Extensive intron gain in the ancestor of placental mammals

Background

Genetic plasticity may be understood as the ability of a functional gene network to tolerate alterations in its components or structure. Usually, the studies involving gene modifications in the course of the evolution are concerned to nucleotide sequence alterations in closely related species. However, the analysis of large scale data about the distribution of gene families in non-exclusively closely related species can provide insights on how plastic or how conserved a given gene family is. Here, we analyze the abundance and diversity of all Eukaryotic Clusters of Orthologous Groups (KOG) present in STRING database, resulting in a total of 4,850 KOGs. This dataset comprises 481,421 proteins distributed among 55 eukaryotes.

Results

We propose an index to evaluate the evolutionary plasticity and conservation of an orthologous group based on its abundance and diversity across eukaryotes. To further KOG plasticity analysis, we estimate the evolutionary distance average among all proteins which take part in the same orthologous group. As a result, we found a strong correlation between the evolutionary distance average and the proposed evolutionary plasticity index. Additionally, we found low evolutionary plasticity in Saccharomyces cerevisiae genes associated with inviability and Mus musculus genes associated with early lethality. At last, we plot the evolutionary plasticity value in different gene networks from yeast and humans. As a result, it was possible to discriminate among higher and lower plastic areas of the gene networks analyzed.

Conclusions

The distribution of gene families brings valuable information on evolutionary plasticity which might be related with genetic plasticity. Accordingly, it is possible to discriminate among conserved and plastic orthologous groups by evaluating their abundance and diversity across eukaryotes.

Reviewers

This article was reviewed by Prof Manyuan Long, Hiroyuki Toh, and Sebastien Halary.     

A map of human protein interactions derived from co‐expression of human mRNAs and their orthologs

The human protein interaction network will offer global insights into the molecular organization of cells and provide a framework for modeling human disease, but the network's large scale demands new approaches. We report a set of 7000 physical associations among human proteins inferred from indirect evidence: the comparison of human mRNA co‐expression patterns with those of orthologous genes in five other eukaryotes, which we demonstrate identifies proteins in the same physical complexes. To evaluate the accuracy of the predicted physical associations, we apply quantitative mass spectrometry shotgun proteomics to measure elution profiles of 3013 human proteins during native biochemical fractionation, demonstrating systematically that putative interaction partners tend to co‐sediment. We further validate uncharacterized proteins implicated by the associations in ribosome biogenesis, including WBSCR20C, associated with Williams–Beuren syndrome. This meta‐analysis therefore exploits non‐protein‐based data, but successfully predicts associations, including 5589 novel human physical protein associations, with measured accuracies of 54±10%, comparable to direct large‐scale interaction assays. The new associations’ derivation from conserved in vivo phenomena argues strongly for their biological relevance.     

Population fluctuations affect inference in ecological networks of multi‐species interactions

Local abundance and population fluctuations are key factors affecting the realized interaction frequencies in biotic interactions, but they are commonly ignored when network metrics are calculated over aggregated sets of observations. Here we studied how abundance fluctuations (i.e. demographic and stochastic population dynamics in one of the trophic levels) may affect derived network‐level inferences in bipartite ecological networks. Variation at both the species and network level in network indices (d’, Dependence, Fisher's alpha diversity for both levels, H₂’, weighted NODF) were strongly correlated with the extent of abundance fluctuations, with a strong effect of environmental stochasticity on all indices except NODF; this was the only index for which considerable variation was caused by varying carrying capacities among species. Binary connectance, in turn, does not take interaction frequency (and thus abundance) into account and was only influenced by abundance fluctuations at low population sizes if this led to non‐occurrence of ‘true’ interactions. Overall, abundance and population dynamics are likely to play an important role in determining what is commonly observed and summarized into ecological networks. We suggest that ecological network inference should account for underlying population dynamics and uncertainty in what is observed as interaction frequencies, modelling mechanisms at operative organisational levels below the network rather than using aggregated data of observations. Modelling population dynamics may be a valuable tool in this field to conceptualize and tease apart different sources of variation and express uncertainty in our inference from small samples.     

Phosphoproteomic analysis of wild‐type and antimony‐resistant Leishmania braziliensis lines by 2D‐DIGE technology

Protein phosphorylation is one of the most studied post‐translational modifications that is involved in different cellular events in Leishmania. In this study, we performed a comparative phosphoproteomics analysis of potassium antimonyl tartrate (SbIII)‐resistant and ‐susceptible lines of Leishmania braziliensis using a 2D‐DIGE approach followed by MS. In order to investigate the differential phosphoprotein abundance associated with the drug‐induced stress response and SbIII‐resistance mechanisms, we compared nontreated and SbIII‐treated samples of each line. Pair wise comparisons revealed a total of 116 spots that showed a statistically significant difference in phosphoprotein abundance, including 11 and 34 spots specifically correlated with drug treatment and resistance, respectively. We identified 48 different proteins distributed into seven biological process categories. The category “protein folding/chaperones and stress response” is mainly implicated in response to SbIII treatment, while the categories “antioxidant/detoxification,” “metabolic process,” “RNA/DNA processing,” and “protein biosynthesis” are modulated in the case of antimony resistance. Multiple sequence alignments were performed to validate the conservation of phosphorylated residues in nine proteins identified here. Western blot assays were carried out to validate the quantitative phosphoproteome analysis. The results revealed differential expression level of three phosphoproteins in the lines analyzed. This novel study allowed us to profile the L. braziliensis phosphoproteome, identifying several potential candidates for biochemical or signaling networks associated with antimony resistance phenotype in this parasite.     

Novel proteins for homocysteine biosynthesis in anaerobic microorganisms

The metabolic network for sulfide assimilation and trafficking in methanogens is largely unknown. To discover novel proteins required for these processes, we used bioinformatics to identify genes co‐occurring with the protein biosynthesis enzyme SepCysS, which converts phosphoseryl‐tRNA^Cys to cysteinyl‐tRNA^Cys in nearly all methanogens. Exhaustive analysis revealed three conserved protein families, each containing molecular signatures predicting function in sulfur metabolism. One of these families, classified within clusters of orthologous groups (COG) 1900, possesses two conserved cysteine residues and is often found in genomic contexts together with known sulfur metabolic genes. A second protein family is predicted to bind two 4Fe‐4S clusters. All three genes were also identified in more than 50 strictly anaerobic bacterial genera from nine distinct phyla. Gene‐deletion and growth experiments in Methanosarcina acetivorans, using sulfide as the sole sulfur source, demonstrate that two of the proteins (MA1821 and MA1822) are essential to homocysteine biosynthesis in a background lacking an additional gene for sulfur insertion into homocysteine. Mutational analysis confirms the importance of several structural elements, including a conserved cysteine residue and the predicted 4Fe‐4S cluster‐binding domain.     

Phylogenetic conservatism in plant‐soil feedback and its implications for plant abundance

We examined whether plant‐soil feedback and plant‐field abundance were phylogenetically conserved. For 57 co‐occurring native and exotic plant species from an old field in Canada, we collected a data set on the effects of three soil biota treatments on plant growth: net whole‐soil feedback (combined effects of mutualists and antagonists), feedback with arbuscular mycorrhizal fungi (AMF) collected from soils of conspecific plants, and feedback with Glomus etunicatum, a dominant mycorrhizal fungus. We found phylogenetic signal in both net whole‐soil feedback and feedback with AMF of conspecifics; conservatism was especially strong among native plants but absent among exotics. The abundance of plants in the field was also conserved, a pattern underlain by shared plant responses to soil biota. We conclude that soil biota influence the abundance of close plant relatives in nature.     

Quantitative trait loci mapping and gene network analysis implicate protocadherin‐15 as a determinant of brain serotonin transporter expression

Presynaptic serotonin (5‐hydroxytryptamine, 5‐HT) transporters (SERT) regulate 5‐HT signaling via antidepressant‐sensitive clearance of released neurotransmitter. Polymorphisms in the human SERT gene (SLC6A4) have been linked to risk for multiple neuropsychiatric disorders, including depression, obsessive‐compulsive disorder and autism. Using BXD recombinant inbred mice, a genetic reference population that can support the discovery of novel determinants of complex traits, merging collective trait assessments with bioinformatics approaches, we examine phenotypic and molecular networks associated with SERT gene and protein expression. Correlational analyses revealed a network of genes that significantly associated with SERT mRNA levels. We quantified SERT protein expression levels and identified region‐ and gender‐specific quantitative trait loci (QTLs), one of which associated with male midbrain SERT protein expression, centered on the protocadherin‐15 gene (Pcdh15), overlapped with a QTL for midbrain 5‐HT levels. Pcdh15 was also the only QTL‐associated gene whose midbrain mRNA expression significantly associated with both SERT protein and 5‐HT traits, suggesting an unrecognized role of the cell adhesion protein in the development or function of 5‐HT neurons. To test this hypothesis, we assessed SERT protein and 5‐HT traits in the Pcdh15 functional null line (Pcdh15^av‐3J), studies that revealed a strong, negative influence of Pcdh15 on these phenotypes. Together, our findings illustrate the power of multidimensional profiling of recombinant inbred lines in the analysis of molecular networks that support synaptic signaling, and that, as in the case of Pcdh15, can reveal novel relationships that may underlie risk for mental illness .     

Pollinator specialization increases with a decrease in a mass‐flowering plant in networks inferred from DNA metabarcoding

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Quantitative analysis of protein interaction network dynamics in yeast

Many cellular functions are mediated by protein–protein interaction networks, which are environment dependent. However, systematic measurement of interactions in diverse environments is required to better understand the relative importance of different mechanisms underlying network dynamics. To investigate environment‐dependent protein complex dynamics, we used a DNA‐barcode‐based multiplexed protein interaction assay in Saccharomyces cerevisiae to measure in vivo abundance of 1,379 binary protein complexes under 14 environments. Many binary complexes (55%) were environment dependent, especially those involving transmembrane transporters. We observed many concerted changes around highly connected proteins, and overall network dynamics suggested that “concerted” protein‐centered changes are prevalent. Under a diauxic shift in carbon source from glucose to ethanol, a mass‐action‐based model using relative mRNA levels explained an estimated 47% of the observed variance in binary complex abundance and predicted the direction of concerted binary complex changes with 88% accuracy. Thus, we provide a resource of yeast protein interaction measurements across diverse environments and illustrate the value of this resource in revealing mechanisms of network dynamics.     

Dynamic evolution of bz orthologous regions in the Andropogoneae and other grasses

Genome structure exhibits remarkable plasticity within Zea mays. To examine how haplotype structure has evolved within the Andropogoneae tribe, we have analyzed the bz gene‐rich region of maize (Zea mays), the Zea teosintes mays ssp. mexicana, luxurians and diploperennis, Tripsacum dactyloides, Coix lacryma‐jobi and Sorghum propinquum. We sequenced and annotated BAC clones from these species and re‐annotated the orthologous Sorghum bicolor region. Gene colinearity in the region is well conserved within the genus Zea. However, the orthologous regions of Coix and Sorghum exhibited several micro‐rearrangements relative to Zea, including addition, truncation and deletion of genes. The stc1 gene, involved in the production of a terpenoid insect defense signal, is evolving particularly fast, and its progressive disappearance from some species is occurring by microhomology‐mediated recombination. LTR retrotransposons are the main contributors to the dynamic evolution of the bz region. Common transposon insertion sites occur among haplotypes from different Zea mays sub‐species, but not outside the species. As in Zea, different patterns of interspersion between genes and retrotransposons are observed in Sorghum. We estimate that the mean divergence times between maize and Tripsacum, Coix and Sorghum are 8.5, 12.1 and 12.4 million years ago, respectively, and that between Coix and Sorghum is 9.3 million years ago. A comparison of the bz orthologous regions of Zea, Sorghum and Coix with those of Brachypodium, Setaria and Oryza allows us to infer how the region has evolved by addition and deletion of genes in the approximately 50 million years since these genera diverged from a common progenitor.     

Comparative Genomics Reveals Long, Evolutionarily Conserved, Low-Complexity Islands in Yeast Proteins

Eukaryotic proteomes abound in low-complexity sequences, including tandem repeats and regions with significantly biased amino acid compositions. We assessed the functional importance of compositionally biased sequences in the yeast proteome using an evolutionary analysis of 2838 orthologous open reading frame (ORF) families from three Saccharomyces species (S. cerevisiae, S. bayanus, and S. paradoxus). Sequence conservation was measured by the amino acid sequence variability and by the ratio of nonsynonymous-to-synonymous nucleotide substitutions (K _a /K _s ) between pairs of orthologous ORFs. A total of 1033 ORF families contained one or more long (at least 45 residues), low-complexity islands as defined by a measure based on the Shannon information index. Low-complexity islands were generally less conserved than ORFs as a whole; on average they were 50% more variable in amino acid sequences and 50% higher in K _a /K _s ratios. Fast-evolving low-complexity sequences outnumbered conserved low-complexity sequences by a ratio of 10 to 1. Sequence differences between orthologous ORFs fit well to a selectively neutral Poisson model of sequence divergence. We therefore used the Poisson model to identify conserved low-complexity sequences. ORFs containing the 33 most conserved low-complexity sequences were overrepresented by those encoding nucleic acid binding proteins, cytoskeleton components, and intracellular transporters. While a few conserved low-complexity islands were known functional domains (e.g., DNA/RNA-binding domains), most were uncharacterized. We discuss how comparative genomics of closely related species can be employed further to distinguish functionally important, shorter, low-complexity sequences from the vast majority of such sequences likely maintained by neutral processes. [Reviewing Editor: Dr. Stuart Newfeld]     

Low levels of ribosomal RNA partly account for the very high photosynthetic phosphorus‐use efficiency of Proteaceae species

Proteaceae species in south‐western Australia occur on phosphorus‐ (P) impoverished soils. Their leaves contain very low P levels, but have relatively high rates of photosynthesis. We measured ribosomal RNA (rRNA) abundance, soluble protein, activities of several enzymes and glucose 6‐phosphate (Glc6P) levels in expanding and mature leaves of six Proteaceae species in their natural habitat. The results were compared with those for Arabidopsis thaliana. Compared with A. thaliana, immature leaves of Proteaceae species contained very low levels of rRNA, especially plastidic rRNA. Proteaceae species showed slow development of the photosynthetic apparatus (‘delayed greening’), with young leaves having very low levels of chlorophyll and Calvin–Benson cycle enzymes. In mature leaves, soluble protein and Calvin–Benson cycle enzyme activities were low, but Glc6P levels were similar to those in A. thaliana. We propose that low ribosome abundance contributes to the high P efficiency of these Proteaceae species in three ways: (1) less P is invested in ribosomes; (2) the rate of growth and, hence, demand for P is low; and (3) the especially low plastidic ribosome abundance in young leaves delays formation of the photosynthetic machinery, spreading investment of P in rRNA. Although Calvin–Benson cycle enzyme activities are low, Glc6P levels are maintained, allowing their effective use.