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Divergent Book Download Pdf 376 PATCHED



The most distinctive and prominent feature of behavioral modernity identified by paleoanthropologists and archeologists is what psychologists have described as creativity, particularly the achievements and personality traits of highly creative people. Creativity can be succinctly defined as the use of imagination or original ideas to achieve valued goals [34, 35], and is a multifaceted phenomenon that can be assessed in terms of particular aspects of intelligence and/or particular aspects of personality [36,37,38]. The psychometric tests of the creative aspects of intelligence were developed by Guilford and Torrance to measure aspects of divergent thinking in verbal and pictorial tasks. Divergent thinking is an innovative way of solving problems by exploring many possible solutions, making spontaneous intuitive connections among what are conventionally regarded as disparate phenomena, while tolerating some ambiguity [39]. Divergent thinking typically occurs in states of restful and playful self-aware evaluation of internal thoughts and images, such as mind-wandering in the default mode, flow, free association, day-dreaming, or contemplation [37, 40,41,42], which depends on activation of the medial prefrontal cortex for evaluation of internal stimuli as a core component of the self-awareness network [43, 44]. In contrast, convergent thinking follows a logical sequence of inferences to arrive at a single solution with certainty; it depends on the lateral prefrontal and parietal cortices, which are core components of the executive self-control network that supports purposeful use of symbols and intentional inhibition of externally triggered impulses [19, 45, 46].




divergent book download pdf 376



The features used to measure divergent thinking include originality (inventive and imaginative thoughts), flexibility (ability to move from one conceptual field to another), fluency (free-flow of many relevant ideas and responses), elaboration (many vivid, specific details), a high degree of abstraction, and persistence despite uncertainty [39, 47, 48]. Divergent thinking tests developed by Guilford and Torrance are the most widely used tests of creative intellectual functioning because they are strongly predictive of creative achievement and problem-solving ability in everyday life [38, 47, 48].


In addition to its cognitive properties, divergent thinking involves relaxed states of intuitive awareness that are also characterized by physical spontaneity, cheerful affect, playfulness, and sociability [40, 49, 50], which can be quantified in terms of personality characteristics. Personality refers to the way an individual learns to shape and adapt to an ever-changing internal and external environment [51].


Two gerbil species, sand rat (Psammomys obesus) and Mongolian jird (Meriones unguiculatus), can become obese and show signs of metabolic dysregulation when maintained on standard laboratory diets. The genetic basis of this phenotype is unknown. Recently, genome sequencing has uncovered very unusual regions of high guanine and cytosine (GC) content scattered across the sand rat genome, most likely generated by extreme and localized biased gene conversion. A key pancreatic transcription factor PDX1 is encoded by a gene in the most extreme GC-rich region, is remarkably divergent and exhibits altered biochemical properties. Here, we ask if gerbils have proteins in addition to PDX1 that are aberrantly divergent in amino acid sequence, whether they have also become divergent due to GC-biased nucleotide changes, and whether these proteins could plausibly be connected to metabolic dysfunction exhibited by gerbils.


To test whether the results of this analysis are applicable to other gerbil species, we compared Sneath values of 10,069 Mongolian jird genes to their murid orthologues, finding 41 aberrantly divergent genes in the Mongolian jird (Additional file 2). This number is lower than sand rat partly due to incompleteness of the Mongolian jird genome assembly. Average gerbil Sneath values were also compared to average murid Sneath values (Additional file 1: Fig. S4).


We then used a branch-site test to identify sand rat proteins that show evidence of positive selection at specific residues [36]. We used an implementation of this test that incorporates codon substitution rate variation and thereby controls for variation in the synonymous substitution rate caused by factors such as GC-biased gene conversion [37]. We identified 13 aberrantly divergent sand rat proteins with evidence of positive selection at specific residues (Additional file 1: Fig. S7B, S8). These include one of the positively selected proteins identified by the branch test model, TEX37, and six of the 26 proteins with an outlying dSws. These results show that positive selection has contributed to the evolution of some aberrantly divergent gerbil proteins but is not the major force leading to most of the observed extreme amino acid differences.


We asked if the evolution of aberrantly divergent proteins, driven primarily by elevated mutational and gBGC processes, could have phenotypic consequences for gerbils. Specifically, we wished to test if the evolution of divergent gerbil genes could be associated with the type 2 diabetes-prone phenotype observed in sand rats and Mongolian jirds.


To search for possible associations between aberrant protein divergence and propensity to type 2 diabetes, we took a candidate gene approach. Specifically, we asked if any of the proteins showing extreme relative divergence in gerbils have been linked to dietary metabolism in other species. We note that amongst the top 10 most aberrantly divergent sand rat proteins, four are clearly associated with lipid or carbohydrate metabolism. The genes encoding these are all located in the extreme GC-rich region of sand rat genome (Table 1). These four proteins are the previously discussed PDX1 transcription factor, plus MEDAG (Mesenteric Estrogen Dependent Adipogenesis), INSR (Insulin Receptor) and SPP1 (Secreted Phosphoprotein 1 or osteopontin). In Fig. 5, we show protein sequence alignments of these four proteins to highlight some of the highly unusual amino acid changes observed in sand rat and related gerbil species, compared to other mammals. In the PDX1 protein, there is a high degree of conservation across vertebrates of the hexapeptide domain (a cofactor binding domain) and the homeodomain (DNA-binding and sequence recognition domain), but extreme divergence in three gerbil species (Fig. 5a) [3, 5]. For INSR, a strong candidate for association with metabolic function, we find many amino acid changes unique to the gerbil lineage throughout the protein, although nearly all key amino acid sites previously associated with T2D in humans remained conserved (Fig. 5b). For MEDAG and SPP1, we also observe a number of gerbil-specific amino acid residues in mammal-conserved regions (Fig. 5c and d).


When unusual or divergent proteins are observed in some species and not others, this is generally thought to result from natural selection acting to adjust or optimize a protein for a new or modified function. The contributions of mutation rate variation and recombination frequency differences between species are easily overlooked. However, there is growing evidence that these genomic and chromosomal level processes can have dramatic effects on the way that genes and proteins evolve. In this study, we focus on two gerbil species that have unusual GC-rich regions scattered through their genome, where recombination-related processes are causing accumulation of G and C nucleotides [5]. Previous work showed that GC-biased substitutions in one of these regions caused deleterious amino acid changes in a sand rat protein, PDX1 [4]. Here we analyse the predicted proteomes of two gerbil species to identify proteins that are aberrantly divergent compared to other rodent species. We then test whether these proteins have become divergent because of association with GC-rich genomic regions and GC bias, rather than because of positive selection. In addition, we ask whether any of the aberrant proteins could be linked to physiological abnormalities observed in some gerbils.


Using the branch test, we detect signals of strong positive selection in only 3 out of 50 aberrantly divergent proteins (Additional file 2). These are TEX37 (Testis Expressed 37), SYCP2L (Synaptonemal Complex Protein 2 Like) and IL15 (Interleukin 15); they are not associated with GC bias nor located in GC-rich regions. TEX37 is predominantly expressed in the testis [38] while SYCP2L is mainly expressed in the ovary [39]. In addition, gene association studies report a correlation between SYCP2L variants and lipid metabolism, although the mechanism remains unknown [40, 41]. IL15 is a proinflammatory cytokine that activates T-cells and aberrant activity has been linked to destruction of pancreatic beta-cells in type 1 diabetes (T1D) [42, 43]. However, autoimmune destruction of β-cells has not been postulated as a cause of metabolic dysfunction in gerbils. In general, reproductive proteins and immunity-related proteins are under positive selection in many species [44, 45].


The two gerbil species focused on in this study have also been reported to become obese and exhibit metabolic abnormalities when maintained on a standard laboratory diet or a high fat diet, although not in the wild [23, 25, 49, 50]. For example, sand rat islet cells show more pancreatic β-cell damage compared to rat islets when exposed to high glucose concentrations, and even healthy sand rats on plant-based diets do not have a strong response to human insulin [51, 52]. Could these metabolic disorders be related to the accumulation of deleterious mutations in gerbils, driven by excessive biased gene conversion? We do not have direct evidence linking specific genetic changes with phenotype, but we argue there is a plausible connection. We highlight four aberrantly divergent gerbil proteins for which the human and mouse orthologues have been associated with dietary metabolism: PDX1, INSR, MEDAG and SPP1. In two cases, the human orthologues have been associated directly with type 2 diabetes or other metabolic diseases, and these associations can be tracked down to single amino acid substitutions or other small mutations. In gerbils we see dramatic amino acid change at multiple conserved sites. In the other two cases, functional studies in mouse or human indicate key roles in adipose tissue.


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