Predicting the Evolution of Syntenies—An Algorithmic Review

Syntenies are genomic segments of consecutive genes identified by a certain conservation in gene content and order. The notion of conservation may vary from one definition to another, the more constrained requiring identical gene contents and gene orders, while more relaxed definitions just require a certain similarity in gene content, and not necessarily in the same order. Regardless of the way they are identified, the goal is to characterize homologous genomic regions, i.e., regions deriving from a common ancestral region, reflecting a certain gene co-evolution that can enlighten important functional properties. In addition of being able to identify them, it is also necessary to infer the evolutionary history that has led from the ancestral segment to the extant ones. In this field, most algorithmic studies address the problem of inferring rearrangement scenarios explaining the disruption in gene order between segments with the same gene content, some of them extending the evolutionary model to gene insertion and deletion. However, syntenies also evolve through other events modifying their content in genes, such as duplications, losses or horizontal gene transfers, i.e., the movement of genes from one species to another. Although the reconciliation approach between a gene tree and a species tree addresses the problem of inferring such events for single-gene families, little effort has been dedicated to the generalization to segmental events and to syntenies. This paper reviews some of the main algorithmic methods for inferring ancestral syntenies and focus on those integrating both gene orders and gene trees.

Plastome structure and adaptive evolution of Calanthe s.l. species

Calanthe s.l. is the most diverse group in the tribe Collabieae (Orchidaceae), which are pantropical in distribution. Illumina sequencing followed by de novo assembly was used in this study, and the plastid genetic information of Calanthe s.l. was used to investigate the adaptive evolution of this taxon. Herein, the complete plastome of five Calanthe s.l. species (Calanthe davidii, Styloglossum lyroglossa, Preptanthe rubens, Cephalantheropsis obcordata, and Phaius tankervilliae) were determined, and the two other published plastome sequences of Calanthe s.l. were added for comparative analyses to examine the evolutionary pattern of the plastome in the alliance. The seven plastomes ranged from 150,181 bp (C. delavayi) to 159,014 bp (C. davidii) in length and were all mapped as circular structures. Except for the three ndh genes (ndhC, ndhF, and ndhK) lost in C. delavayi, the remaining six species contain identical gene orders and numbers (115 gene). Nucleotide diversity was detected across the plastomes, and we screened 14 mutational hotspot regions, including 12 non-coding regions and two gene regions. For the adaptive evolution investigation, three species showed positive selected genes compared with others, C. obcordata (cemA), S. lyroglossa (infA, ycf1 and ycf2) and C. delavayi (nad6 and ndhB). Six genes were under site-specific positive selection in Calanthe s.l., namely, accD, ndhB, ndhD, rpoC2, ycf1, and ycf2, most of which are involved in photosynthesis. These results, including the new plastomes, provide resources for the comparative plastome, breeding, and plastid genetic engineering of orchids and flowering plants.

Toward a resolution of the cosmopolitan Botryllus schlosseri species complex (Ascidiacea, Styelidae): mitogenomics and morphology of clade E (Botryllus gaiae)

Botryllus schlosseri is a model colonial ascidian and a marine invader. It is currently recognized as a species complex comprising five genetically divergent clades, with clade A globally distributed and clade E found only in Europe. This taxon has also been recently redescribed by designation of a clade A specimen as the neotype. To clarify the taxonomic status of clade E and its relationship to clade A, we examine the entire mitochondrial genome and study the morphology of clade E. The mitogenome of clade E has an identical gene order to clade A, but substantially differs in the size of several non-coding regions. Remarkably, the nucleotide divergence of clade A-clade E is incompatible with the intraspecies ascidian divergence, but similar to the congeneric one and almost identical to the divergence between species once considered morphologically indistinguishable (e.g. the pair Ciona intestinalis (Linnaeus, 1767)-Ciona robusta Hoshino & Tokioka, 1967, and the pair Botrylloides niger Herdman, 1886-Botrylloides leachii (Savigny, 1816)). Clade E differs morphologically from the Botryllusschlosseri neotype mainly in the number and appearance of the stomach folds, and the shape of the anal opening, the first intestinal loop and the typhlosole. Our integrative taxonomical approach clearly distinguishes clade E as a species separate from Botryllusschlosseri, with unique morphological and molecular characters. Therefore, we here describe clade E as the new species Botryllus gaiae sp. nov.

Germline DNA repair mutations in men with prostate cancer are less frequent in African Americans as compared with Caucasians.

258 Background: Pathogenic DNA repair defects are well described in Caucasian (C) men with prostate cancer (PCa) but comparative data on African-American (AA) men are sparse. Methods: Germline testing for DNA repair defects were assayed by Invitae (Invitae.com). Pathogenic variants in 14 genes were compared between AA and C men with PCa; these particular genes were also assessed by Pritchard et al NEJM 375:443, 2016. Identical gene panels were not used in all men, thus variations in assay numbers from gene to gene are noted. Chi square was used to compare proportions. Results: In the 14 genes, there were 16/214 (7.5%) AA men and 347/2488 (13.9%) C men with pathogenic findings (p=0.008). As shown in the Table, the most common pathogenic variants in AA men were BRCA2 (6/214, 2.8%), BRCA1 (3/213, 1.4%), PALB2 (2/182, 1.1%), ATM (2/206, 1.0%), RAD51C (1/148, 0.68%), CHEK2 (1/207, 0.48%), and PMS2 (1/212, 0.47%). In contrast to C men in this series, no AA men had pathogenic mutations in BARD1, BRIP1, MLH1, MSH2, MSH6, NBN, or RAD51D. Pathogenic CHEK2 was less commonly detected in AA as compared to C (p=0.03) in this dataset. Comparing our C men revealed no differences in the proportion of men with pathogenic findings compared to Pritchard et al (13.9% here vs 11.8%, P=0.15). Conclusions: AA men with PCa are less likely to have pathogenic DNA repair mutations among these 14 assayed DNA repair genes compared to C men. Limitations regarding lack of stage, Gleason scores, and FH are notable. Details on gene assays and comparison to Pritchard et al NEJM 375:443, 2016 [Table: see text]

Aspergillus fumigatusPhotobiology Illuminates the Marked Heterogeneity between Isolates

ABSTRACTThe given strain ofAspergillus fumigatusunder study varies across laboratories, ranging from a few widely used “standards,” e.g., Af293 or CEA10, to locally acquired isolates that may be unique to one investigator. Since experiments concerning physiology or gene function are seldom replicated by others, i.e., in a differentA. fumigatusbackground, the extent to which behavioral heterogeneity exists within the species is poorly understood. As a proxy for assessing such intraspecies variability, we analyzed the light response of 15A. fumigatusisolates and observed striking quantitative and qualitative heterogeneity among them. The majority of the isolates fell into one of two seemingly mutually exclusive groups: (i) “photopigmenters” that robustly accumulate hyphal melanin in the light and (ii) “photoconidiators” that induce sporulation in the light. These two distinct responses were both governed by the same upstream blue light receptor, LreA, indicating that a specific protein’s contribution can vary in a strain-dependent manner. Indeed, while LreA played no apparent role in regulating cell wall homeostasis in strain Af293, it was essential in that regard in strain CEA10. The manifest heterogeneity in the photoresponses led us to compare the virulence levels of selected isolates in a murine model; remarkably, the virulence did vary greatly, although not in a manner that correlated with their overt light response. Taken together, these data highlight the extent to which isolates ofA. fumigatuscan vary, with respect to both broad physiological characteristics (e.g., virulence and photoresponse) and specific protein functionality (e.g., LreA-dependent phenotypes).IMPORTANCEThe current picture ofAspergillus fumigatusbiology is akin to a collage, patched together from data obtained from disparate “wild-type” strains. In a systematic assessment of 15A. fumigatusisolates, we show that the species is highly heterogeneous with respect to its light response and virulence. Whereas some isolates accumulate pigments in light as previously reported with strain Af293, most induce sporulation which had not been previously observed. Other photoresponsive behaviors are also nonuniform, and phenotypes of identical gene deletants vary in a background-dependent manner. Moreover, the virulence of several selected isolates is highly variable in a mouse model and apparently does not track with any observed light response. Cumulatively, this work illuminates the fact that data obtained with a singleA. fumigatusisolate are not necessarily predictive of the species as whole. Accordingly, researchers should be vigilant when making conclusions about their own work or when interpreting data from the literature.

Cognitive Domains Function Complementation by NTNG Gene Paralogs

ABSTRACTGene duplication was proposed by S.Ohno (1) as a key mechanism of a novel gene function evolution. A pair of gene paralogs, NTNG1 and NTNG2, sharing identical gene and protein structures and encoding similar proteins, forms a functional complement subfunctionalising (SF) within cognitive domains and forming cognitive endophenotypes, as detected by Intellectual Quotient (IQ) tests (2). Both NTNG paralogs are associated with autism spectrum disorder (ASD), bipolar disorder (BD) and schizophrenia (SCZ), with unique nonoverlapping segregation among the other 15 cognitive disorders (CD), emphasizing an evolutionary gain-dependent link between advanced cognitive functions and concomitant neurocognitive pathologies. Complementary expression and human brain transcriptome composition of the paralogs explains the observed phenomena of their functional complementarity. The lowest identity among NTNGs is found in a middle of encoded by them proteins designated as uknown (Ukd) domain. NTNG1 contains anthropoid-specific constrained regions, and both genes contain non-coding conserved sequences underwent accelerated evolution in human. NTNG paralogs SF perturbates “structure drives function” concept at protein and gene levels. The paralogs function diversification forms a so-called “Cognitive Complement (CC)”, a product of gene duplication and subsequent cognitive subfunction bifurcation among the NTNG gene duplicates.

Transgenerational Transmission of Stress Pathology

The impact of the environment early in life on long-term outcomes is well known. Stressful experiences during pre- and postnatal development can modulate the genetic programming of specific brain circuits underlying emotional and cognitive aspects of behavioral adaptation to stressful experiences later in life. Furthermore, there is documented evidence for gene-environment interactions in the context of early-life stress. Identical gene variants can be associated with different phenotypes depending on environmental factors. DNA methylation, an enzymatically-catalyzed modification of the DNA, is the mechanism through which phenotypes are regulated. The dynamics and plasticity of epigenetic mechanisms can have short-term, long-term, or transgenerational consequences. In epigenetic research, rodent models have targeted several behavioral and emotional phenotypes. These models have contributed significantly to our understanding of the environmental regulation of the developmental brain in early life. This review will highlight studies with rats and mice on epigenetic processes in fetal programming of stress-related mental disorders.