and Quail, 1989; R. A. Sharrock, pers. comm.).