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Genetic convergence during serial in vitro passage of a polyclonal squamous cell carcinoma.

A cell line was established from an in situ squamous cell carcinoma of the skin (Bowen's disease), and its in vitro karyotypic evolution was cytogenetically analyzed. Initially, considerable genetic heterogeneity was evident. Nine cytogenetically abnormal clones, eight of which were apparently unrelated, were found among the 83 metaphases analyzed from the primary culture and the first passage. With increasing time in culture this complexity was reduced, so that a single clone dominated passages 7-11. The clone that emerged from this genetic convergence had a t(12;17)(p13;q21) as the sole abnormality. Our findings indicate that the cytogenetic multiclonality that has been repeatedly detected in short-term cultures of squamous cell carcinomas is not caused by the in vitro conditions. Instead, the principles of Darwinian selection apply: the altered, but stable, selection pressure facing a newly established and initially multiclonal cell line will lead to a reduction of genetic heterogeneity until the one clone that now has the proliferative advantage outgrows the other subpopulations.

Biological Evolution↗

Population prehistory of east Asia and the Pacific as viewed from craniofacial morphology: the basic populations in east Asia, VII.

Distance analyses were applied to 11 craniofacial measurements recorded in samples from East and Southeast Asia, Australia, Melanesia, Polynesia, and Micronesia for the purpose of assessing the biological affinities and possible origins of these populations. A clear separation between Australomelanesians and other populations from East and Southeast Asia and the Pacific is evident. The craniofacial variations suggest that the generalized Asian populations (Negritos, Dayaks, Lesser Sunda Islands, etc.) represent at least part of the morphological background of not only the majority of present Southeast Asians, but also the Neolithic Jomon people and their lineage in Japan, Polynesians, and western Micronesians. The original craniofacial features of Southeast Asians may have occurred as the result of convergent microevolution due to similar environmental conditions such as tropical rain forest. This supports the local-evolution hypothesis for modern Southeast Asian craniofacial features.

Adult↗

Interspecific comparison of Drosophila serendipity delta and beta: multimodular structure of these C2H2 zinc finger proteins.

The Drosophila serendipity (sry) beta and delta genes, which resulted from a gene duplication event, provide an interesting model for the evolutionary diversification in structure and function of C2H2 zinc finger proteins. We examined here the divergence of the sry beta and delta proteins over an estimated period of 45 million years by comparing their predicted sequences in D. melanogaster, D. pseudoobscura, and D. subobscura. Between orthologs, i.e., pairs of either sry beta or sry delta, the NH2-proximal region delineated by pairs of C-X2-C motifs and the DNA-binding finger domain are highly conserved. Sequence conservation operates over the entire finger domain, including the links separating adjacent fingers, even though each has a unique sequence different from the widespread TGEKP motif. In contrast, the sequence of the central acidic region has extensively diverged and differs between species in the number of amino acids, probably because of slippage-driven mutations. The NH2-terminal region and fingers 1, 5, and 6 differentiate the sry beta and delta proteins while zinc fingers 2, 3, and 4 are virtually identical in these two paralogs. A nuclear localization signal of the SV40T antigen type, preceded by a potential CKII phosphorylation regulatory site, is conserved in sry delta but not found in sry beta. The interspecific conserved regions correlate well with the positions of zygotic lethal mutations in the D. melanogaster sry delta protein. Furthermore, P-element transformation experiments show that a transgenic copy of the D. pseudoobscura sry delta gene rescues the sry delta mutant phenotype. Convergence of genetic and structural data on the sry proteins supports a multimodular function and mode of evolution of these C2H2 finger proteins.

Amino Acid Sequence↗

Statistical evidence for a more than 800-million-year-old evolutionarily conserved genomic region in our genome.

Identification of conserved genomic regions between different species is crucial for the reconstruction of their last common ancestor. Indeed, such regions of conservation in today's species (if not due to chance) may either constitute stigmata of an ancestrally conserved region or result from a series of independent convergent events. The more phylogenetically distant the compared species are, the more we expect rearrangements and thus difficulties in finding regions of conservation. Here we decipher with strong evidence conserved genomic regions between vertebrates (human and zebrafish) and arthropods (Drosophila and Anopheles). This work includes a robust phylogenetic analysis in conjunction with a stringent statistical testing that allowed the significant rejection of a "by chance" conservation hypothesis. The conservation of gene clusters across four different species from two phylogenetically distant groups makes the hypothesis of an ancestral conservation more likely and parsimonious than the hypothesis of individual convergent events. This result shows that, in spite of more than 800 million years of divergence and evolution from their last common ancestor, we can still reveal stigmata of conservation between all these species. The last common ancestor of zebrafish, human, Drosophila, and Anopheles is the common ancestor of all protostomes and deuterostomes known as "Urbilateria." This study reveals clusters of probably ancestrally conserved genes and constitutes an advance toward the reconstruction of the genome of Urbilateria. Thus this work allows a better understanding of the evolutionary history of metazoan genomes, including our genome.

Animals↗

Advancing cancer detection and treatment using longitudinal routine clinical data.

Cancer management remains fragmented across its continuum, from late-stage diagnosis and salvage therapies to non-personalized surveillance. Here, we present Oncoformer, a unified multimodal transformer model trained on the China Oncology Multimodal Prediction and Surveillance Study (COMPASS) cohort (3.67 million individuals, 17.7 million clinical visits) and validated on independent external cohorts, including the UK Biobank. Oncoformer integrates longitudinal electronic health records with chest X-ray imaging to address multiple clinical tasks: pan-cancer diagnosis (area under the receiver operating characteristic curve [AUROC] = 0.956), future cancer prediction up to 1 year before diagnosis (AUROC = 0.869), tumor stage inference (mean AUROC > 0.90), patient-specific treatment-response forecasting, and recurrence-free survival stratification across ten cancer types (all p < 0.01). Staging predictions were independently validated against postoperative pathological endpoints and shown to converge on core cancer genomic pathways. By translating routine clinical data into a dynamic view of cancer evolution, Oncoformer provides a framework for risk-informed cancer prediction and treatment stratification using routine clinical data.

Humans↗

The ellipsis of prognosis in modern medical thought.

Contemporary textbooks of internal medicine give scant attention to the prognosis of diseases. Has this always been the case? If not, when and why did prognosis come to be de-emphasized? Using a highly regarded, standard medical textbook initially authored by William Osler, The Principles and Practice of Medicine, I performed qualitative and quantitative content analysis of entries regarding lobar pneumonia in selected editions published between 1892 and 1988, with special attention to the period between 1892 and 1947. I chose lobar pneumonia because it was a leading cause of death throughout this period and because it is recognizable across time, thus making it possible to follow the evolution in clinical thinking about prognosis while holding constant the diagnosis. I argue that two powerful forces converged to lead to the ellipsis of prognosis: (1) the emergence of effective therapy, and (2) a fundamental change in the cognitive basis of medicine. With respect to the former, I show that there is a complementary, inverse relationship between the clinical acts of prognostication and therapy; as one increases in salience in the management of a disease, the other decreases. With respect to the latter, I argue that the particular clinical facts deemed to be important about a patient's case have shifted over time, and I explore changes in the clinical and cognitive foundations of physicians' estimation of patients' prognoses-in particular, "symptoms" and "complications." I conclude that, concurrent with a shift in clinical thought from an individual-based to a diagnosis-based conceptualization of disease, prognosis came to be seen as intrinsic to diagnosis and therapy, and explicit attention to prognosis consequently diminished.

Curriculum↗

Informatics and medical libraries: changing needs and changing roles.

Medical librarians play a crucial role in the evolution of institutional information policy. As information professionals, they share many similarities with their medical informatics counterparts. Both groups emphasize information delivery to the point of decision making; both groups serve as curators of institutional knowledge bases. If the term "publication" encompasses the delivery of clinical information relevant to individuals or populations, both librarians and medical informaticians have an immediate interest in the nature of biomedical publishing, particularly in areas of intellectual ownership, confidentiality, distribution, and access. Both groups also have been early leaders in applying information technology to solve pressing knowledge-management problems, and both groups have a strong commitment to educating colleagues in the effective use of information. Although the challenges faced by librarians and medical informaticians are sometimes different, the evolution of information technology and new forms of biomedical communication suggest that there is now a greater convergence between the two disciplines.

Artificial Intelligence↗

Multiple gene evidence for expansion of extant penguins out of Antarctica due to global cooling.

Classic problems in historical biogeography are where did penguins originate, and why are such mobile birds restricted to the Southern Hemisphere? Competing hypotheses posit they arose in tropical-warm temperate waters, species-diverse cool temperate regions, or in Gondwanaland approximately 100 mya when it was further north. To test these hypotheses we constructed a strongly supported phylogeny of extant penguins from 5851 bp of mitochondrial and nuclear DNA. Using Bayesian inference of ancestral areas we show that an Antarctic origin of extant taxa is highly likely, and that more derived taxa occur in lower latitudes. Molecular dating estimated penguins originated about 71 million years ago in Gondwanaland when it was further south and cooler. Moreover, extant taxa are inferred to have originated in the Eocene, coincident with the extinction of the larger-bodied fossil taxa as global climate cooled. We hypothesize that, as Antarctica became ice-encrusted, modern penguins expanded via the circumpolar current to oceanic islands within the Antarctic Convergence, and later to the southern continents. Thus, global cooling has had a major impact on penguin evolution, as it has on vertebrates generally. Penguins only reached cooler tropical waters in the Galapagos about 4 mya, and have not crossed the equatorial thermal barrier.

Animal Migration↗

Sequence analysis of the mouse RAG locus intergenic region.

The recombination activating genes RAG-1 and RAG-2 are highly conserved throughout evolution and are necessary and essential for the DNA rearrangement of antigen-receptor gene segments. These convergently transcribed genes are expressed primarily by developing B and T lineage cells. In addition, recent data suggest that the RAG locus can be reactivated in mouse germinal center B cells. Despite these well-defined patterns of expression, little is known about mechanism(s) regulating transcription of the RAG locus. Experiments with a mouse fibroblast line stably transfected with a genomic fragment of the RAG locus suggest that the intergenic region between RAG-1 and RAG-2 may contain information modulating RAG transcription. In order to begin testing this hypothesis, we have sequenced the 7.0-kb RAG intergenic region of the mouse. The sequence did not contain open reading frames larger than 60 amino acids. Analysis with GCG software identified several potential transcription-factor binding sequences within this region. Many of these are associated with transcriptional regulation of the Ig locus.

3' Untranslated Regions↗

Chronicle of advocacy to increase AAPI focused objectives in Healthy People 2010: implications for tobacco-related data and research.

OBJECTIVES: The objectives of this chronicle is to illustrate key components of health polocy advocacy in increasing data availability and research for Asian Americans and Pacific Islanders (AAPIs). METHODS: Through the examination of the evolution of AAPI data in Healthy People 2000 to Healthy People 2010, this chronicle cites parallel and convergent advocacy by AAPI health advocates and tobacco advocates with key external factors that resulted in an increase in AAPI data included in Healthy People 2010. FINDINGS: In Healthy People 2000, there were eight objectives focusing on AAPIs. In Healthy People 2010, 98 objectives included some data for AAPIs and 120 objectives provided categorical reasons why AAPI data were not available. In Healthy People 2010, there was only one objective on tobacco use focusing on AAPIs. Healthy People 2010 includes 11 tobacco use objectives with either AAPI data or categorical reasons why the data were not available. Understanding why AAPI data are not available can direct advocacy efforts. CONCLUSIONS: The AAPI data improvements in Healthy People 2010 have provided useful information on data availability and strategy for data development at the national level. At the same time, the limitations of the national data (lack of AAPI ethnic specific data, data collected only in English) calls for more appropriate data collection and research at the local and regional level.

Asian↗

Development aspects of migration in third world settings: a simulation, with implications for urbanization.

A simulation of the interrelationships between development and migration in developing countries is presented. "Development is represented as the diffusion of demographic transition, employment opportunities, and formal and communication channels, which in turn affect informal communications and the overall economic base. The simulation falls within the genre of neoclassical development models, but, unlike many, explicitly explores the long-run aspects of landscape evolution." The results generally "conform with expectations hypothesized in earlier research, including phenomena such as polarization reversal, converging regional disparities, and low-level equilibrium traps at small remote places where continual resource drain thwarts the agglomeration economies necessary for sustained growth. [The authors] also find that the initial urban system configuration has little effect on the final configuration, and that only urban size diseconomies are likely to alter significantly the size, spatial distribution, and spatial characteristics of the urban system."

Demography↗

Molecular evidence regarding the origin of echolocation and flight in bats.

Bats (order Chiroptera) are one of the few orders of mammals that echolocate and the only group with the capacity for powered flight. The order is subdivided into Microchiroptera and Megachiroptera, with an array of characteristics defining each group, including complex laryngeal echolocation systems in microbats and enhanced visual acuity in megabats. The respective monophylies of the two suborders have been tacitly assumed, although microbat monophyly is uncorroborated by molecular data. Here we present a phylogenetic analysis of bat relationships using DNA sequence data from four nuclear genes and three mitochondrial genes (total of 8,230 base pairs), indicating that microbat families in the superfamily Rhinolophoidea are more closely related to megabats than they are to other microbats. This implies that echolocation systems either evolved independently in rhinolophoids and other microbats or were lost in the evolution of megabats. Our data also reject flying lemur (order Dermoptera) as the bat sister group, indicating that presumed shared derived characters for flying lemurs and bats are convergent features that evolved in association with gliding and flight, respectively.

Animals↗

Differential expression of orthologous Dlx genes in zebrafish and mice: implications for the evolution of the Dlx homeobox gene family.

Dlx homeobox genes of vertebrates are often organised as physically linked pairs in which the two genes are transcribed convergently (tail-to-tail arrangement). Three such Dlx pairs have been found in mouse, human, and zebrafish and are thought to have originated from the duplication of an ancestral gene pair. These pairs include Dlx1/Dlx2, Dlx7/Dlx3, and Dlx6/Dlx5 (the zebrafish orthologue of Dlx5 is named dlx4). Expression patterns of physically linked Dlx genes overlap extensively. Furthermore, orthologous Dlx genes often show highly similar expression patterns. We analysed Dlx expression during the gastrula and early somitogenesis of the mouse and zebrafish. It was found that expression of the mouse Dlx6 gene takes place in the rostral ectoderm and presumptive olfactory and otic placodes with patterns similar to the previously reported expression of the physically linked Dlx5 gene. However, we observed only very weak expression of the mouse Dlx3 gene at the same stage. This contrasts with the expression of dlx genes in zebrafish where dlx3 and dlx7, but not dlx4 and dlx6 are expressed during gastrulation in the rostral ectoderm and presumptive placodes. Thus, Dlx expression patterns at early stages are better conserved between paralogous pairs of physically linked genes than between orthologous pairs. This suggests that early expression of Dlx genes existed prior to the duplications that led to the multiple pairs of physically linked genes but was differentially conserved in different paralogs in zebrafish and mice.

Animals↗

The evolution of the human mind and logic--mathematics structures.

The evolution of the human mind is discussed based on: (i) the fact that living beings interchange matter, energy and information with their environment, (ii) an ontological interpretation of the "reality" of the quantum world, of which logic-mathematics structures are considered constitutive parts, (iii) recent theories according to which living beings are considered as dynamic complex systems organized by information, and (iv) the fact that the evolution of living beings is guided by information about the environment and by intrinsic information on living systems (auto-organization). Assuming the evolution of vision as a model we observe that the driving forces that directed the evolution of the eyes, as dynamic complex systems, are the information about the environment supplied by sunlight and the intrinsic information-gaining mechanism of living organisms. Thus, there exists a convergence toward a visual system with the greatest ability to obtain light information, like the human eye, and also a divergence that leads to the development of specific qualities in some species. As in the case of vision the evolution of the human mind-brain cannot be a consequence of factors unrelated to the object of its own functioning. The human mind was structured for the acquisition from reality of the logic-mathematics structures that underlie the whole universe and consequently of an internal representation of the external world and of its own self. Thus, these structures are, together with the intrinsic capacity for auto-organization of the human brain, the predominant driving force of the human mind evolution. Both factors are complementary.

Biological Evolution↗

Remark on the (non)convergence of ensemble densities in dynamical systems.

We consider a dynamical system with state space M, a smooth, compact subset of some R(n), and evolution given by T(t), x(t)=T(t)x, x in M; T(t) is invertible and the time t may be discrete, t in Z, T(t)=T(t), or continuous, t in R. Here we show that starting with a continuous positive initial probability density rho(x,0)>0, with respect to dx, the smooth volume measure induced on M by Lebesgue measure on R(n), the expectation value of logrho(x,t), with respect to any stationary (i.e., time invariant) measure nu(dx), is linear in t, nu(logrho(x,t))=nu(logrho(x,0))+Kt. K depends only on nu and vanishes when nu is absolutely continuous with respect to dx.(c) 1998 American Institute of Physics.

Journal Article↗

Experimental evolution recapitulates natural evolution.

Genomes of the closely related bacteriophages phiX174 and S13 are 5386 bases long and differ at 114 nucleotides, affecting 28 amino acids. Both parental phages were adapted to laboratory culture conditions in replicate lineages and analysed for nucleotide changes that accumulated experimentally Of the 126 experimental substitutions, 90% encoded amino-acid changes, and 62% of the substitutions occurred in parallel in more than one experimental line. Furthermore, missense changes at 12 of the experimental sites were at residues differing between the parental phages; in ten cases the phiX174 experimental lineages were convergent with the S13 parent, or vice versa, at both the nucleotide and amino-acid levels. Convergence at a site was even obtained in both directions in three cases. These results point to a limited number of pathways taken during evolution in these viruses, and also raise the possibility that much of the amino-acid variation in the natural evolution of these viruses has been selected.

Bacteriophage phi X 174↗

Evolution and development of time coding systems.

Precise temporal coding is a hallmark of both the electrosensory and auditory systems. Selective pressures to improve accuracy or encode more rapid changes have produced a suite of convergent physiological and morphological features that contribute to temporal coding. Comparative studies of temporal coding can also point to shared computational strategies, and suggest how selection might act to improve coding.

Animals↗