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PubMed1998

Understanding developmental psychopathology: how useful are evolutionary accounts?

OBJECTIVE: To consider the power of principles derived from evolutionary biology to explain the causes and determinants of some forms of child and adolescent mental disorders. METHOD: The authors reviewed the scientific literature for evolutionary mechanisms proposed to contribute to the pathogenesis of early-onset disorders. RESULTS: A diverse set of evolutionary mechanisms has been proposed. With the exception of certain genetically determined conditions, many of the proposed mechanisms have little empirical data to support them. One mechanism focuses on the vulnerabilities associated with conserved behavior patterns, such as separation anxiety and other alarm responses. These behavioral patterns are adaptive if they appear in some situations, but not in others. Other attractive theories include a co-optation of underlying neurobiology systems (substance abuse), environmental shifts (transformation of present day environments away from primeval environments), and evolutionary arms races as may occur in putative autoimmune disorders with neuropsychiatric sequelae. CONCLUSIONS: Evolutionary biology provides a potentially powerful framework for understanding disease pathogenesis in child psychiatry and should permit the integration of new knowledge from a broad range of scientific disciplines. Evolutionary explanations are typically population-based and fail to account for why a particular individual is disciplines. Evolutionary explanations are typically population-based and fail to account for why a particular individual is affected. Consequently, any adequate account of disease pathogenesis requires that environmental events that impinge on CNS development be considered. Finally, the empirical testing of specific theories may prove to be difficult if not impossible.

Adolescent↗
PubMed2004

ADVICE: Automated Detection and Validation of Interaction by Co-Evolution.

ADVICE (Automated Detection and Validation of Interaction by Co-Evolution) is a web tool for predicting and validating protein-protein interactions using the observed co-evolution between interacting proteins. Interacting proteins are known to share similar evolutionary histories since they undergo coordinated evolutionary changes to preserve interactions and functionalities. The web tool automates a commonly adopted methodology to quantify the similarities in proteins' evolutionary histories for postulating potential protein-protein interactions. ADVICE can also be used to validate experimental data against spurious protein interactions by identifying those that have few similarities in their evolutionary histories. The web tool accepts a list of protein sequences or sequence pairs as input and retrieves orthologous sequences to compute the similarities in the proteins' evolutionary histories. To facilitate hypothesis generation, detected co-evolved proteins can be visualized as a network at the website. ADVICE is available at http://advice.i2r.a-star.edu.sg.

Evolution, Molecular↗
PubMed2001

Perspective: the origin of flowering plants and their reproductive biology--a tale of two phylogenies.

Recently, two areas of plant phylogeny have developed in ways that could not have been anticipated, even a few years ago. Among extant seed plants, new phylogenetic hypotheses suggest that Gnetales, a group of nonflowering seed plants widely hypothesized to be the closest extant relatives of angiosperms, may be less closely related to angiosperms than was believed. In addition, recent phylogenetic analyses of angiosperms have, for the first time, clearly identified the earliest lineages of flowering plants: Amborella, Nymphaeales, and a clade that includes Illiciales/ Trimeniaceae/Austrobaileyaceae. Together, the new seed plant and angiosperm phylogenetic hypotheses have major implications for interpretation of homology and character evolution associated with the origin and early history of flowering plants. As an example of the complex and often unpredictable interplay of phylogenetic and comparative biology, we analyze the evolution of double fertilization, a process that forms a diploid embryo and a triploid endosperm, the embryo-nourishing tissue unique to flowering plants. We demonstrate how the new phylogenetic hypotheses for seed plants and angiosperms can significantly alter previous interpretations of evolutionary homology and firmly entrenched assumptions about what is synapomorphic of flowering plants. In the case of endosperm, a solution to the century-old question of its potential homology with an embryo or a female gametophyte (the haploid egg-producing generation within the life cycle of a seed plant) remains complex and elusive. Too little is known of the comparative reproductive biology of extant nonflowering seed plants (Gnetales, conifers, cycads, and Ginkgo) to analyze definitively the potential homology of endosperm with antecedent structures. Remarkably, the new angiosperm phylogenies reveal that a second fertilization event to yield a biparental endosperm, long assumed to be an important synapomorphy of flowering plants, cannot be conclusively resolved as ancestral for flowering plants. Although substantive progress has been made in the analysis of phylogenetic relationships of seed plants and angiosperms, these efforts have not been matched by comparable levels of activity in comparative biology. The consequence of inadequate comparative biological information in an age of phylogenetic biology is a severe limitation on the potential to reconstruct key evolutionary historical events.

Magnoliopsida↗
PubMed1999

Comparison of active conformations of the insectatachykinin/tachykinin and insect kinin/Tyr-W-MIF-1 neuropeptide family pairs.

A comparison of solution conformations of active, restricted-conformation analogues of two sequence-similar insect/vertebrate neuropeptide family pairs shed light on the potential existence of molecular evolutionary relationships. Analogues of the locustatachykinins and the mammalian tachykinin substance P, containing a sterically hindered Aib-NMePhe/Tyr residue block, share similar low-energy turn conformations incorporating a cis peptide bond. Conversely, restricted conformation analogues of the insect kinins and the mammalian opiate peptide Tyr-W-MIF-1, with near identical C-terminal tetrapeptide sequences, adopt different conformations. The insect kinins adopt a cisPro 1-4 beta-turn, in which the Phe1 is critical for bioactivity. Tyr-W-MIF-1 prefers a transPro 2-5 turn, and an additional N-terminal Phe severely inhibits mu-opiate receptor binding. Comparisons of the chemical/conformational requirements for receptor interaction are consistent with a distant evolutionary relationship between the insectatachykinins and tachykinins, but not between the insect kinins and Tyr-W-MIF-1. Therefore, analogues of the insect kinins with pest control potential can be readily designed to avoid mammalian interactions.

Amino Acid Sequence↗
PubMed2026

Beyond Morphology: Reframing Lymph-Node Metastasis Prediction Through Clonal Ecology-Decades-Long Genomic Instability and Polyclonal-to-Monoclonal Transitions as the Missing Dimension in Cancer.

Recent whole-genome, lineage-tracing, single-cell, and spatial studies have reshaped our understanding of tumor evolution, revealing that cancers can arise from polyclonal populations, undergo decades-long genomic instability before clinical detection, and progress through dynamic changes in subclonal composition, cellular state, and ecological organization. These findings challenge the assumption underlying morphology-based prediction models that metastatic risk can be inferred from static histological features alone. Here, we revisit lymph-node metastasis prediction in colorectal cancer through clonal ecology, integrating computational pathology with evolutionary oncology. Drawing on the subclonal switchboard model proposed in 2012 and subsequent artificial intelligence (AI)-enabled approaches for tracking dominant and dormant subclones, we synthesize evidence that metastatic potential reflects clonal ancestry, evolutionary timing, spatial niche architecture, cellular plasticity, intercellular interactions, dormancy, and treatment-driven shifts in subclonal fitness. We define five complementary methodological pillars for operationalizing clonal ecology: single-cell transcriptomics for resolving rare subclones, evolutionary trajectories, and adaptive cell states; lineage tracing and phylogenetics for reconstructing clonal ancestry and divergence; spatial transcriptomics and genomics for mapping subclonal geography and tumor-stromal-immune interactions; longitudinal liquid biopsy surveillance for monitoring residual disease, clonal turnover, and emerging resistance; and AI-enabled multimodal integration for connecting histopathology, genomics, spatial biology, and longitudinal data into predictive ecological-state models. Multiple-instance learning and pathology foundation models provide scalable computational foundations for evolution-aware prediction. Translationally, dormant subclones represent actionable reservoirs of recurrence. A longitudinal clinical and experimental study of KMT2A-rearranged acute myeloid leukemia further supports central predictions of the subclonal switchboard framework by demonstrating treatment-associated shifts in subclonal dominance, persistence of cryptic adaptive programs, and ecological rewiring during resistance and relapse. We propose clonal ecology as a measurable dimension for extending morphology-driven prediction toward integrative models that anticipate evolutionary transitions, identify therapeutic windows, and proactively constrain adaptive tumor ecosystems before resistant or metastatic subclones achieve clinical dominance.

Humans↗
PubMedDate not supplied

Structure-based phylogeny of class IIa tRNA synthetases in relation to an unusual biochemistry.

The available three-dimensional information for class II aminoacyl-tRNA synthetases has been used to generate sequence alignments that strictly adhere to the structural equivalencies between members of subclass IIa of these enzymes. The resulting alignments were used to study their phylogenetic relationships. In particular, the entire set of available sequences of prolyl-tRNA synthetases was analyzed in this way. In contrast to recent reports, we conclude that the evolutionary pattern of prolyl-tRNA synthetases does not obviously conform to the canonical phylogenetic distribution. The pattern found for these enzymes may be related to their biochemical characteristics. Our results indicate a potential relationship between the evolutionary pattern of prolyl-tRNA synthetases and the emergence of two enzymatically distinct forms of these proteins.

Amino Acid Sequence↗
PubMed1992

On the duty to protect: an evolutionary perspective.

Psychotherapists' duty to protect potential victims from their patients' violence has evolved in recent years toward a narrower set of obligations. This reformulation of the duty appears to us to be consistent with a sociobiological analysis of the reasonableness of compelled altruism. Altruistic behavior (e.g., rescuing a potential victim) takes place rarely in the animal world, and even among humans usually occurs only in situations in which reciprocity is likely. The Tarasoff-like duty to protect violates this sociobiological rule by requiring therapists to place the interests of an unknown victim over a known patient, and even to subordinate their own interests to the victim's. This has never been a socially tenable position. Psychotherapists appear to have escaped from this situation by avoiding potentially dangerous patients. The changes in the duty to protect have mitigated this dilemma, by moving the duty in a direction consistent with the evolutionary theory of altruism.

Adult↗
PubMed2003

Computational identification of protein coding potential of conserved sequence tags through cross-species evolutionary analysis.

The identification of conserved sequence tags (CSTs) through comparative genome analysis may reveal important regulatory elements involved in shaping the spatio-temporal expression of genetic information. It is well known that the most significant fraction of CSTs observed in human-mouse comparisons correspond to protein coding exons, due to their strong evolutionary constraints. As we still do not know the complete gene inventory of the human and mouse genomes it is of the utmost importance to establish if detected conserved sequences are genes or not. We propose here a simple algorithm that, based on the observation of the specific evolutionary dynamics of coding sequences, efficiently discriminates between coding and non-coding CSTs. The application of this method may help the validation of predicted genes, the prediction of alternative splicing patterns in known and unknown genes and the definition of a dictionary of non-coding regulatory elements.

Algorithms↗
PubMed2000

The PWWP domain: a potential protein-protein interaction domain in nuclear proteins influencing differentiation?

Upon characterization of WHSC1, a gene mapping to the Wolf-Hirschhorn syndrome critical region and at its C-terminus similar to the Drosophila ASH1/trithorax group proteins, we identified a novel protein domain designated PWWP domain. To gain insight into its structure, evolutionary conservation and its potential functional role, we performed database searches to identify other PWWP domain-containing proteins. We retrieved 39 proteins, and a multiple alignment shows that the domain spans some 70 amino acids. It is present in proteins of nuclear origin and plays a role in cell growth and differentiation. Due to its position, the composition of amino acids close to the PWWP motif and the pattern of other domains present, we hypothesize that the domain is involved in protein-protein interactions.

Amino Acid Motifs↗
PubMed2002

Divergence of mitochondrial dna is not corroborated by nuclear dna, morphology, or behavior in Drosophila simulans.

We ask whether the observed mitochondrial DNA (mtDNA) population subdivision of Drosophila simulans is indicative of organismal structure or of specific processes acting on the mitochondrial genome. Factors either intrinsic or extrinsic to the host genome may influence the evolutionary dynamics of mtDNA. Potential intrinsic factors include adaptation of the mitochondrial genome and of nucleomitochondrial gene complexes specific to the local environment. An extrinsic force that has been shown to influence mtDNA evolution in invertebrates is the bacterial endosymbiont Wolbachia. Evidence presented in this study suggests that mtDNA is not a good indicator of organismal subdivision in D. simulans. Furthermore, there is no evidence to suggest that Wolbachia causes any reduction in nuclear gene flow in this species. The observed differentiation in mtDNA is not corroborated by data from NADH: ubiquinone reductase 75kD subunit precursor or the Alcohol dehydrogenase-related loci, from the shape or size of the male genital arch, or from assortative premating behavior. We discuss these results in relation to a mitochondrial genetic species concept and the potential for Wolbachia-induced incompatibility to be a mechanism of speciation in insects. We conclude with an iterated appeal to include phylogenetic and statistical tests of neutrality as a supplement to phylogenetic and population genetic analyses when using mtDNA as an evolutionary marker.

Animals↗
PubMed2026

Spatiotemporal patterns of Rift Valley fever virus in Africa: a retrospective genomic epidemiology and phylodynamic modelling study.

BACKGROUND: Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing outbreaks in humans and ruminants across Africa and the Arabian Peninsula. Originally restricted to the Great Rift Valley, RVFV has expanded geographically, prompting its classification by WHO as a pathogen of pandemic potential. We investigated the evolutionary and spatial dynamics of RVFV across Africa. METHODS: We used genomic data generated at the International Livestock Research Institute Nairobi genomic laboratory (BioProject PRJNA1106221) and combined with publicly available datasets retrieved from the National Center for Biotechnology (NCBI) GenBank nucleotide database. In retrieving RVFV genome sequences from the NCBI GenBank, we applied the search terms "Rift Valley fever virus segment L AND 6404[SLEN]", "Rift Valley fever virus segment M AND 3885[SLEN]", and "Rift Valley fever virus segment S AND 1520:1690[SLEN]" for L (Large), M (Medium), and S (Small) segments, respectively. For sequences without additional spatiotemporal information, we searched PubMed to extract the associated sequence metadata. We performed molecular clock analysis, phylogenetic inference, phylodynamic modelling (continuous phylogeographic reconstruction), and landscape phylogeography on the three RVFV genome segments (L, M, and S). We aimed to assess evolutionary rates, dispersal patterns, and environmental drivers. Focus was placed on lineage C, the most widely distributed variant. FINDINGS: The global dataset used in this study consisted of large (n=236), medium (n=237), and small (n=247), which were further filtered to exclude potential reassortants and vaccine strains. Genome sequences retrieved from NCBI GenBank database comprised large (n=180), medium (n=184), and small (n=202). The genome sequences from retrospective human and livestock isolates comprised large (n=56), medium (n=53), and small (n=45) collected in Burundi (2018), Kenya (2007, 2018, 2019, 2021, and 2022), and Rwanda (2018 and 2022). Our dataset revealed that RVFV exhibited low overall genetic diversity. Lineage C, however, showed evidence of active evolution, with substitution rates ranging from 3·58 × 10-4 to 9·76 × 10-4 substitutions per site per year. This lineage probably originated in Zimbabwe in the mid-1970s and has since expanded across eastern and southern Africa. Phylogeographic reconstructions revealed rapid spread, with diffusion coefficients exceeding 50 000 km2 per year. INTERPRETATION: Lineage C appears capable of establishing endemic transmission in new regions, with ongoing diversification observed during interepidemic periods. These observations reinforce the value of continuous genomic surveillance, particularly during cryptic transmission phases when adaptive mutations might emerge. Although further evidence is needed, observed trends in climate variability and land-use change point to the potential benefit of targeted surveillance in settings that could be at increased risk, including urban centres and wetlands. FUNDING: This work was supported by the German Federal Ministry for Economic Cooperation and Development, the Rockefeller Foundation, and the Africa Centres for Disease Control and Prevention.

Rift Valley fever virus↗
PubMed2006

Inferring direct regulatory targets from expression and genome location analyses: a comparison of transcription factor deletion and overexpression.

BACKGROUND: Effects on gene expression due to environmental or genetic changes can be easily measured using microarrays. However, indirect effects on expression can be substantial. The indirect effects of a perturbation need to be distinguished from the direct effects if we are to understand the structure and behavior of regulatory networks. RESULTS: The most direct way to perturb a transcriptional network is to alter transcription factor activity. Here, for the first time, we compare expression changes and genomic binding in a simple regulon under conditions of both low and high transcription factor activity. Specifically, we assessed the effects on expression and binding due to deletion of the yeast LEU3 transcription factor gene and effects due to elevation of Leu3 activity. Leu3 activity was elevated through overexpression and the introduction of a mutation that renders the protein constitutively active. Genes that are bound and/or regulated by Leu3 under one or both conditions were characterized in terms of their functional annotations and their predicted potential to be bound by Leu3. We also assessed the evolutionary conservation of the predicted binding potential using a novel alignment-independent method. Both perturbations yield genes that are likely to be direct targets of Leu3, including most of the classically defined targets. Additional direct targets are identified by each of the methods. However, experimental and computational criteria suggest that most genes whose expression is affected by the Leu3 genotype are unlikely to be regulated by binding of the protein. CONCLUSION: Most genes that are differentially expressed by Leu3 are not direct targets despite the exceptional simplicity of the regulon, and the unusually direct nature of the perturbations investigated. These conclusions are reached through computational analyses that support and extend chromatin immunoprecipitation data on the identities of direct targets. These results have implications for the interpretation of expression experiments, especially in cases for which chromatin immunoprecipitation data are unavailable, incomplete, or ambiguous.

2-Isopropylmalate Synthase↗
PubMed2006

The genetic architecture of normal variation in human pigmentation: an evolutionary perspective and model.

Skin pigmentation varies substantially across human populations in a manner largely coincident with ultraviolet radiation intensity. This observation suggests that natural selection in response to sunlight is a major force in accounting for pigmentation variability. We review recent progress in identifying the genes controlling this variation with a particular focus on the trait's evolutionary past and the potential role of testing for signatures of selection in aiding the discovery of functionally important genes. We have analyzed SNP data from the International HapMap project in 77 pigmentation candidate genes for such signatures. On the basis of these results and other similar work, we provide a tentative three-population model (West Africa, East Asia and North Europe) of the evolutionary-genetic architecture of human pigmentation. These results suggest a complex evolutionary history, with selection acting on different gene targets at different times and places in the human past. Some candidate genes may have been selected in the ancestral human population, others in the 'out of Africa' proto European-Asian population, whereas most appear to have selectively evolved solely in either Europeans or East Asians separately despite the pigmentation similarities between these two populations. Selection signatures can provide important clues to aid gene discovery. However, these should be viewed as complements, rather than replacements of, functional studies including linkage and association analyses, which can directly refine our understanding of the trait.

Asian People↗
PubMedDate not supplied

Grandmothers and the evolution of human longevity.

Great apes, our closest living relatives, live longer and mature later than most other mammals and modern humans are even later-maturing and potentially longer-lived. Evolutionary life-history theory seeks to explain cross-species differences in these variables and the covariation between them. That provides the foundation for a hypothesis that a novel role for grandmothers underlies the shift from an ape-like ancestral pattern to one more like our own in the first widely successful members of genus Homo. This hypothesis links four distinctive features of human life histories: 1). our potential longevity, 2). our late maturity, 3). our midlife menopause, and 4). our early weaning with next offspring produced before the previous infant can feed itself. I discuss the problem, then, using modern humans and chimpanzees to represent, respectively, genus Homo and australopithecines, I focus on two corollaries of this grandmother hypothesis: 1). that ancestral age-specific fertility declines persisted in our genus, while 2). senescence in other aspects of physiological performance slowed down. The data are scanty but they illustrate similarities in age-specific fertility decline and differences in somatic durability that are consistent with the hypothesis that increased longevity in our genus is a legacy of the "reproductive" role of ancestral grandmothers.

Aging↗
PubMed2000

Evolutionary significance of myosin heavy chain heterogeneity in birds.

This article reviews the complexity, expression, genetics, regulation, function, and evolution of the avian myosin heavy chain (MyHC). The majority of pertinent studies thus far published have focussed on domestic chicken and, to a much lesser extent, Japanese quail. Where possible, information available about wild species has also been incorporated into this review. While studies of additional species might modify current interpretations, existing data suggest that some fundamental properties of myosin proteins and genes in birds are unique among higher vertebrates. We compare the characteristics of myosins in birds to those of mammals, and discuss potential molecular mechanisms and evolutionary forces that may explain how avian MyHCs acquired these properties.

Animals↗
PubMed2002

Cell-selfish modes of evolution and mutations directed after transcriptional bypass.

During transcription, prokaryotic and eukaryotic RNA polymerases bypass and misread (transcriptional mutagenesis) several classes of DNA lesions. For example, misreading of 8-OH-dG generates mRNAs containing G to T transversions. After translation, if the mutant protein briefly allowed the cell a growth-DNA replication advantage, then precocious DNA replication would bypass that unrepaired 8-OH-dG and misinsert dA opposite the directing DNA lesion with a higher probability than would be experienced for 8-OH-G lesions at other positions in otherwise identical neighboring cells. Such retromutations would have been tested for their imparted growth advantage as mRNA before they became heritable DNA mutations. The logical properties of a mode of evolution that utilizes directed-retromutagenesis were compared one by one with those of the standard neo-Darwinian mode. The retromutagenesis mode, while minimizing mutational load, is cell-selfish; fitness is for an immediate growth advantage rather than future reproductive potential. In prokaryotes, an evolutionary mode that involves standard Darwinian fitness testing of novel alleles in the genetic background of origin followed by clonal expansion also favors cell-selfish allele combinations when linkage disequilibrium is practiced. For metazoa and plants to have evolved organized tissues, cell-selfish modes of evolution represent systems-poisons that must be totally suppressed. The feedback loops that allow evolution to be cell-serving in prokaryotes are actively blocked in eukaryotes by traits that restrict fitness to future reproductive potential. These traits include (i) delay of fitness testing until after the mutation is made permanently heritable, (ii) diploidy to further delay fitness testing, (iii) segregation of somatic lines from germ lines, (iv) testing of novel alleles against randomized allele combinations constructed by obligate sex, and (v) obligate genetic death to insure that that the most basic systems unit of selfish allele combinatorial uniqueness is the species instead of the cell. The analyses indicate that modes of evolution in addition to our neo-Darwinian one could have existed utilizing known molecular mechanisms. The evolution of multicellularity was as much the discarding of old cell-selfish habits as the acquisition of new altruistic ones.

Alleles↗
PubMed1998

Characterization of the zebrafish tbx16 gene and evolution of the vertebrate T-box family.

We report on a new zebrafish T-box-containing gene, tbx16. It encodes a message that is first detected throughout the blastoderm soon after the initiation of zygotic gene expression. Following gastrulation, expression becomes restricted to paraxial mesoderm and later primarily to the developing tail bud. To gain an evolutionary prospective on the potential function of this gene, we have analyzed its phylogenetic relationships to known T-box genes from other species. Zebrafish tbx16 is likely orthologous to the chicken Tbx6L and Xenopus Xombi/Antipodean/Brat/VegT genes. Our analysis also shows that zebrafish tbx6 and mouse Tbx6 genes are paralogous to zebrafish tbx16. We present evidence which argues, that despite the same name and similar expression, zebrafish tbx6 and mouse Tbx6 genes are not orthologous to each other but instead represent relatively distant paralogs. The expression patterns of all genes are discussed in the light of their evolutionary relationships.

Amino Acid Sequence↗
PubMed2006

The genotypic complexity of evolved fault-tolerant and noise-robust circuits.

Noise and component failure is an increasingly difficult problem in modern electronic design. Bio-inspired techniques is one approach that is applied in an effort to solve such issues, motivated by the strong robustness and adaptivity often observed in nature. Circuits investigated herein are designed to be tolerant to faults or robust to noise, using an evolutionary algorithm. A major challenge is to improve the scalability of the approach. Earlier results have indicated that the evolved circuits may be suited for the application of artificial development, an approach to indirect mapping from genotype to phenotype that may improve scalability. Those observations were based on the genotypic complexity of evolved circuits. Herein, we measure the genotypic complexity of circuits evolved for tolerance to faults or noise, in order to uncover how that tolerance affects the complexity of the circuits. The complexity is analysed and discussed with regards to how it relates to the potential benefits to the evolutionary process of introducing an indirect genotype-phenotype mapping such as artificial development.

Algorithms↗