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The value of structural variants to conservation genomics in the pangenome era.

Structural variants (SVs) comprise an axis of genetic diversity with strong consequences for phenotype and fitness, making them a potentially important target for conservation genomics. Here, we review how and why SVs can play a role in conservation genomics; the different types of SVs and how they can affect phenotype; and how pangenomes and long-read sequencing are illuminating their evolution in populations, including small populations and those of conservation concern. SVs comprise multinucleotide mutations including insertions, deletions, transpositions, inversions, and other multinucleotide mutations, often overlapping genes and other functional genome regions. As a result, SVs often play important roles in phenotypic evolution and local adaptation and can contribute substantially to genetic load in inbred populations. However, our understanding of the factors influencing SV diversity in populations is still in its infancy and is complicated by the vast range of sizes, effects, and mechanisms of formation of these mutations. We argue that SVs are an important axis of genetic diversity which should be characterized alongside more traditional metrics of genetic diversity in conservation contexts. There are a number of analytical challenges to detecting and studying SVs, but analyses aimed at understanding the role of SVs in inbreeding load and population health are rapidly becoming realizable goals, accelerated by new technologies and analytical approaches. New tools, including population-scale long-read sequencing and pangenome approaches, are beginning to make SVs accessible in ways which can be readily applied in conservation settings.

Genomic Structural Variation↗

Evolution and Expression Divergence of Legume PAL Genes Suggest Associations with Drought Response and Root Nodule Development.

Comparative genomic analyses provide insight into the mechanisms underlying gene-family evolution and crop adaptation. Here, we used the legume phenylalanine ammonia-lyase (PAL) gene family as a model and integrated pan-genomic, phylogenetic, molecular evolutionary, duplication-mode, and transcriptomic analyses, while developing GFtool for gene family identification. Across 45 genomes, we identified 302 PAL genes and classified them into five Groups. Groups 1-3 represented ancient lineages shared with outgroups, whereas Groups 4 and 5 were legume-specific. Molecular-clock analyses placed the divergence of Group 2 near the Paleocene-Eocene transition, while Groups 4 and 5 diversified from the middle Eocene to the early Oligocene. WGD/segmental duplication broadly contributed to PAL copy-number expansion, whereas tandem duplication was enriched in Group 5 of Papilionoideae. Group 2 genes showed drought-induced expression, whereas Group 5 genes were associated with early root nodule development. GFtool provides a scalable framework for gene-family studies.

Fabaceae↗

Experimental evidence that predation promotes divergence in adaptive radiation.

Adaptive radiation is the evolution of ecological and phenotypic diversity within a rapidly multiplying lineage. Recent studies have identified general patterns in adaptive radiation and inferred that resource competition is a primary factor driving phenotypic divergence. The role and importance of other processes, such as predation, remains controversial. Here we use Timema stick insects to show that adaptive radiation can be driven by divergent selection from visual predators. Ecotypes using different host-plant species satisfy criteria for the early stages of adaptive radiation and differ in quantitative aspects of color, color pattern, body size, and body shape. A manipulative field experiment demonstrates that the direction and strength of divergent selection on these traits is strongly positively correlated with the direction and magnitude of their population divergence in nature but only when selection is estimated in the presence of predation. Our results indicate that both competition and predation may commonly serve as mechanisms of adaptive radiation.

Adaptation, Biological↗

Functional conservation of the promoter regions of vertebrate tyrosinase genes.

Tyrosinase is the key enzyme for synthesizing melanin pigments, which primarily determine mammalian skin coloration. Considering the important roles of pigments in the evolution and the adaptation of vertebrates, phylogenetic changes in the coding and flanking regulatory sequences of the tyrosinase gene are particularly intriguing. We have now cloned cDNA encoding tyrosinase from Japanese quail and snapping turtle. These nonmammalian cDNA are highly homologous to those of the mouse and human tyrosinases, whereas the 5' flanking sequences are far less conserved except for a few short sequence motifs. Nevertheless, we demonstrate that the 5' flanking sequences from the quail or turtle tyrosinase genes are capable of directing the expression of a fused mouse tyrosinase cDNA when introduced into cultured mouse albino melanocytes. This experimental method, which reveals the functional conservation of regulatory sequences in one cell type (the melanocyte), may be utilized to evaluate phylogenetic differences in mechanisms controlling specific gene expression in many other types of cells. We also provide evidence that the 5' flanking sequences from these nonmammalian genes are functional in vivo by producing transgenic mice. Phylogenetic changes of vertebrate tyrosinase promoters and the possible involvement of conserved sequence motifs in melanocyte-specific expression of tyrosinase are discussed.

5' Flanking Region↗

In-host adaptation of Staphylococcus aureus during recurrent prosthetic joint infections: a retrospective longitudinal study.

UNLABELLED: The aim of this study was to characterize the in vivo evolution of Staphylococcus aureus strains involved in recurrent prosthetic joint infections (PJIs) both phenotypically and genomically. We conducted a monocentric retrospective study in a 1,437-bed French teaching hospital between 2013 and 2021. All patients presenting a recurrent S. aureus-related PJI-defined as at least two strains isolated from distinct clinical samples more than 90 days apart-of the knee, hip, or shoulder were included. Clinical data were reviewed, and all isolates underwent phenotypic characterization, including antimicrobial susceptibility testing, growth rate determination, biofilm production assays, metabolic profiling (API 50 CH), and virulence evaluation using the Galleria mellonella infection model. Whole-genome sequencing (WGS) was performed for all strains, followed by analyses of core-genome multilocus sequence typing (cgMLST), resistome, virulome, and mobilome composition, and single-nucleotide polymorphisms (SNPs). Thirteen patients met inclusion criteria, yielding 55 S. aureus isolates. Eight patients experienced recurrent infections caused by genetically closely related strains throughout the clinical course (median: three strains per patient; range: 2-6), whereas five patients were infected by genetically distinct strains. At baseline, isolates were genetically diverse and susceptible to methicillin and rifampicin; two showed fluoroquinolone resistance due to grlA and/or gyrA mutations. In one patient (patient C), a recurrent isolate acquired an rpoB S486L mutation, conferring rifampicin resistance after rifampicin exposure. Due to the limited sample size, it is difficult to draw definitive conclusions from the phenotypic analyses. This study highlights the adaptive evolution of S. aureus during chronic PJIs and underscores the need for further research to better understand intra-host dynamics in long-standing infections. IMPORTANCE: This study conducted in a 1,437-bed French teaching hospital analyzed the genomic and phenotypic evolution of 55 Staphylococcus aureus strains recovered in recurrent PJIs from 13 patients. The first strains showed high genotypic diversity across 12 different sequence types. Among the 13 patients, only eight experienced a true recurrence with the same strain, while five were contaminated with a different strain of S. aureus, indicating a new infection. Moreover, this study underscores the complex within-host evolution of S. aureus and highlights the phenotypical and genotypical adaptation during chronic infection.

Staphylococcus aureus↗

Genetic mechanisms and evolutionary significance of natural variation in Arabidopsis.

Genomic studies of natural variation in model organisms provide a bridge between molecular analyses of gene function and evolutionary investigations of adaptation and natural selection. In the model plant species Arabidopsis thaliana, recent studies of natural variation have led to the identification of genes underlying ecologically important complex traits, and provided new insights about the processes of genome evolution, geographic population structure, and the selective mechanisms shaping complex trait variation in natural populations. These advances illustrate the potential for a new synthesis to elucidate mechanisms for the adaptive evolution of complex traits from nucleotide sequences to real-world environments.

Adaptation, Biological↗

Cryptic species of fig-pollinating wasps: implications for the evolution of the fig-wasp mutualism, sex allocation, and precision of adaptation.

Fig-pollinating wasps have provided model systems for developing and testing theories of the evolution of mutualism, sex allocation, and precision of adaptation. With few exceptions, previous studies have assumed one species of pollinator wasp per host fig species. Here we report genetic data demonstrating the coexistence of previously undetected cryptic fig wasp species in at least half of the host fig species surveyed. The substantial mitochondrial sequence differences (4.2-6.1%) imply old divergences ( approximately 1.5-5.1 million years ago) among these species. Furthermore, some cryptic species pairs seem to be sister taxa, whereas others clearly are not, indicating both long-term coexistence on shared hosts and the colonization of novel fig species. These findings undermine the prevalent notion of strict one-to-one specificity between cospeciating figs and their pollinators, thereby challenging existing theory concerning the evolution and stability of mutualisms. Moreover, the incorporation of the genetic information significantly improves the fit of the observed sex ratios to predictions of local mate-competition theory, further strengthening support for sex allocation theory and the precision of adaptation.

Animals↗

Acetylcholinesterase-rich pyramidal neurons in the human neocortex and hippocampus: absence at birth, development during the life span, and dissolution in Alzheimer's disease.

Acetylcholinesterase-rich pyramidal neurons in the human association neocortex and hippocampal formation are virtually absent early in life, become established by adolescence, and appear to increase in density during adulthood and perhaps even senescence. Analogous neurons are not detectable in the adult monkey brain. This novel class of neurons may represent a uniquely human adaptation in primate evolution and may provide a neuroanatomical substrate for the mental development that occurs during the adult stages of life. These phylogenetically and ontogenetically progressive neurons are also markedly vulnerable to degeneration in Alzheimer's disease.

Acetylcholinesterase↗

Distribution of MHC II (+) cells in skin of the Atlantic bottlenose dolphin (Tursiops truncatus): an initial investigation of dolphin dendritic cells.

The skin is an important tissue of the immune system; however, little is known about immune cells in dolphin skin, and very few cetacean-specific immunoreagents are available for investigative purposes. Therefore, in this study immunohistochemistry techniques were used with species-specific and non-species-specific antibodies to characterize immune cells, primarily focusing on Langerhans cells, in skin from the Atlantic bottlenose dolphin (Tursiops truncatus). An antibody to human major histocompatibility complex (MHC) class II molecules labeled cells with a dendritic-like morphology. The immunophenotype, morphology, and distribution of some of these cells are consistent with those of Langerhans cells. The cells were predominantly found in dermal papillae, primarily along the epidermal-dermal junction. Thus, the location of these cells was somewhat different from that in terrestrial mammals. Other MHC II (+) cells of varying morphology were observed deeper in the dermis, with a perivascular concentration, and had characteristics of macrophages and dermal dendritic cells. There was no immunostaining with cetacean-specific CD2 or CD21. In diseased skin, a subjective increase of MHC II (+) cells, most notably in the superficial skin layers, was associated with an ulcerative dermatitis. A few CD2 (+) cells were also present. Differences between dolphins and terrestrial mammals in terms of morphology, mechanisms of response to insult and repair, and environmental challenges may explain the modified distribution of MHC II (+) cells in dolphin skin. An elucidation of the immune cells in cetacean skin will contribute to our understanding of the evolution of functional adaptations to various environments, facilitate diagnosis of skin diseases, and define the potential for intradermal administration of vaccines and other immunotherapeutics.

Animals↗

The evolution of meiosis: recruitment and modification of somatic DNA-repair proteins.

Several DNA-damage detection and repair mechanisms have evolved to repair double-strand breaks induced by mutagens. Later in evolutionary history, DNA single- and double-strand cuts made possible immune diversity by V(D)J recombination and recombination at meiosis. Such cuts are induced endogenously and are highly regulated and controlled. In meiosis, DNA cuts are essential for the initiation of homologous recombination, and for the formation of joint molecule and crossovers. Many proteins that function during somatic DNA-damage detection and repair are also active during homologous recombination. However, their meiotic functions may be altered from their somatic roles through localization, posttranslational modifications and/or interactions with meiosis-specific proteins. Presumably, somatic repair functions and meiotic recombination diverged during evolution, resulting in adaptations specific to sexual reproduction. (c) 2005 Wiley Periodicals, Inc.

Animals↗

Neo-self antigens and the expansion of B-1 cells: lessons from atherosclerosis-prone mice.

The pathogenesis of atherosclerosis involves an inflammatory process that is modulated by the immune system, and within these complex responses we have discerned a possible role for an archetypic B-1 clone. We speculate that due to their immunogenicity and in vivo distribution the "neo"-self determinants created in oxidatively modified LDL are highly stimulatory for certain B-1 cell clones. These neo-self determinants, which can be created chemically, by somatic processes, may in fact represent the molecular analogues of somatic maturation, or even aging. These changes, including those on non-protein antigens induced by oxidative metabolism, amongst others, create neo-determinants against which the host no doubt can not develop rigorous B-cell tolerance. The onset of expression of these oxidative neo-determinants relatively late in development may well serve a useful function for the highly evolved mammalian immune system, as targeting by evolutionarily selected B-1 clones may facilitate the amplification of other useful antibody-mediated physiologic functions. As in the case of the T15 clone, these antibodies may aid in protection against common microbial pathogens. Hence we postulate that during the evolution of the adaptive immune system the neo-self antigenic milieu may have been exploited for the natural selection of primordial clonal specificities. The T15 B-1 clone may then illustrate a common paradigm in which there has been natural selection based on utility for the defense of the individual from environmental threats, as well as for possible "housekeeping" role(s) and the maintenance of cellular homeostasis.

Animals↗

Identification and sequence analysis of chicken Toll-like receptors.

Toll-like receptors (TLRs) play an important role in the recognition of microbial components. Only chicken TLR2 and -4 have been reported in the literature. The objectives of this study were to identify new chicken TLRs and to evaluate evolutionary significance of these receptors. Searching chicken genomic databases and DNA sequencing revealed five new TLRs, TLR1 (type 1 and 2), -3, -5, and -7. No chicken orthologues of mammalian TLR8, -9, or -10 were found. As in mammals, all chicken TLRs (chTLRs) share identical protein secondary structure that consists of several leucine-rich domains, a transmembrane domain, and Toll/Interleukin-1 receptor domain(s). Phylogenetic analyses indicate that the identified chTLR genes are the orthologues of TLRs in mammals. Analyses of the number of synonymous substitutions per synonymous site and nonsynonymous substitutions per nonsynonymous site indicate that the nucleotide sequences coding for the leucine-rich repeats of chicken TLR1 type 1 and type 2 were significantly under positive Darwinian selection. In contrast, the sequences of other TLRs were under purifying selection. These results support the hypothesis that one of the major evolutionary strategies of the innate immune system is to recognize a few highly conserved microbial components with several conserved TLRs. The results also indicate that the sequence changes in the ligand-binding domains of TLR1 in chickens provide adaptive advantages during evolution.

Amino Acid Sequence↗

Phylogenetic, ontogenetic and adult adaptive plasticity of rhythmic neural networks: a common neuromodulatory mechanism?

Neuromodulatory inputs are known to play a major role in the adaptive plasticity of rhythmic neural networks in adult animals. Using the crustacean stomatogastric nervous system, we have investigated the role of modulatory inputs in the development of rhythmic neural networks. We found that the same neuronal population is organised into a single network in the embryo, as opposed to the two networks present in the adult. However, these adult networks pre-exist in the embryo and can be unmasked by specific alterations of the neuromodulatory environment. Similarly, adult networks may switch back to the embryonic phenotype by manipulating neuromodulatory inputs. During development, we found that the early established neuromodulatory population display alteration in expressed neurotransmitter phenotypes, and that although the population of modulatory neurones is established early, with morphology and projection pattern similar to adult ones, their neurotransmitter phenotype may appear gradually. Therefore the abrupt switch from embryonic to adult network expression occurring at metamorphosis may be due to network reconfiguration in response to changes in modulatory input, as found in adult adaptive plasticity. Strikingly, related crustacean species express different motor outputs using the same basic network circuitry, due to species-specific alteration in neuromodulatory substances within homologous projecting neurones. Therefore we propose that alterations within neuromodulatory systems to a given rhythmic neural network displaying the same basic circuitry may account for the generation of different motor outputs throughout development (ontogenetic plasticity), adulthood (adaptive plasticity) and evolution (phylogenetic plasticity).

Animals↗

Homology model of human corticosteroid binding globulin: a study of its steroid binding ability and a plausible mechanism of steroid hormone release at the site of inflammation.

Corticosteroid binding globulin (CBG) and thyroxin binding globulin (TBG) both belong to the same SERPIN superfamily of serine-proteinase inhibitors but in the course of evolution CBG has adapted to its new role as a transport agent of insoluble hormones. CBG binds corticosteroids in plasma, delivering them to sites of inflammation to modify the inflammatory response. CBG is an effective drug carrier for genetic manipulation, and hence there is immense biological interest in the location of the hormone binding site. The crystal structure of human CBG (hCBG) has not been determined, but sequence alignment with other SERPINs suggests that it conforms as a whole to the tertiary structure shared by the superfamily. Human CBG shares 52.15% and 55.50% sequence similarity with alpha1-antitrypsin and alpha1-antichymotrypsin, respectively. Multiple sequence alignment among the three sequences shows 73 conserved regions. The molecular structures of alpha1-antitrypsin and alpha1-antichymotrypsin, the archetype of the SERPIN superfamily, obtained by X-ray diffraction methods are used to develop a homology model of hCBG. Energy minimization was applied to the model to refine the structure further. The homology model of hCBG contains 371 residues (His13 to Val383 ). The secondary structure comprises 11 helices, 15 turns and 11 sheets. The putative corticosteroid binding region is found to exist in a pocket between beta-sheets S4, S10, S11 and alpha helix H10. Both cortisol and aldosterone are docked to the elongated hydrophobic ligand binding pocket with the polar residues at the two extremities. A difference accessible surface area (DASA) study revealed that cortisol binds with the native hCBG more tightly than aldosterone. Cleavage at the Val379-Met380 peptide bond causes a deformation of hCBG (also revealed through a DASA study). This deformation could probably trigger the release of the bound hormone. Figure Stereoscopic view of the ribbon diagram of hCBG complexed with cortisol. The bound cortisol is shown in space filling model in blue. Helices and sheets are shown in red and magenta respectively. Turns are shown in yellow.

Adrenal Cortex Hormones↗

Progesterone receptors in the oviduct of a viviparous snake (Nerodia): correlations with ovarian function and plasma steroid levels.

The physiological significance of progesterone during gestation in viviparous reptiles is not understood, although there is strong evidence for luteal synthesis and secretion of this steroid. In a previous study we characterized an oviduct progesterone receptor in the viviparous snake, Nerodia, and in this study we describe changes in receptor during the reproductive cycle. Correlation of the amount of receptor with changes in plasma estradiol 17 beta and progesterone and the effect of injected hormones suggest that the receptor may be regulated by these steroids as in mammals. Thus, the basis exists for target organ responses to progesterone and provides additional evidence for the potential role of progesterone in the early hormonal adaptations in the evolution of viviparity.

Animals↗

Marker chromosome stability associated with neoplastic transformation of human uroepithelial cells.

Chromosome studies were performed on three independently derived tumor cell lines established from carcinomas induced in nude mice after innoculation of SV40 immortalized human uroepithelial cells that had been treated with methylcholanthrene. Tumor 1 was an undifferentiated carcinoma, while tumors 7 and 9 were both squamous carcinomas. After six to eight passages in vitro the tumor cells were each reinoculated into other nude mice to yield secondary tumors (1.1 and 7.1). Chromosome studies on both primary and secondary tumors demonstrated the same distinctive chromosome markers. Tumors 1 and 1.1 shared the same histopathology in addition to the same modal chromosome number and identical chromosomal duplications and deficiencies; the same was true of tumors 7 and 7.1. Tumor 9, which did not yield a secondary tumor, nevertheless showed the same chromosome pattern in different passages. The stability of the characteristic marker chromosomes in the three tumor cell lines distinguishes these malignant lines from the nonmalignant SV40 transformed parent line from which the three tumors derived because the parent line was characterized by extreme marker instability. This suggests that the stable marker chromosomes that characterize the tumor cell lines may be critical for their tumorigenicity, and that evolution of an adaptive neoplastic genome may select for cytogenetic stability as long as there are no new selective pressures.

Animals↗