Experimental Evaluation of a Direct Fitness Effect of the De Novo Evolved Mouse Gene Pldi.

De novo evolved genes emerge from random parts of noncoding sequences and have, therefore, no homologs from which a function could be inferred. While expression analysis and knockout experiments can provide insights into the function, they do not directly test whether the gene is beneficial for its carrier. Here, we have used a seminatural environment experiment to test the fitness of the previously identified de novo evolved mouse gene Pldi, which has been implicated to have a role in sperm differentiation. We used a knockout mouse strain for this gene and competed it against its parental wildtype strain for several generations of free reproduction. We found that the knockout (ko) allele frequency decreased consistently across three replicates of the experiment. Using an approximate Bayesian computation framework that simulated the data under a demographic scenario mimicking the experiment's demography, we could estimate a selection coefficient ranging between 0.21 and 0.61 for the wildtype allele compared to the ko allele in males, under various models. This implies a relatively strong selective advantage, which would fix the new gene in less than hundred generations after its emergence.

Connective tissue matrices from placental disc for wound healing: mini-review.

Wound management is a complex procedure that includes multiple factors that play major roles in the healing process. Extracellular matrix-based approaches are emerging strategies for promoting wound healing. The extracellular matrix is an extensive three-dimensional molecular network comprising a variety of fibrous proteins, glycosaminoglycans, and proteoglycans. One of the rich sources of extracellular matrix components is placental tissues, which have a long history of use in tissue repair and regeneration. PURPOSE OF WORK: This mini-review focuses on essential characteristics of placental disc, comparison of four commercially available placental connective matrices (Axiofill, Dermavest, Plurivest, and Interfyl) obtained from the placental disc, and their supporting studies in the use of wound healing applications.

Intron exon boundary junctions in human genome have in-built unique structural and energetic signals.

Precise identification of correct exon-intron boundaries is a prerequisite to analyze the location and structure of genes. The existing framework for genomic signals, delineating exon and introns in a genomic segment, seems insufficient, predominantly due to poor sequence consensus as well as limitations of training on available experimental data sets. We present here a novel concept for characterizing exon-intron boundaries in genomic segments on the basis of structural and energetic properties. We analyzed boundary junctions on both sides of all the exons (3 28 368) of protein coding genes from human genome (GENCODE database) using 28 structural and three energy parameters. Study of sequence conservation at these sites shows very poor consensus. It is observed that DNA adopts a unique structural and energy state at the boundary junctions. Also, signals are somewhat different for housekeeping and tissue specific genes. Clustering of 31 parameters into four derived vectors gives some additional insights into the physical mechanisms involved in this biological process. Sites of structural and energy signals correlate well to the positions playing important roles in pre-mRNA splicing.

What DNA methylation modifications and/or genetic variations interact with childhood maltreatment in the development of depression: A systematic review.

BACKGROUND: Child maltreatment predicts a significant risk factor for depression. The relationship between child maltreatment and depression has been shown to vary as a function of genetic factors. There have been very few systematic reviews conducted to date to synthesize what DNA methylations and/ or genetic variations interact with childhood maltreatment in the course of depression. This systematic review aimed to provide an overview of DNA methylation modifications with/without genetic variations associated with childhood maltreatment in depression. METHODS: Computerized and manual search on six databases (EMBASE, HealthStar, PsychoInfo, Medline, PubMed and Cochrane Library) and grey literature up to June 30th 2018 were conducted. Studies were critically evaluated for their eligibility and study quality. RESULTS: The initial search resulted in 196 articles. Five articles met the eligibility criteria being included in this review. All the selected studies were from the United States and published within the last five years. Changes in ID3, TPPP, GRIN1, and OXTR DNA methylation sites were found to be involved in the childhood maltreatment-depression relationship. LIMITATIONS: The number of eligible articles included in this review was small. Selected articles had small sample sizes. A high degree of heterogeneity was found. It is difficult to conclude what the roles of DNA methylation modifications are in the relationship between maltreatment and depression. Population stratification has not been extensively studied so far and should be considered in the further research. CONCLUSIONS: This review synthesizes an overview of the interaction between childhood maltreatment, DNA methylation modifications and genetic variations in depression. Findings of this review highlight an urgent need for genetic and epigenetic research in the area of childhood maltreatment and depression. Future etiological explorations should target on the above identified sites.

Toward a Universal Structural and Energetic Model for Prokaryotic Promoters.

With almost no consensus promoter sequence in prokaryotes, recruitment of RNA polymerase (RNAP) to precise transcriptional start sites (TSSs) has remained an unsolved puzzle. Uncovering the underlying mechanism is critical for understanding the principle of gene regulation. We attempted to search the hidden code in ∼16,500 promoters of 12 prokaryotes representing two kingdoms in their structure and energetics. Twenty-eight fundamental parameters of DNA structure including backbone angles, basepair axis, and interbasepair and intrabasepair parameters were used, and information was extracted from x-ray crystallography data. Three parameters (solvation energy, hydrogen-bond energy, and stacking energy) were selected for creating energetics profiles using in-house programs. DNA of promoter regions was found to be inherently designed to undergo a change in every parameter undertaken for the study, in all prokaryotes. The change starts from some distance upstream of TSSs and continues past some distance from TSS, hence giving a signature state to promoter regions. These signature states might be the universal hidden codes recognized by RNAP. This observation was reiterated when randomly selected promoter sequences (with little sequence conservation) were subjected to structure generation; all developed into very similar three-dimensional structures quite distinct from those of conventional B-DNA and coding sequences. Fine structural details at important motifs (viz. -11, -35, and -75 positions relative to TSS) of promoters reveal novel to our knowledge and pointed insights for RNAP interaction at these locations; it could be correlated with how some particular structural changes at the -11 region may allow insertion of RNAP amino acids in interbasepair space as well as facilitate the flipping out of bases from the DNA duplex.