Classical and Molecular Genetics

Synthetic biology (SynBio) covers two main areas: application engineering, exemplified by metabolic engi- neering, and the design of life from artificial building blocks. As the general public is often reluctant to embrace synthetic approaches, preferring nature to artifice, its immediate future will depend very much on the public’s reaction to the unmet needs created by the pervasive demands of sustainability. On the other hand, this reluctance should not have a negative impact on research that will now take into account the (...) existence of the multiple transitions that cells face over time. The ages of life—birth, development, maturation, senescence and death—reflect specific key transitions and have, until now, rarely been taken into account in SynBio designs. This results in a mismatch between novelty and the very long evolutionary time that led to the existing chassis [remember that this is the common term used to describe the cellular framework as seen by synthetic biologists (de Lorenzo & Danchin, 2008)]. It also implies that, in general, transitions between growth stages will be taken into account with the appro- priate embodiment of highly specific processes. This is particularly important when adapting new models to their host, whether natural or artificial. Adaptation fol- lows two stages, short-term accommodation of new entities and long-term assimilation into the cell as a whole. This requires discrimination between classes of entities. We suggest that proteins playing the essential role of Maxwell’ demons, here named Maxwell’s dis- criminators (MxDs) to refer to their original function, will permit the assimilation and accommodation of artificial constructs. As a consequence, we can foresee that class discrimination, beyond mere recognition, will be implemented in SynBio 2.0, leading to an authentic par- adigm shift (Kuhn, 1996), based on conceptions that embody information as a genuine currency of reality. (shrink)

One claim found in the received historiography of the biometrical school (comprised primarily of Francis Galton, Karl Pearson, and W. F. R. Weldon) is that one of the biometricians' great flaws was their inability to look past their population-focused, statistical, gradualist understanding of evolutionary change – which led, in part, to their ignoring developments in cellular biology around 1900. I will argue, on the contrary, that the work of the biometricians was, from its earliest days, fundamentally concerned with connections between (...) statistical patterns of inheritance and the underlying cellular features that gave rise to them. Such work remained current with contemporary knowledge of chromosomes, cytology, and development; in this article, I explore the first case. The biometricians were thus well positioned to understand the relationship between the patterns of Mendelian inheritance and the statistical distributions with which they primarily occupied themselves. Ignorance of this connection, then, is not the reason why they rejected Mendelism. Further, both Galton and Weldon – though each in their own unique way – decided to turn to biological detail as a way to better justify the generality of their statistical approaches to heredity. Perhaps paradoxically, then, for these biometricians, detail offered an approach to theoretical generality. (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 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)

ITA: In questo articolo analizzerò la differenza tra il concetto di ereditarietà e quello di ereditabilità. In primo luogo, evidenzierò come i due concetti derivino storicamente da differenti tradizioni nello studio della variabilità fenotipica e del rapporto genotipo-fenotipo. Secondariamente, illustrerò gli aspetti teorici e metodologici alla base dei due concetti, che sono peraltro collegati a differenti aree delle scienze biologiche. Infine, spiegherò brevemente come si sia recentemente tentato, con molte difficoltà, di connettere lo studio dei meccanismi dell’ereditarietà allo studio dell’ereditabilità. (...) Nel discutere le questioni di cui sopra, farò riferimento a tratti psicologici come l’intelligenza dal momento che è proprio dallo studio di questo tipo di tratti che sono emersi i maggiori problemi teorici e metodologici, nonché le controversie più intense. -/- ENG: In this paper, I analyse the distinction between heredity and heritability. First, I highlight that the two concepts derive from different historical traditions in the study of phenotypic variability and of the genotype-phenotype relationship. Second, I illustrate the theoretical and methodological aspects connected to the two concepts, which are traditionally associated with different areas of biological research. Then, I focus on recent attempts aimed at connecting with each other the analysis of heredity and of heritability. In my discussion, I shall often refer to human psychological traits such as intelligence. Indeed, most theoretical and methodological discussions have emerged with respect to the study of these traits. (shrink)

Somatic diversification of antigen receptor genes depends on the activity of enzymes whose homologs participate in a mutagenic DNA repair in unicellular species. Indeed, by engaging error-prone polymerases, gap filling molecules and altered mismatch repair pathways, lymphocytes utilize conserved components of genomic stress response systems, which can already be found in bacteria and archaea. These ancient systems of mutagenesis and repair act to increase phenotypic diversity of microbial cell populations and operate to enhance their ability to produce fit variants during (...) stress. Coopted by lymphocytes, the ancient mutagenic processing systems retained their diversification functions instilling the adaptive immune cells with enhanced evolvability and defensive capacity to resist infection and damage. As reviewed here, the ubiquity and conserved character of specialized variation-generating mechanisms from bacteria to lymphocytes highlight the importance of these mechanisms for evolution of life in general. (shrink)

Weak inflammatory response after Salmonella infection can cause persistent infection and facilitate the long survival of pathogens. Honey can induce key immunomodulators such as TNF-α, interleukin-6 (IL-6) and IL-1, that it can be used in the treatment of bacterial infectious diseases caused by Salmonella typhi. The purpose of this study is to determine the effect of honey on the mRNA expression of IL-6 in Salmonella enterica Typhi induced of BABL/c mice. The study used experimental pretest-posttest control design. Honey treatment was (...) given for 7 days commencing after the induction of Salmonella bacteria. 20 BABL/c males mice whose weight 25-29 grams, were divided into four groups where 5 mice per group within; the negative control group was given regular feed without bacteria induction, the positive control group was given regular feed with bacteria induction, 0.27 ml/kg-weight honey group and 0.27 ml/kg-weight of Propolis honey group. Blood samples for examination of mRNA expression was examined three times that prior to the induction, 24 hours after induction and 72 hours after induction of Salmonella. The results showed that 0.27 ml/kg-weight of Propolis honey group showed the highest mRNA expression (p = 0.000) for both after 24 hours after induction of Salmonella typhi (p = 0.000) and 72 hours after induction of Salmonella typhi (p = 0.000). We conclude that there was effect of honey on the mRNA IL-6 expression in Salmonella typhi induced of BALB/c mice. (shrink)

Gregor Mendel (1822-1884) was the first to explain that certain 'traits' were inherited in plants from one generation to the next. These would later become known as genes. Frederich Miescher in 1869 analyzed a substance from the nucleus of cells, which he therefore called nuclein. Further study of nuclein revealed that it contained elements like hydrogen, oxygen, nitrogen and phosphorous, with a specific ratio of nitrogen to phosphorous. Then in 1878 Albrecht Kossel determined that nuclein contained nucleic acid, from which (...) he isolated five nucleobases (nitrogen compounds now referred to by the letters C, G, A, T, U representing cytosine, guanine, adenine, thymine, and uracil). It was also discovered that ribose, a sugar was present in the nuclein compound. What Miescher had isolated from the cell nucleus was actually what would latter be identified as DNA (Deoxyribonucleic acid). C. H. Waddington (1905 - 1975) first proposed the term “epigenetics” in 1942 to describe the region between the gene and the whole organism (phenotype) [3]. Today, what is called the epigenome refers to all the chromosomal modifications, DNA modifications, chromatin protein modifications and their complexes. It is the epigenome that determines both the expression of the genes and their inheritance. R. A. Jorgenson reports [4], "Many of these modifications appear to be “programmable” and to be “read out” to influence chromosomal functions." Nobel laureate Barbara McClintock stated this revolutionary proposal more clearly in her Nobel lecture [5], “to determine the extent of knowledge the cell has of itself, and how it utilizes this knowledge in a ‘thoughtful’ manner when challenged.” In 1960 R. A. Brinks suggested that chromosomes possess a paragenetic function in addition to their genetic function [7]. The physical nature of the paragenetic function is characterized by the variety of forms or states of chromatin that can reside at any genetic locus. While the genetic function is stable, the paragenetic function is labile and programmable in ontogeny. It is this latter function that allows organisms to transfer informational macromolecules (RNA and proteins) in a systematic and regulated manner over what is known as the “RNA information superhighway.” Given this capacity, organisms may be able to store information at numerous genetic loci in the form of paragenetic chromatin states, which can be reprogrammed during ontogeny or environmental stress [8]. This reprogrammable system could operate over the whole organism as a storage device, allowing it to make informed ‘decisions' during growth and development, or in response to the environment. Such processing capacity could be considered a form of ‘intelligence,' which also could be passed on to future generations. The study of the flow of information within and between cells and organisms represents the cutting edge of modern biological research. While physical correlates of cognitive behavior in living organisms are being discovered, it does not spell reduction to such correlates. The electronic activity within the physical components of a radio, for example, may be minutely determined, but ultimately it is not merely the electrical activity that produces the intelligent speech that is heard. Only the intelligent person whose voice is being broadcast through the radio can explain that. Without the broadcaster, the radio would sit silently even though fully functional. An organism without its living agency also appears to be devoid of metabolic activity although all the chemical components are fully present. How to connect life to matter will be the ultimate challenge that has to be met. This will prove to be a philosophical problem we hope to address in the near future. (shrink)

This research was carried out in order to verify by simulation Mendel’s laws and seek for the clarification, from the author’s point of view, the Mendel-Fisher controversy. It was demonstrated from: the experimental procedure and the first two steps of the Hardy-Weinberg law, that the null hypothesis in such experiments is absolutely and undeniably true. Consequently, repeating hybridizing experiments as those showed by Mendel, it makes sense to expect a highly coincidence between the observed and the expected cell frequencies. By (...) simulation, 30 random samples were generated with size equal to the number of observations reported by Mendel for his single trait trial, in this case, seed shape; assuming complete dominance, with genes A and a; likewise, it was simulated the results for the experiment with two traits, segregating in separate chromosomes, in this case seed shape, as before, and albumen color, with genes B and b, both loci with complete dominance. In the case of a single trait, the data only showed evidence for rejecting the null hypothesis (Ho ) in 1/30 samples, with (P<0.05). In the case of the 30 samples of the two traits experiment, (Ho ) was rejected only on 3/30 times, when it was set a = 0.05. In both simulations there was a high correspondence between the observed and expected cell frequencies, which is simply due to the fact that (Ho ) is true, and under these conditions, that is what would to expect. It was concluded, that Mendel had no reason to manipulate his data in order to make them to coincide with his beliefs. Therefore, in experiment with a single trait, and in experiments with two traits assuming complete dominance, segregation ratios are 3:1; and 9:3:3:1, respectively. Consequently, Mendel’s laws, under the conditions as were described are absolutely valid and universal. (shrink)

Personalized genomics companies (PG; also called ‘direct-to-consumer genetics’) are businesses marketing genetic testing to consumers over the Internet. While much has been written about these new businesses, little attention has been given to their roles in science communication. This paper provides an analysis of the gene concept presented to customers and the relation between the information given and the science behind PG. Two quite different gene concepts are present in company rhetoric, but only one features in the science. To explain (...) this, we must appreciate the delicate tension between PG, academic science, public expectation, and market forces. (shrink)