Cancer cell lines show high heritability for motility but not generation time

Tumour evolution depends on heritable differences between cells in traits affecting cell survival or replication. It is well established that cancer cells are genetically and phenotypically heterogeneous; however, the extent to which this phenotypic variation is heritable is far less well explored. Here, we estimate the broad-sense heritability (H2) of two cell traits related to cancer hallmarks––cell motility and generation time––within populations of four cancer cell lines in vitro and find that motility is strongly heritable. This heritability is stable across multiple cell generations, with heritability values at the high end of those measured for a range of traits in natural populations of animals or plants. These findings confirm a central assumption of cancer evolution, provide a first quantification of the evolvability of key traits in cancer cells and indicate that there is ample raw material for experimental evolution in cancer cell lines. Generation time, a trait directly affecting cell fitness, shows substantially lower values of heritability than cell speed, consistent with its having been under directional selection removing heritable variation

Heart failure and sudden cardiac death in heritable thoracic aortic disease caused by pathogenic variants in the SMAD3 gene

Background: Predominant cardiovascular manifestations in the spectrum of Heritable Thoracic Aortic Disease include by default aortic root aneurysms- and dissections, which may be associated with aortic valve disease. Mitral- and tricuspid valve prolapse are other commonly recognized features. Myocardial disease, characterized by heart failure and/or malignant arrhythmias has been reported in humans and in animal models harboring pathogenic variants in the Fibrillin1 gene. Methods: Description of clinical history of three cases from one family in Ghent (Belgium) and one family in St. Louis (US). Results: We report on three cases from two families presenting end-stage heart failure (in two) and lethal arrhythmias associated with moderate left ventricular dilatation (in one). All three cases harbor a pathogenic variant in the SMAD3 gene, known to cause aneurysm osteoarthritis syndrome, Loeys-Dietz syndrome type 3 or isolated Heritable Thoracic Aortic Disease. Conclusions: These unusual presentations warrant awareness for myocardial disease in patients harboring pathogenic variants in genes causing Heritable Thoracic Aortic Disease and indicate the need for prospective studies in larger cohorts

TERC polymorphisms are associated both with susceptibility to colorectal cancer and with longer telomeres.

Shorter telomeres have been associated with increased risk of malignancy, including colorectal cancer (CRC). Telomere length is heritable and may be an intermediate phenotype linked to genetic susceptibility to CRC

On Fodor on Darwin on Evolution

Jerry Fodor argues that Darwin was wrong about "natural selection" because (1) it is only a tautology rather than a scientific law that can support counterfactuals ("If X had happened, Y would have happened") and because (2) only minds can select. Hence Darwin's analogy with "artificial selection" by animal breeders was misleading and evolutionary explanation is nothing but post-hoc historical narrative. I argue that Darwin was right on all counts. Until Darwin's "tautology," it had been believed that either (a) God had created all organisms as they are, or (b) organisms had always been as they are. Darwin revealed instead that (c) organisms have heritable traits that evolved across time through random variation, with survival and reproduction in (changing) environments determining (mindlessly) which variants were successfully transmitted to the next generation. This not only provided the (true) alternative (c), but also the methodology for investigating which traits had been adaptive, how and why; it also led to the discovery of the genetic mechanism of the encoding, variation and evolution of heritable traits. Fodor also draws erroneous conclusions from the analogy between Darwinian evolution and Skinnerian reinforcement learning. Fodor’s skepticism about both evolution and learning may be motivated by an overgeneralization of Chomsky’s “poverty of the stimulus argument” -- from the origin of Universal Grammar (UG) to the origin of the “concepts” underlying word meaning, which, Fodor thinks, must be “endogenous,” rather than evolved or learned

Cultural replication and microbial evolution

The aim of this paper is to argue that cultural evolution is in many ways much more similar to microbial than to macrobial biological evolution. As a result, we are better off using microbial evolution as the model of cultural evolution. And this shift from macrobial to microbial entails adjusting the theoretical models we can use for explaining cultural evolution

Targeted DNA demethylation of the Arabidopsis genome using the human TET1 catalytic domain.

DNA methylation is an important epigenetic modification involved in gene regulation and transposable element silencing. Changes in DNA methylation can be heritable and, thus, can lead to the formation of stable epialleles. A well-characterized example of a stable epiallele in plants is fwa, which consists of the loss of DNA cytosine methylation (5mC) in the promoter of the FLOWERING WAGENINGEN (FWA) gene, causing up-regulation of FWA and a heritable late-flowering phenotype. Here we demonstrate that a fusion between the catalytic domain of the human demethylase TEN-ELEVEN TRANSLOCATION1 (TET1cd) and an artificial zinc finger (ZF) designed to target the FWA promoter can cause highly efficient targeted demethylation, FWA up-regulation, and a heritable late-flowering phenotype. Additional ZF-TET1cd fusions designed to target methylated regions of the CACTA1 transposon also caused targeted demethylation and changes in expression. Finally, we have developed a CRISPR/dCas9-based targeted demethylation system using the TET1cd and a modified SunTag system. Similar to the ZF-TET1cd fusions, the SunTag-TET1cd system is able to target demethylation and activate gene expression when directed to the FWA or CACTA1 loci. Our study provides tools for targeted removal of 5mC at specific loci in the genome with high specificity and minimal off-target effects. These tools provide the opportunity to develop new epialleles for traits of interest, and to reactivate expression of previously silenced genes, transgenes, or transposons

Heritability of geographic range sizes revisited : a reply to Hunt et al.

Hunt et al.(2005) revisit the issue of range size heritability following our recent article on this topic (Webb and Gaston 2003). In that article, we showed that the range sizes of closely related species tend to be highly dissimilar and argued that this provided evidence to counter Jablonski’s (1987) claim that range size was a heritable species-level trait. Hunt et al. do not dispute the fact that the species pairs that we examined have highly asymmetric range sizes; however, they claim that the statistical technique that we used to assess the significance of this asymmetry is flawed. They then return to correlation analyses to support their assertion that range size is indeed heritable. While some points of technical interest are raised, we disagree with their conclusions and feel that the analyses that they present provide little insight into the ultimate questions

Female reproductive strategy predicts preferences for sexual dimorphism in male faces

The aim of the current studies was to test an assumption that variation in female preferences for sexually dimorphic male facial characteristics reflects strategic optimisation of investment in offspring. A negative relationship was predicted between ideal number of children and preferences for masculine male face shapes, as the benefits of securing paternal investment should outweigh the benefits of securing good genes as the costs of raising offspring increase. In Study 1 desired number of children and preferences for masculine face shapes were compared in a sample of female students. In study 2, the prediction was tested in a sample with a wider age profile while controlling for relationship status. Preferences for explicit partner characteristics were also assessed. The prediction was supported: women who desired a higher number of children preferred more feminine male face shapes and ranked cues to investment of parental care over cues to immunocompetence in a partner more highly than those who desired fewer children. Results indicate that female mate preferences vary with reproductive strategy and support assumptions that preferences for feminine male faces reflect preferences for “good dads”