I would now like to expand on this idea that a patient is a point on a reaction Norm by taking apart the concept of reaction norms and showing you a bit of what difference they make to our analysis to begin with Evolution involves a regular alternation between genotypes that contain information and phenotypes that consist of matter this is an important distinction between information and matter because different sorts of things go on in each of them a motto from Le vanveen is that evolution is the control of development by ecology and I think as I step through this you'll see what vanveen meant this picture which was originally sketched by dick Lenton shows a regular alternation between genotype space and phenotype space so you should think of this as being uh the Universe in which DNA sequences exist and this is being the universe in which organisms exist down here naturally they are connected to each other and they contain each other in some ways the First Transformation here from G1 to P1 from genotype to phenotype is development that's transformation one and it's at this point that genes interact with environments to map the information in genotypes into the material in phenotypes that's where reaction Norms come in T2 is ecology and behavior that's what determines who survives and reproduces T3 is mating reproduction and sum of genetics that determines the array of gametes that's going to form the Next Generation and then T4 is genetics and reproduction that determines how the array of haid gametes is transcribed into a set of diploid zygotes this is going on in every generation so evolution is operating both in genotype space and in phenotype space and selection is acting on phenotypes development is determining the expression of phenotypes development is intimately built in to the apparatus of microevolution at this stage now the result of that kind of Developmental transformation is a reaction Norm so here is one possible reaction Norm here you see temperature an environmental variable on the x-axis the value of a trait size of maturity on the Y AIS and a line relating the two things so you can say that a reaction Norm expresses the phenotype as a function of the environment here you see a depiction of a population it consists of a bundle of reaction Norms each one of these reaction Norms belongs to a particular genotype and the population consists of a set of genetically heterogeneous individuals each one of which had the potential to produce this value of the trait depending on the temperature at which it was raised and we can calculate a mean reaction Norm for the whole population however the concept reaction Norm originally is bound to the concept of genotype a genotype has a reaction Norm now traits can have markedly different kinds of of expression in one of the earlier lectures we pointed out that traits have very different evolutionary ages they also have very different phenotypic plasticities some of them are very insensitive to environmental change so for example in organisms like us the number of digits the number of fingers or toes is very insensitive to the kind of nutrition we have we all always end up with five here the genotypes have just been separated by different colors just to show you that different genotypes are always producing five fingers or toes no matter what nutritional environment they're in other traits for example fecundity are sensitive to changes in the environment so G1 in this case is quite sensitive to changes in nutrition when it's well fed fed it has many offspring when it's poorly fed it has few G3 is less sensitive it has a flatter reaction Norm so that also gets across another concept and that is that the slope of the reaction Norm is a measure of the sensitivity of that trait to changes in the environment because of this differential sensitivity genetic correlations can actually change sign depending on the environment and when there's a a change in the sign of genetic correlation or covariance across environments then a developmental mechanism is strongly modulating the expression of genetic variance and covariant that means that the response to selection is dependent not only on the standing genetic variance and covariance but it's also dependent upon the way in which it is expressed and that can change with environment now genetic correlations can produce indirect selection that has surprising effects in some environments selection for an increase in one trait might cause a correlated increase in another trait in other environments selection for an increase in one trait may cause a correlated decrease in the other trait the environments intermediate to those described selection on one trait won't be correlated with any response in the other at all so reaction Norms are important modulators of selection r responses and that becomes especially important when we're trying to evaluate the effects of tradeoffs here for example is a detailed experiment that was done on dropa mercatorum by Martin gabart he studied aged eclosion and weighted eclosion and he raised basically sets of families derived from two females now the nice thing about these females of drop mercatorum is that if you don't give them males to mate with they will still produce viable Offspring and they will do it asexually so each of the small envelopes down here consists of a group of identical siblings from one mother and this is from the other mother so you have six groups of identical siblings from one mother and six groups of identical siblings from another mother raised out across different yeast concentrations which allows for a precise measurement of reaction Norms Martin observed a positive genetic correlation when the Flies were well fed and growing rapidly that's this 1.5% yeast concentration here and you can see that the slope of this line is steep and positive and he observed a negative genetic correlation when they were poorly fed and growing slowly and the slope of this line is negative so so this is a shift in genetic correlation between two traits driven by variation in the nutritional environment and that is an experimental confirmation of the idea that reaction Norms are modulating the expression of genetic not only of genetic variation but of genetic co-variation in the phenotype now what are the consequences of plasticity for genetic definitions of tradeoffs well genetic correlations among traits can change from population to population within populations over time as Gene frequencies change during the course of development and from environment to environment the responses to selection that are then important for life history can also change in all the same ways this is not just about fruit flies living on yeast in test tubes in the laboratory this is also about things like the demographic transition and the Industrial Revolution which has changed the whole landscape of selection operating on contemporary human beings there are important consequen of plasticity for the human response to selection to these recent important changes in our environments I love this picture because it is such a dramatic and easily understandable depiction of what a difference human uh developmental plasticity makes to human so Otto and aval spits are identical twins they have the the same genomes at the age of 18 Oto began to run distance and aval began to lift weights and four years later at the age of 22 this is what they look like this is how large a difference can result in the human phenotype due to simple differences in lifestyle culture and environment that have nothing to do with genotype now what is the medical significance of phenotypic plasticity one of the areas in which that significance is particularly striking is the developmental origins of health and disease this has been a rapidly growing area which now has its own acronym doad that indicates that things that happen early in life have important consequences later in life thin infants are at increased risk of cardiovascular disease diabetes and obesity in late life we have learned that exposure to starvation conditions either in utero or very early after birth will increase risk of these diseases 50 or 60 years later infants that are born by C-section are at increased risk of atopis and obesity children who have antibiotic treatments before age two are at greater risk of obesity and allergies these are effects mediated by microbiota so these are all reaction Norms these are responses of genotypes to variation in the environment phenotypic plasticity can be of several types it can be reversible so body M weight and muscle mass are reversible Auto and aval spits probably could have reversed the way they appear by switching uh regimes it can be irreversible body height does not change after maturation in humans very much it can be confined to specific developmental stages so for example the whole doad Paradigm tells us that things that happen early in life in particular probably in uh in utero and in childhood are critical and can have KnockOn consequences throughout life some of them can be produced at any stage so tanning and acclamation to altitude can be produced at any stage of development some of them are continuous like maturation and others are discontinuous so for example you can have morphs and water fleas casts and insects where they're morphologically quite distinct things that are being produced by the same genotype and in summary the expression and development of many traits are sensitive to the environment the concept of a reaction Norm is useful when analizing how genes and environments interact to produce phenotypes reaction Norms are properties of genotypes and in humans they are most clearly visualized as the differences that develop between identical twins reared in different environments or undergoing different exercise regimes many medical conditions in adults are sensitive to environments encountered early in life that's the doad paradigm