The Length of the Shortest Telomere as the Major Determinant of the Onset of Replicative Senescence

The absence of telomerase in many eukaryotes leads to the gradual shortening of telomeres, causing replicative senescence. In humans, this proliferation barrier constitutes a tumor suppressor mechanism and may be involved in cellular aging. Yet the heterogeneity of the senescence phenotype has hindered the understanding of its onset. Here we investigated the regulation of telomere length and its control of senescence heterogeneity. Because the length of the shortest telomeres can potentially regulate cell fate, we focus on their dynamics in Saccharomyces cerevisiae. We developed a stochastic model of telomere dynamics built on the protein-counting model, where an increasing number of protein-bound telomeric repeats shift telomeres into a nonextendable state by telomerase. Using numerical simulations, we found that the length of the shortest telomere is well separated from the length of the others, suggesting a prominent role in triggering senescence. We evaluated this possibility using classical genetic analyses of tetrads, combined with a quantitative and sensitive assay for senescence. In contrast to mitosis of telomerase-negative cells, which produces two cells with identical senescence onset, meiosis is able to segregate a determinant of senescence onset among the telomerase-negative spores. The frequency of such segregation is in accordance with this determinant being the length of the shortest telomere. Taken together, our results substantiate the length of the shortest telomere as being the key genetic marker determining senescence onset in S. cerevisiae.     

Utopia and Its Discontents: The Kibbutz and Its Historical Vicissitudes

Following an explication of "utopianism," this article describes the social and cultural systems of the original utopian communes comprising the Israeli kibbutz movement. It then describes the radical changes that have been made in those systems. After accounting for these changes, it assesses their implications for the utopian and cultural determinist theories of human nature.     

Epigenetic determinism in science and society

The epigenetic “revolution” in science cuts across many disciplines, and it is now one of the fastest-growing research areas in biology. Increasingly, claims are made that epigenetics research represents a move away from the genetic determinism that has been prominent both in biological research and in understandings of the impact of biology on society. We discuss to what extent an epigenetic framework actually supports these claims. We show that, in contrast to the received view, epigenetics research is often couched in language as deterministic as genetics research in both science and the popular press. We engage the rapidly emerging conversation about the impact of epigenetics on public discourse and scientific practice, and we contend that the notion of epigenetic determinism – or the belief that epigenetic mechanisms determine the expression of human traits and behaviors – matters for understandings of the influence of biology and society on population health.     

Emergentism as a default: Cancer as a problem of tissue organization

During the last fifty years the dominant stance in experimental biology has been reductionism. For the most part, research programs were based on the notion that genes were in ’the driver’s seat’ controlling the developmental program and determining normalcy and disease (genetic reductionism and genetic determinism). Philosophers were the first to realize that the belief that the Mendelian genes were reduced to DNA molecules was questionable. Soon after these pronouncements, experimental data confirmed their misgivings. The optimism of molecular biologists, fueled by early success in tackling relatively simple problems, has now been tempered by the difficulties found when attempting to understand complex biological problems. Here, we analyse experimental data that illustrate the shortcomings of this sort of reductionism. We also examine the prevailing paradigm in cancer research, the somatic mutation theory (SMT), the premises of which are: (i) cancer is derived from a single somatic cell that has accumulated multiple DNA mutations; (ii) the default state of cell proliferation in metazoa is quiescence; and (iii) cancer is a disease of cell proliferation caused by mutations in genes that control proliferation and the cell cycle. We challenge the notion that cancer is a cellular problem caused by mutated genes by assessing data gathered both from within the reductionist paradigm and from an alternative view that regards carcinogenesis as a developmental process gone awry. This alternative view, explored under the name of the tissue organization field theory (TOFT), is based on premises that place cancer in a different hierarchical level of complexity from that proposed by the SMT, namely: (i) carcinogenesis represents a problem of tissue organization comparable to organogenesis, and (ii) proliferation is the default state of all cells. We propose that the organicist view, in which the TOFT is based, is a good starting point from which to explore emergent phenomena. However, new theoretical concepts are needed in order to grapple with the apparent circular causality of complex biological phenomena in development and carcinogenesis.     

Living Precisely in Fin-de-Siècle Vienna

Vienna’s Institute of Experimental Biology, better known as the Vivarium, helped pioneer the quantification of experimental biology from 1903 to 1938. Among its noteable scientists were the director Hans Przibram and his brother Karl (a physicist), Paul Kammerer, Eugen Steinach, Paul Weiss, and Karl Frisch. The Vivarium’s scientists sought to derive laws describing the development of the individual organism and its relationship to the environment. Unlike other contemporary proponents of biological laws, however, these researchers created an explicitly anti-deterministic science. By “laws” they meant statistical regularities or “patterns.” They interpreted their experimental results in ways that forged a “third way” between determinism and pure spontaneity, aiming to capture the complexity of the interaction between the organism and its environment. This common feature of their research was made possible by the availability at the Vivarium of the latest in climate-control technology and of methods borrowed from statistical physics. The deeper roots of this search for a “third way” lay, I suggest, in the shared educational, social, and aesthetic experiences of the laboratory’s workers.     

‘Heritability’ of dispersal propensity in a patchy population

Although dispersal is often considered to be a plastic, condition-dependent trait with low heritability, growing evidence supports medium to high levels of dispersal heritability. Obtaining unbiased estimates of dispersal heritability in natural populations nevertheless remains crucial to understand the evolution of dispersal strategies and their population consequences. Here we show that dispersal propensity (i.e. the probability of dispersal between habitat patches) displays a significant heritability in the collared flycatcher Ficedula albicollis, as estimated by within-family resemblance when accounting for environmental factors. Offspring of dispersing mothers or fathers had a higher propensity to disperse to a new habitat patch themselves. The effect of parental dispersal status was additional to that of local habitat quality, as measured by local breeding population size and success, confirming previous results about condition-dependent dispersal in this population. The estimated levels of heritability varied between 0.30±0.07 and 0.47±0.10, depending on parent–offspring comparisons made and correcting for a significant assortative mating with respect to dispersal status. Siblings also displayed a significant resemblance in dispersal propensity. These results suggest that variation in between-patch natal dispersal in the collared flycatcher is partly genetically determined, and we discuss ways to quantify this genetic basis and its implications.     

The Cultural Politics of the Sociobiology Debate

The sociobiology debate, in the final quarterof the twentieth century, featured many of thesame issues disputed in the culture war in thehumanities during this same time period. This isevident from a study of the writings of EdwardO. Wilson, the best known of thesociobiologists, and from an examination ofboth the minutes of the meetings of theSociobiology Study Group (SSG) and the writingsof Stephen Jay Gould, the SSG's most prominentmember. Many critics of sociobiology,frequently radical scientists who were attachedto the lineage of the New Left, argued for thesame multicultural values promoted by radicalhumanities professors in this period.Conversely, liberal sociobiologists defendedthe universalist values of the liberals in the humanities.Those scholars whose work was important beforethe cultural revolution in the 1960s wereusually committed to a liberal universalismthat emphasized the similarity between people.Younger scholars, who took faculty positions inthe 1970s and after, were more likely to owe anallegiance to an ethnos-centered social visionthat valued identity politics. The strugglebetween these two agendas, more intellectualthan generational, was at the core of theculture wars both in the humanities and in thesciences. The sociobiology debate should beviewed in this light.     

The convergent evolution of snake‐like forms by divergent evolutionary pathways in squamate reptiles*

Convergent evolution of phenotypes is considered evidence that evolution is deterministic. Establishing if such convergent phenotypes arose through convergent evolutionary pathways is a stronger test of determinism. We studied the evolution of snake‐like body shapes in six clades of lizards, each containing species ranging from short‐bodied and pentadactyl to long‐bodied and limbless. We tested whether body shapes that evolved in each clade were convergent, and whether clades evolved snake‐like body shapes following convergent evolutionary pathways. Our analyses showed that indeed species with the same numbers of digits in each clade evolved convergent body shapes. We then compared evolutionary pathways among clades by considering patterns of evolutionary integration and shape of relationship among body parts, patterns of vertebral evolution, and models of digit evolution. We found that all clades elongated their bodies through the addition, not elongation, of vertebrae, and had similar patterns of integration. However, patterns of integration, the body parts that were related by a linear or a threshold model, and patterns of digit evolution differed among clades. These results showed that clades followed different evolutionary pathways. This suggests an important role of historical contingency as opposed to determinism in the convergent evolution of snake‐like body shapes.     

Biogeographical contingency and the evolution of tropical anchovies (genus Cetengraulis) from temperate anchovies (genus Engraulis)

Aim Similar regimes of selection in different geographical settings can deterministically produce similar adaptive morphologies. We tested the hypothesis that the evolutionary trajectories of fish in upwelling zones can be altered by biogeographic contingencies in the biological and physical environment. Location Eastern Pacific and western Atlantic oceans. Methods We estimated phylogenetic relationships among eastern Pacific temperate anchovies (genus Engraulis) and tropical anchovies (genus Cetengraulis) with neighbour‐joining and Bayesian tree analysis of a 521‐bp segment of mitochondrial DNA cytochrome b. Available sequences for five additional engraulid taxa were included to establish polarity of the tree. Bayesian estimates (BEAST) of time to most recent common ancestor (TMRCA) for the nodes in the phylogeny were calibrated with divergence between Cetengraulis edentulus and Cetengraulis mysticetus precipitated by the rise of the Panama Isthmus 2.8–3.2 Ma. Results Neighbour‐joining and Bayesian trees indicate that South American Engraulis anchoita (Argentina) and Engraulis ringens (Chile) together are basal sister taxa to the California anchovy (Engraulis mordax) and Old World anchovies (Engraulis japonicas, Engraulis australis, Engraulis capensis and Engraulis encrasicolus). The two tropical species of Cetengraulis are sister‐taxa to Californian E. mordax, even though their phenotypes and ecologies differ markedly. A relaxed molecular clock indicates a TMRCA between Californian E. mordax and Cetengraulis at about 4.2 Ma (3.0–6.3 Ma 95% highest probability density). Main conclusions The TMRCA between the California anchovy, E. mordax, and tropical Cetengraulis coincides with the formation of the Gulf of California, which provided opportunities for allopatric isolation during climate oscillations. Mid‐Pliocene warming (3.1–2.9 Ma) may have trapped ancestors of Cetengraulis in the Gulf of California, where they evolved digestive tract morphologies to exploit inshore tropical habitats with low plankton productivities. While populations of several other temperate fishes have become isolated in the Gulf of California, few of these derived species show strong adaptive shifts from temperate sister taxa or range expansions into the tropical provinces of the western Atlantic and eastern Pacific.     

Snail shell coiling (re-)evolution and the evo-devo revolution

During the last two decades evolutionary developmental biology has become a major research programme whose findings put into question some concepts lying at the core of the 'Synthetic Theory'. However, some authors are waiting for a 'revolution' in biology, one in which the existing genetic determinism will give way to a new conceptual understanding of the complexity of living organisms. This 'revolution' should necessarily pass through the elaboration of an appropriate theoretical framework integrating the non-linear dynamics of development as its fundamental basis. This objective implies a drastic shift in the way causality is generally understood as well as a purge of numerous convenient but misleading metaphors such as genetic or developmental programmes. Although most authors do not take these metaphors too literally, some persist in employing such 'instructionist' notions in a more literal perspective, and, in doing so, deny some concepts at the core of evolutionary developmental biology. We critically review two recent studies suggesting that shell coiling has re-evolved in a family of limpets (Calyptraeidae, Gastropoda). We stress that this putative re-evolution of snail shell coiling results only from an arbitrary scoring procedure leading us to consider shell coiling as a binary discrete character. We show that the way in which these authors connect this case study to evolutionary theories stems from the unwarranted premise of a linear mapping of genes onto phenotypes where particulate inheritance of morphological characters seems implicitly assumed. We illustrate how the persisting unclear role of genes in morphogenesis allows the maintenance of the adaptationist programme.