The benevolent disorder of lifeThe benevolent disorder of life

Diversity of organisms between science and societyDiversity of organisms between science and society

-- At variance with other scientific disciplines, students of life sciences are observers and observed and therefore are influenced and influence the spirit of times and the prevalent ideologies.

-- Living systems are “multiverse”, that is they present apparently contradictory features at the same time. The spirit of time and the ideologies “suggest” which side of life should be privileged in the observation, hopefully leading to the development of “universal” concepts and theories.

-- Such a choice implicitly entails the development of specific methodological concepts and tools which in turn influence the collection of data and their interpretation.

-- More than other sciences therefore, Biology changes with time always finding local and not universal rules, liable to be

enriched and modified.

Charles Darwin was a 19° century naturalist and a keen observer of nature. Therefore, for him the “individuals”and the species, the subjects of evolutionary processes, were embedded in a complex and reciprocal relationship with environment which Darwin considered as a network of connected parts. His thought was coherent with the pre-modern holistic spirit of his times and confirmed byhis laws of evolution where the direct effect of the

environment was a primary factor “Those laws, taken in their wider meaning are:--The law of growth through reproduction--heredity, almost implicit in reproduction--variability due to the direct or indirect action of living conditions and use and disuse --a growth rhythm so high that it leads to a fight for existence and consequently to natural selection” Darwin . Origin, 1872

In 1847 a group of scientists, mostly physicists and physiologists, published the “Manifesto of medical Manifesto of medical materialistsmaterialists”” where they stated the substantial equivalence between living and non living systems. The Manifesto opened the way to the official introduction of the reduction of living systems to components as the best method in Biology, thus “updating” life sciences to what had happened in Physics and Chemistry. This choice led to the development of physical and chemical methods and their usage in the study of systems through the analysis of their components. Consequently “Ockham’s razor” was applied also to life and the simplest solutions of biological problems were considered always to be the best fitting. Biology itself was fragmented into sub-disciplines, each of them finding its universal “truth” often conflicting with others . The Darwinian “multiversity” concept was abandoned and discussions were centred on the debate between false antinomies.

FROM METHOD TO THEORY.

Mendel was a physicist and the first implicit follower of the reductionist method. The results obtained, were then used by Hugo de Vries for the development of an anti-darwinian “neutralist” and “saltational” theory. This opened a harsh debate between mendeliansand the followers of Galton on the two antinomies, discreteness vs. continuity, chance vs. necessity. For the first time in life sciences the usage a method based on a theoretical assumption ( equivalence between living and non living systems) led to the development oftheories.

MENDELIAN CONCEPTS: (after Mendel’s death) -- Genes and alleles are independent from each other and are randomly sorted at each generation. -- Characters , as in Mendel’s experiments , are solely determined by genes and alleles without any influence of the environment. It is therefore sufficient to study genes to understand characters, the phenotype being completely determined by the sum of the discreteeffects of totally randomly assorted genes (stochastic determinism)

The discovery of DNA and its crystallized structure following suggestions by Erwin Schrodinger led to the formulation of the “informational metaphor” of the so-colled “central dogma” by Fracis Crick in 1958

Basic concepts of the orthodox version of the Basic concepts of the orthodox version of the ““Modern Modern synthesissynthesis”” ,a putative ,a putative ““compromisecompromise”” between chance and between chance and necessity, discreteness and continuity. The antinomy was necessity, discreteness and continuity. The antinomy was not solved but the two opposite features were admitted as not solved but the two opposite features were admitted as coexisting coexisting --Total correspondence between gene and character

--Additivity and independence of genes and alleles leading to phenotypes solely determined by the sum of allele effects

- The genes as the unit of selection and evolution

-Evolution as a continuous change of relative frequencies of discrete entities ( alleles)

--Three main processes: Mutation (total chance), random drift (total chance), natural selection (total necessity)

C.H.Waddington:Epigenetics and “phenotype paradigma”. Genetic control of “attractor” but not of single life paths.Genes, phenotype, environment interactions.

S.Gould and J.Eldredge:“Punctuated equilibria”.Evolution as a discrete process. Different “individuals”( evolution subjects) at different levels of life organisation ( from cell to Biosphere)

--No living system is completely random (equi-probability of possible configurations of components) nor completely ordered ( only one configuration possible)--The “living state of matter” can be maintained only through adaptive change within organisation rules-- During evolution tools (genes) and complex functional systems have been developed, for variability generation, signal perception, and choice of the part of variability to be used in active response to contexts.--Within the frame of “Four dimensions evolution” (Jablonka and Lamb) different groups of organisms use different strategies based on the differential usage of genetic, epigenetic, behavioural, symbolicvariability.--Bacteria use mainly genetic variation ( evolvability potential), plantsepigenetic ( plasticity potential), animals both but also a higher capacity of choosing and changing the environment, humans baseadaptation on inventions and cultures allowing fast modifications of the environment.--There is evidence for selection for evolvability, plasticity and of the molecular tools which allowed human culture formation. --- Selection is never acting as a filter of passive organisms but Selection is never acting as a filter of passive organisms but allwaysallways deriving from deriving from

more or less virtuous interactions between organisms and environmore or less virtuous interactions between organisms and environment ment

Bacteria have developed a series of tools for the exchange of genetic material and for the increase of genetic variability as a response to stress such as the gene RpoS. This gene , is activated by stress and its product activates “mutator” genes which will increase mutation frequency

Somatic mutations may have a high frequency in plants and animals in specific sequences where they are needed as in the case of the “hot spots” in immuno-globulins, localised in the part coding for the antigen recognition site, thus allowing the production of cells endowed with a large antibody variability.

Particularly in plants but also in animals “mobile elements” are activated by stress trough de-methylation and jump all over the genome producing mutations and re-arrangements of the genome. So defence from stress derives from increases of variability

However, as eukaryotes have long lives, mutations are too slow for adaptation to the many changes in environment by which plants and animals are challenged during life cycles. So they do not have a very high evolvability but on the contrary they rely on epigenetic variability

(plasticity), that is quantitative and qualitative gene regulation

(ambiguity)--Alternative splicing--Alternative promoters--Alternative termination sitesIn all these cases alternative poly-peptides are produced following perception of different signals. In animals the highest ambiguity levels are found in genes used for signal perception and connections among neurons. This is for instance the case of neurexins ( more than 2000 proteins from three genes) and DSCAM ( 38000 proteins from one gene). It has been recently shown that in brains alternative splicing is induced by spykes and leads to the production of different proteins.

Post-translational protein ambiguity comes from conformational changes like in prions and complex formation. Calmodulin for instance

can have around 30 different functions

The main epigenetic processes inducing genetic and epigenetic but heritable variability are:

--Gene amplification ( Ex. Flax)--Horizontal transfer through infection by retroviruses in animals and Agrobacterium in plants --DNA Methylation, ( ex. Rice, paramutation etc. )--Histone, methylation, acetilation,phosphorilation, chromosome re-modelling etc.--De-methylation of transposons and retroposons--Somatic recombination and gene conversion

The human adaptive strategy is based on the The human adaptive strategy is based on the usage of the larger biological information reservoir usage of the larger biological information reservoir ever ever ““inventedinvented””, the brain. , the brain.

--Cortex contains hundred billions neurons

-- This potentially allows the connection with one million billions synapses

-- At birth synapses are quasi-random and will eventually be organised during life -- Synapses are formed and maintained only in the presence of signals

-- Brain organisation changes continuously according to signal olthroughout life

Human genetic variability is much lower than that of other Human genetic variability is much lower than that of other

primates although our numbers are far higherprimates although our numbers are far higher

From Kaessman and Paabo, 2002

There are two reasons for this. A)Humans spread throughout the Globe only 50000 years ago starting from a small population in Africa. B)Genotypes of subpopulations in different environments did not differentiated through natural selection as humans adapted the environments through the differentiation of cultures

Human beings on the other hand Human beings on the other hand ““inventedinvented”” many different cultures many different cultures transmitted throughout generations,always changing , mixing, transmitted throughout generations,always changing , mixing, remodelling. Cultures are the fast developing and very efficienremodelling. Cultures are the fast developing and very efficient tools t tools allowing us to become the only species capable to live everywherallowing us to become the only species capable to live everywhere on e on this Planet. We can say then that our evolution, since a few thothis Planet. We can say then that our evolution, since a few thousands usands of us , all africans, left that Continent to colonize the Earth,of us , all africans, left that Continent to colonize the Earth, never never was primarily genetic as in other animals but cultural, change iwas primarily genetic as in other animals but cultural, change in n cultures being the most fast and efficient adaptation method evecultures being the most fast and efficient adaptation method ever r invented on Earth. invented on Earth.

According to the Summer Institute of Linguistics in 2005 there were still 6912 spoken languages, not counting dialects and the existence of a whole hyerarchical structure of human communities, from families to nations, all with their individuality to be continuosly shared with the others as well as an infinite number of thoughts, certainly our species-specific richness.

Our brain can be distiguished from that of other closely related Primates like the chimpanzee through a series of parameters: -- Encephalization index-- Neuron number (hundred billions while genomes only contain around 20.000 genes) -- Speed and efficiency of communication among them-- Plasticity of neuronal organisation-- Perception and exchange of signals-- Wholly innovative areas like the area of Broca for languages. We differ from our “cousins” only for a small number of genes very rapidly evolving only in our lineage such as those for encephalin and ASPM responsible for encephalization, or neurexins, cadherins, reelininvolved in signal perception and neuron connection,or FoxP and others for language and other signalling related sequences.It should be stressed that at birth synapses are quasi-random and are organised during life following signals coming from the environment and particularly other humans. This is why we have an extraordinary capacity to acquire information from our human community. Therefore brain organisation changes very rapidly in the first years of life but changes occur all through life. Therefore our thoughts and behaviour have nothing to do with our DNA unless some key genes are heavily modified.

Life needs variability but also constraints due to communicationbetween components of networks.

--Life is organised in a hierarchy of networks from cells, to colonies and tissues, organisms, populations, species, ecosystems, the biosphere.All levels are subjects/objects of evolutionary change. ----Network dynamic structures allow very fast and efficient communication between different components leading, through non-additive interactions to the formation of functional novelty.( in life A+B=C). --A major part of constraints to randomness derives from the need of complementary structures/functions between interacting components and, in general, from functional vital rules of the system.The network structure may lead to amplification of a single or few changes expanding their effects to other connected components.-- “Hopeful monsters” may occur this way, an example being our species differing from other Primate by a very small number of fast evolving genes leading to a change in the adaptation strategy. --Selection never is a “choice” among passive variants but derives from “active” interactions potentially changing both the evolutionary unit and the selecting network.

The simplest example of communication is the interaction betweenmolecules. Interactions are always between different partners ad lead to a complex with a new function. So also constraints lead to novelty Promoter sequences and protein factors are reciprocally constrained as the regulation of genes occurs through recognition of DNA local “shapes” by proteins or RNA and complex formation, leading to gene induction and repression, ambiguity choices, repair, induction of

mutations, rearrangements, etc.

Recognition and complex formation between cAMP, CRP protein, lactose operon

Protein network Actors network

LE RETI VIVENTI SONO FORNITE DI VICARIANZA E

RIDONDANZA. RESISTONO BENE AL RUMORE

DIFFUSO, MALE A QUELLO MIRATO AI NODI CON

MAGGIORE NUMERO DI COLLEGAaa

At the metabolic and developmental level networks have many nodes with different numbers of links per node. Nodes more equal than others ( from “animal farm”) have more and stronger links. In this case a structural or regulatory change may lead to a hopeful monster and become the driver of further evolution. As the overall number of tools of life is not very high evolution in eukaryotes is due toregulatory modifications where change in amount may result in gross metabolic and developmental qualitative remodelling

All these data notwithstanding, unfortunately the All these data notwithstanding, unfortunately the mechanistic utopia based on the mechanistic utopia based on the cetralcetral dogma isdogma is not dead not dead and has very dangerous consequences:and has very dangerous consequences:In medicine: -the mechanistic view of human systems leads to a fragmented medicine on fragmented bodies not taking into account the network dynamic structure.-everybody is asking geneticists to find the gene for immortality, good behaviour etc. pharmaceutical industries are patenting often useless molecular markers of specific disease etc.-The relevance of primary prevention and the effects of environment on health are underestimated because of the everlasting belief that genes are the only relevant factor controlling our lives-The supposedly genetic control of behaviour favours discrimination and racism of all kinds

In agriculture the green revolution in the “70s was based on the DNA-centric paradigm ad disregarded the influence of environment and the relevance of biodiversity the basic aim of breeding being to obtain “optimal” plants and animals to be cultivated and bred throughout the whole world irrespective of different environmental, social, economic conditions of the contexts. Plant breeders were taught to choose the characters known to be relevant for production on the basis of extant knowledge, to assemble them designing a theoretically optimal future variety (“Donald’s ideotype” from the name of a breeder) and to proceed with selection obtaining the putatively best possible cultivated variety ( cultivar) to be utilised everywhere in the world. Optimization meant homogenization and destruction of extant “non-optimal” genetic variability. Assemblage was carried out in the belief that all characters were independent meaning by that that the change in one direction of one character would not interfere with the others. Almost no attention was given to the possible negative interactions with the different contexts on the basis of the idea that plants and animals could be grown in all conditions provided that sufficient inputs of chemistry ( fertilisers, pesticides etc.) and energy could be artificially added to the agro-ecosystem.

The green revolution released a vast number of new varieties and breeds and certainly increased global food production but only in the industrialised world, parts of Asia and Latin America. Africa was left behind and globally the number of undernourished people decreased only until 1995 increasing again later. The last estimate is of over one billion undernourished people. The loss of agricultural biodiversity is according to FAO 75%.

The species extinction speed is now thousand times faster than in the earlier five ones. This is the result of the optimization/homogenization of the Planet and its effects like the climate change, overbuilding, deforestation, etc, all caused by the promethean utopia of the continuous growth and mechanization of the world.

Nl gr 1/3Nl gr 2/4

Nl gr 18/20

Nl wild type

Effect of the insertion of a gene for rat gluco-corticoid receptor into the genome of Nicotiana langsdorffii. This is an example of “unintended effects”, the main cause of the failure of genetic engineering in plants due to the fact that changing one component of a network damages it and renders plants non productive