Genotypes and Phenotypes

Recent trends in psychiatry involve a transition from categorical to dimensional frameworks, in which the boundary between health and pathology is understood as a difference in degree rather than as a difference in kind. A major tenet of dimensional approaches is that no qualitative distinction can be made between health and pathology. As a consequence, these approaches tend to characterize such a threshold as pragmatic or conventional in nature. However, dimensional approaches to psychopathology raise several epistemological and ontological issues. First, (...) we review major sources of evidence usually recruited in support of the dimensional trend (focusing on clinical observation and biological data), and we show that these are connected to different conceptualizations of how dimensional traits extend across health and pathology. Second, we criticize two unquestioned assumptions that stand at the core of the dimensional trend: a) that there is continuity from health to pathology at the symptomatic level; b) that such continuity reflects an underlying continuity in the genetic liability for pathological conditions. Third, we argue against the idea of a conventional threshold by showing that such a view implies a linear relationship between the genotype and the phenotype. Fourth, drawing on epigenetics and developmental biology, we offer a characterization of mental disorders as stable and dynamic constellations of multi-level variables that differ qualitatively from ‘healthy states’. We conclude by showing that our account has several theoretical advantages over both categorical and dimensional approaches. Notably, it provides crucial insights into psychological development over time and individual differences, with major implications in terms of intervention and clinical decision-making. (shrink)

Under the assumption that anticipatory models are required for anticipatory behavior, an important question arises about the different manners in which organisms acquire anticipatory models. This article aims to articulate four different non-exhaustive ways that anticipatory models might possibly be acquired over both phylogenetic and ontogenetic timescales and explore the relationships among them. To articulate these different model-acquisition mechanisms, four schematics will be introduced, each of which represents a particular acquisition structure that can be used for the purposes of comparison, (...) analysis, and hypothesis formulation. By bringing to the fore the differences and similarities between each of the four ways that anticipatory models are acquired, a more complete picture of both anticipatory behavior and its pervasive role in biological self-maintenance can be offered. In doing so, this article helps not only to shed light on how anticipatory behavior might arise in the wide range of organisms that it has been observed in but also to throw into relief the subtle and often still overlooked causal interplay between ontogenetic and phylogenetic plasticity. (shrink)

ENG: We all have our own ideas about what it is like to be intelligent. Indeed, even the experts disagree on this topic. This has generated diverse theories on the nature of intelligence and its genetic and environmental bases. Many scientific and philosophical questions thus remain unaddressed: is it possible to characterize intelligence in scientific terms? What do IQ tests measure? How is intelligence influenced by genetics, epigenetics, and the environment? What are the ethical and social implications of the research (...) on this topic? This book aims to provide the readers with the conceptual resources to critically analyze scientific findings and orientate themselves in this multi-faceted debate across biology, psychology, neuroscience, philosophy, and anthropology. -/- ITA: Ognuno di noi ha una propria idea di cosa significhi essere intelligenti, tanto che anche gli scienziati esperti in materia hanno opinioni differenti al riguardo. Ciò ha contribuito a generare teorie contrastanti sulla natura dell’intelligenza e su quali siano le sue basi genetiche e ambientali. Non è un caso, dunque, che diverse domande scientifiche e filosofiche restino ancora aperte: è possibile caratterizzare scientificamente l’intelligenza? Cosa misurano i test del QI? In che modo genetica, epigenetica e ambiente influenzano l’intelligenza? Quali sono le implicazioni etiche e sociali della ricerca sull’argomento? Oltre ad analizzare questi problemi, il testo intende fornire gli strumenti concettuali necessari per leggere criticamente i dati scientifici e orientarsi in uno sfaccettato e affascinante dibattito a cavallo tra biologia, psicologia, neuroscienze, filosofia e antropologia. (shrink)

Causation has multiple distinct meanings in genetics. One reason for this is meaning slippage between two concepts of the gene: Mendelian and molecular. Another reason is that a variety of genetic methods address different kinds of causal relationships. Some genetic studies address causes of traits in individuals, which can only be assessed when single genes follow predictable inheritance patterns that reliably cause a trait. A second sense concerns the causes of trait differences within a population. Whereas some single genes can (...) be said to cause population-level differences, most often these claims concern the effects of many genes. Polygenic traits can be understood using heritability estimates, which estimate the relative influences of genetic and environmental differences to trait differences within a population. Attempts to understand the molecular mechanisms underlying polygenic traits have been developed, although causal inference based on these results remains controversial. Genetic variation has also recently been leveraged as a randomizing factor to identify environmental causes of trait differences. This technique—Mendelian randomization—offers some solutions to traditional epidemiological challenges, although it is limited to the study of environments with known genetic influences. (shrink)

This essay explores the relation between nature and culture and analyses it from the perspective of contemporary evolutionary theory. Both animals and humans are conceived of as attaining both natural and cultural features that interact with each other on a number of levels of varying complexity: nature as cultural, nature as influenced by culture, culture as natural, and culture as influenced by nature. “Nature as cultural” is meant to express a decoupling of behavioral/phenotypic changes of an organism from its genetic (...) determination. “Nature as influenced by culture” is the idea of niche construction, wherein such decoupled changes can causally feedback to genetic reality, thereby influencing the evolutionary features of downstream species. “Culture as natural” portrays how cultural structures of humans and animals persist through the generations, accumulate incurred changes, and evolve in analogous ways to biological natural selection. “Culture as influenced by nature” is the notion that the cultural/linguistic capacities of animals and humans have evolutionarily emerged from precultural history. All this is meant to evaluate the viability of constructing a nature/culture divide. The conclusion is made that the divide seems arbitrary within and between human and animal life when considering how the differences between the natural and cultural dynamics of humans and animals are modelled as differences of degree, not kind. A potential approach in using the concept of consciousness to recontextualize a nature/culture divide in terms of the possession of consciousness is proposed at the end. (shrink)

This paper challenges the common assumption that some phenotypic traits are quantitative while others are qualitative. The distinction between these two kinds of traits is widely influential in biological and biomedical research as well as in scientific education and communication. This is probably due to both historical and epistemological reasons. However, the quantitative/qualitative distinction involves a variety of simplifications on the genetic causes of phenotypic variability and on the development of complex traits. Here, I examine three cases from the life (...) sciences that show inconsistencies in the distinction: Mendelian traits, Mendelian diseases, and polygenic mental disorders. I show that these traits can be framed both quantitatively and qualitatively depending, for instance, on the methods through which they are investigated and on specific epistemic purposes. This suggests that the received view of quantitative and qualitative traits has a limited heuristic power—limited to some local contexts or to the specific methodologies adopted. Throughout the paper, I provide directions for framing phenotypes beyond the quantitative/qualitative distinction. I conclude by pointing at the necessity of developing a principled characterisation of what phenotypic traits, in general, are. (shrink)

这是一个对行为上基因/环境相互作用的极好的回顾,尽管有点过时,但却是一个简单而值得阅读的。他们从双胞胎研究开始,这些研究显示了遗传学对行为的压倒性影响。他们注意到朱迪思·哈里斯越来越广为人知的研究,这 些研究扩展并总结了共享家庭环境对行为几乎没有影响的事实,领养的孩子长大后与选择的继兄弟姐妹一样不同。随机。一个基本点,他们(和几乎所有谁讨论行为遗传学)没有注意到的是,数百(取决于你的观点)人类行为普 遍性,包括我们个性的所有基本,是由我们的基因100%决定,与法线没有变化。每个人都把树看成一棵树,而不是一块石头,寻找和吃食物,生气和嫉妒等等。因此,他们主要讨论的是,环境(文化)能在多大程度上影响各 种特征的显示程度,而不是它们的外观。 最后,他们以通常的政治正确方式讨论优生学,没有注意到我们和所有生物体是自然优生学的产物,并且试图用医学、农业和整个文明来击败自然选择,灾难性的任何社会,坚持这样做。多达50%的所有受孕,或大约1亿/年 ,以早期自然流产结束,几乎所有的母亲都没有意识到。这种对缺陷基因的自然剔除推动了进化,使我们相对地保持遗传健康,并使社会成为可能。基因足以破坏文明,但人口过剩会先破坏文明。 那些希望从现代两个系统的观点来看为人类行为建立一个全面的最新框架的人,可以查阅我的书《路德维希的哲学、心理学、Min d和语言的逻辑结构》维特根斯坦和约翰·西尔的二等奖(2019年)。那些对我更多的作品感兴趣的人可能会看到《会说话的猴子——一个末日星球上的哲学、心理学、科学、宗教和政治——文章和评论2006-2017 年'3rd ed(2019)。.

Noting minimal philosophical attention to the shift of the meanings of “genotype” and “phenotype,” and their distinction, as well as to the variety of meanings that have co-existed over the last hundred years, this note invites readers to join in exploring the implications of shifts that have been left unexamined.

According to the proponents of Developmental Systems Theory and the Causal Parity Thesis, the privileging of the genome as “first among equals” with respect to the development of phenotypic traits is more a reflection of our own heuristic prejudice than of ontology - the underlying causal structures responsible for that specified development no more single out the genome as primary than they do other broadly “environmental” factors. Parting with the methodology of the popular responses to the Thesis, this paper offers (...) a novel criterion for ‘causal primacy’, one that is grounded in the ontology of the unique causal role of dispositional properties. This paper argues that, if the genome is conceptualised as realising dispositional properties that are “directed toward” phenotypic traits, the parity of ‘causal roles’ between genetic and extra-genetic factors is no longer apparent, and further, that the causal primacy of the genome is both plausible and defensible. (shrink)

Mehlman and Li offer a framework for approaching the bioethical issues raised by the military use of genomics that is compellingly grounded in both the contemporary civilian and military ethics of medical research, arguing that military commanders must be bound by the two principles of paternal- ism and proportionality. I agree fully. But I argue here that this is a much higher bar than we may fully realize. Just as the principle of proportionality relies upon a thorough assessment of harms (...) caused and military advantage gained, the use of genomic research, on Mehlman and Li’s view, will require an accurate understanding of the connection between genotypes and phenotypes – accurate enough to ameliorate the risk undertaken by our armed forces in being subject to such research. Recent conceptual work in evolutionary theory and the philosophy of biology, however, renders it doubtful that such knowledge is forthcoming. The complexity of the relationship between genotypic factors and realized traits (the so-called ‘G→P map’) makes the estimation of potential military advantage, as well as potential harm to our troops, incredibly challenging. Such fundamental conceptual challenges call into question our ability to ever satisfactorily satisfy the demands of a sufficiently rigorous ethical standard. (shrink)

In the contemporary biomedical literature, every disease is considered genetic. This extension of the concept of genetic disease is usually interpreted either in a trivial or genocentrist sense, but it is never taken seriously as the expression of a genetic theory of disease. However, a group of French researchers defend the idea of a genetic theory of infectious diseases. By identifying four common genetic mechanisms (Mendelian predisposition to multiple infections, Mendelian predisposition to one infection, and major gene and polygenic predispositions), (...) they attempt to unify infectious diseases from a genetic point of view. In this article, I analyze this explicit example of a genetic theory, which relies on mechanisms and is applied only to a specific category of diseases, what we call “a regional genetic theory.” I have three aims: to prove that a genetic theory of disease can be devoid of genocentrism, to consider the possibility of a genetic theory applied to every disease, and to introduce two hypotheses about the form that such a genetic theory could take by distinguishing between a genetic theory of diseases and a genetic theory of Disease. Finally, I suggest that network medicine could be an interesting framework for a genetic theory of Disease. (shrink)

Genes are thought to have evolved from long-lived and multiply-interactive molecules in the early stages of the origins of life. However, at that stage there were no replicators, and the distinction between interactors and replicators did not yet apply. Nevertheless, the process of evolution that proceeded from initial autocatalytic hypercycles to full organisms was a Darwinian process of selection of favourable variants. We distinguish therefore between Neo-Darwinian evolution and the related Weismannian and Central Dogma divisions, on the one hand, and (...) the more generic category of Darwinian evolution on the other. We argue that Hull’s and Dawkins’ replicator/interactor distinction of entities is a sufficient, but not necessary, condition for Darwinian evolution to take place. We conceive the origin of genes as a separation between different types of molecules in a thermodynamic state space, and employ a notion of reproducers. (shrink)

In a now classic paper published in 1991, Alberch introduced the concept of genotype–phenotype (G!P) mapping to provide a framework for a more sophisticated discussion of the integration between genetics and developmental biology that was then available. The advent of evo-devo first and of the genomic era later would seem to have superseded talk of transitions in phenotypic space and the like, central to Alberch’s approach. On the contrary, this paper shows that recent empirical and theoretical advances have only sharpened (...) the need for a different conceptual treat- ment of how phenotypes are produced. Old-fashioned metaphors like genetic blueprint and genetic programme are not only woefully inadequate but positively misleading about the nature of G!P, and are being replaced by an algorithmic approach emerging from the study of a variety of actual G!P maps. These include RNA folding, protein function and the study of evolvable soft- ware. Some generalities are emerging from these disparate fields of analysis, and I suggest that the concept of ‘developmental encoding’ (as opposed to the classical one of genetic encoding) provides a promising computational–theoretical underpinning to coherently integrate ideas on evolvability, modularity and robustness and foster a fruitful framing of the G!P mapping problem. (shrink)

To construct a synthetic cell we need to understand the rules that permit life. A central idea in modern biology is that in addition to the four entities making reality, matter, energy, space and time, a fifth one, information, plays a central role. As a consequence of this central importance of the management of information, the bacterial cell is organised as a Turing machine, where the machine, with its compartments defining an inside and an outside and its metabolism, reads and (...) expresses the genetic program carried by the genome. This highly abstract organisation is implemented using concrete objects and dynamics, and this is at the cost of repeated incompatibilities (frustration), which need to be sorted out by appropriate «patches». After describing the organisation of the genome into the paleome (sustaining and propagating life) and the cenome (permitting life in context), we describe some chemical hurdles that the cell as to cope with, ending with the specific case of the methionine salvage pathway. (shrink)