Indeed, the norm of reaction of the inbred line is one way to think of the genotype as an abstracted type. Moreover, there is no need to identify the material basis of the genotypic constituents shared by the inbred line. When inbred lines were crossed then self-pollinated, the traits of individuals raised under uniform conditions could be analyzed statistically by employing—and thereby demonstrating—a model of genotypic constituents as pairs of segregating factors.
In these experiments, phenotypes and genotypes as classes still play a role, with the F2 phenotypes being used to identify whether apparently identical F1 phenotypes are heterozygote or homozygote genotypes.
If the answer is yes, the inbred parent could be classified as a different phenotype from the F1 hybrid. Yet, the experimental control of biological material and conditions that make such a mapping possible also provided the Mendelian researchers of the early twentieth century a means to investigate the genotype-as-material-constituents see section 3.
However, in taking up that direction of research what was left unaddressed was the relevance for understanding heredity in naturally varying populations of phenotype-to-genotype mapping and investigations of the constituents of genotype using Mendelian methods. Johannsen does not address those issues which are returned to in section 5 , but he does point to several other concerns about the concepts, methods, and implications of the genotype conception of heredity.
These follow. The continuous variation common in regular populations did not, for Johannsen, contradict the discontinuity of genotypes:. The well-known displacement… of a population… proceeding from generation to generation in the direction indicated by the selection—is due to the existence a priori of genotypical differences in such populations. Such selection changed the relative proportion of genotypes in the population, not any genotype itself.
There could have been room here for reconciliation with the biometrical view of variation in non-experimental populations, but that avenue was not pursued by Johannsen. Mendelian experiments fostered a particulate view of heredity in the way that two factors influence a given trait. In that sense, the old transmission conception had not been fully banished. If this view was to be made into exact science, some method for analyzing the genotypical constitution or genotype as a whole was needed.
Johannsen did not provide one. Given such independent assortment of traits, it would make sense, contra Johannsen, to talk of a pair of factors or genes for crinkly peas. A new transmission conception of heredity was plausible. To put that in another way, the influence of factors that are identical for all members of a species cannot be studied through Mendelian crosses. The genotype-conception of heredity, by centering on genotypic differences associated with phenotypic differences, shifted attention away from the species-typical aspects of the germ cells and subsequent development.
Mendelian analysis focused on differences over similarity , even though both aspects were included in then prevailing conceptions of heredity Sapp Similarity was part of heredity in the sense that, for the eye color of some flies to differ from the rest of the population, the initial cell or zygote of the fly has to be able to develop into an organism that has eyes with color. For the new genotype-conception of heredity, stability of the genotype across generations was the primary fact.
In putting mechanics to the side, the descriptive side of studies of heredity that Johannsen decried can be seen persisting, to some degree, in his original definitions of phenotype and genotype as classes of organisms. The conservatism expressed in Johannsen about identifying the material basis of genes, as the nature of the germ cells shared by a genotype, was not so evident among the Mendelian researchers who quickly came to adopt the new terms gene, genotype, and phenotype during that decade.
Research in laboratory genetics and agricultural breeding extended Mendelian methods productively, but it also allowed some of the conceptual and methodological problems of Johannsen introduced in section 2 to persist and ramify. Departures from independent assortment of traits allowed the identification of linkage groups, in which variants of two or more traits co-occur, which eventually were shown to correspond to the proximity of their place or locus on distinct chromosomes.
Indeed, Mendelian research helped expose properties of the chromosomes, such as their role in sex determination, and investigate many other biological issues. The particulate view was affirmed by producing heritable alterations in phenotypes after bombarding organisms with high-energy ionizing radiation.
It remained central to experiments involving crosses between lines that, as much as possible, those lines were inbred and identical and homozygous for genes influencing all traits apart from for the traits under study. While the identical homozygous genes might have an influence on the development of any focal trait, differences in that trait could be attributed to differences in the genes that were not identical among the crossed lines.
Indeed, by the s heredity had come to refer to the transmission of and cross-generational patterns in these differences, not to the development of the similarities from which differences depart [Sapp ]. Genotype could be applied to classes of organisms with a specific pair of genes or small set of pairs or to the specific pairs of genes themselves matching the connotation of type as an abstraction away from the full set of observed characteristics.
In Mendelian experiments phenotypes-as-classes demarcated by a small set of traits could be used to identify genotypes-as-classes. Mendelian methods of inference based on a small set of traits and pairs of genes were complicated by phenomena that came to be called epistasis, expressivity, penetrance, and incomplete dominance and, to a lesser extent, by a background level of mutation for any gene being studied.
A range of phenotypes may be shown to correspond to the same genotype— expressivity. A phenotype that is associated with a certain genotype may be observed for only a fraction of individuals in or with that genotype— penetrance.
With respect to expressivity and penetrance, researchers try to link the observed variation to conditions occurring during development, stochastic developmental noise, or differences remaining at loci not under study, and to decide where in the range of the trait, say, melanin pigmentation, to demarcate one phenotype from another. Incomplete dominance means the occurrence of an intermediate phenotype e. Incomplete dominance removed some of the ambiguities in using phenotypes to distinguish genotypes, but the combination of the four phenomena and linkage for multiple loci meant that Mendelian researchers had to distinguish among multiple hypotheses about the genotypes consistent with observed patterns of traits in the offspring of crosses.
Background levels of mutation, including mutations in non-germ cells during the lifetime, ensure that even genotypes-as-classes consisting of clones or of identical or monozygotic twins are not made up of strictly identical members.
Nevertheless, with suitable organisms and for certain traits, and under the inbreeding and control of conditions typical of Mendelian experiments, the painstaking work of inferring genotypes as pairs of genes from phenotypes could bear fruit. Not all aspects of the study of heredity could be made an experimental endeavor through Mendelian methods.
There were many traits for which the continuous variation could not be subdivided into discrete phenotypes, let alone linked to genotypes, especially for traits in agriculture of economic interest such as yield of plant and animal varieties or breeds. By the end of the s Ronald Fisher and Sewall Wright had begun to address the need to reconcile the discreteness of genotypes with continuous variation in many observable traits.
In the mathematical models of a field that came to be known as quantitative genetics , differences between unobserved theoretical genotypes in the sense of pairs of genes at each of a large number of loci contribute to differences in the trait, modulated by degrees of correspondingly theoretical dominance and epistasis. Under the reasonable assumption that more of the genes are shared among relatives than in the population as a whole, data on a given trait as it varies across genealogically defined lines or groups of specified relatedness could be analyzed so as to provide predictions of changes in the average value of the trait in the population under selective breeding.
Of course, the trait values and thus the predictions depended on the conditions in which the organisms developed, but in the laboratory and, to varying degrees, in agricultural breeding, conditions could be replicated.
For the breeder, the focus of the quantitative genetic data analysis on differences in the trait makes practical sense; it is not necessary to know the mechanisms through which the traits developed as organisms reacted to conditions. In other words, the meanings of genotype, phenotype, and their distinction again make sense as an abstraction through practices of control over biological materials and conditions in agricultural and laboratory breeding and the allied use of models and analysis of data.
It should also be noted that, in agricultural breeding, the lines or other genealogically defined groups became called genotypes as well. Genotypes in this sense are classes of individuals related by genealogy from a common ancestor or set of ancestors. The relatedness takes a variety of forms—not only pure inbred or cloned lines, but also offspring of a given pair of parents or a set of ancestors or an open pollinated plant variety in which the genes vary within replicable bounds among the generations of individuals in the class.
The corresponding phenotype is then the range of values of the trait or set of traits as they are observed to vary for the genealogically defined line or group in the given location s or situation s. Quantitative genetics extended to humans does not involve controlled breeding, but does rely on relatedness that differs between, say, monozygotic and dizygotic i. Even though a twin pair is not conventionally referred to as a genotype, human quantitative genetics has followed the same idea for data analysis as used in agricultural breeding.
The mathematical models of quantitative genetics could be readily extended from selective breeding to evolutionary change by having theoretical genotypes from a large number of loci each contribute to parameters for surviving and leaving offspring—so-called selection coefficients.
Data on the variation for a trait in a specific group or population could be analyzed so as to estimate the parameters in the model that would generate the observed changes in the average value of the trait over time. Notice, again the separate theoretical genotypes and their contributions, this time to selection coefficients, remain unobserved; the focus of the data analysis could be on differences in the trait, not the mechanisms of trait development.
The complexity of developmental mechanisms, which involve interactions with the environment, was collapsed in the models into the selection coefficients modulated by parameters for dominance between alleles i.
A parallel development, initiated again by Fisher and Wright, as well as by J. Haldane, involved mathematical models of theoretical genotypes at one or a few loci each contributing to the parameters for surviving and leaving offspring. In this field, which came to be known as Population Genetics, estimation of selection coefficients of genotypes inferred from distinct phenotypes was possible, albeit more readily when the populations were subject to artificial selection in the laboratory than when frequencies or changes over time were observed in the wild which was studied in the new field of ecological genetics.
Just as in quantitative genetics, the focus in population genetics was on difference in traits; complexities of development in its ecological context were typically collapsed into the parameters of the models. Some Mendelian researchers extended the investigation of the material basis for genes to their role in developmental processes.
For example, the eyes of fruit flies, normally red, are sometimes white. Geneticists identified the location on the chromosomes that corresponds to the white-eye mutation Morgan and later investigated the pigment-formation metabolic pathway and the enzymes proteins that modulate biochemical interactions involved as fruit fly eyes develop the normal or mutant color e. Research since World War II that came to be known as molecular genetics or molecular biology went on to identify DNA as the chemical basis of genes and the mechanisms of DNA replication, mutation, transcription to RNA, and translation to polypeptides components of proteins.
Researchers probed the feedback networks that regulate these mechanisms, first in viruses and bacteria, then in complex, multicellular organisms; mapped and modified the specific DNA sequence of organisms; compared sequences among taxonomic groups i. Such research, which now occupies the center of biology, renders it plausible to many researchers and commentators that development of traits will eventually be understood in terms of a composite of the influences on the organism over time of identified DNA variants see entry on gene.
Johannsen, as noted earlier and conveyed in the contrast between the method of figure 2 and the theory of figure 1 , provided no method to divide a natural varying population into phenotypes as classes of organisms, let alone to use these classes to identify genotypes as classes within such populations. What would be required then in order to apply his terms and distinction in the study of heredity for natural varying populations?
A number of pathways can be delineated:. As a sociological, not a logical matter, success in engineering may underwrite theoretical generalizing and both may, in turn, make more plausible any assumed extension to naturally varying populations. Together with further experiments, these pathways may eventually lead to success in re-integration. It could be imagined that the processes exposed in controlled conditions would eventually explain heredity in naturally varying populations.
However, there is no guarantee that the original experimental basis for the genotype-phenotype distinction or subsequent developments must lead to effective engineering, theoretical generalization, or likening that clarifies. This will enable them to compare the roles that different genes play in the development of the fruit fly compared with the honey bee.
Peter and his colleagues have found that D. For example, both species have a gene called caudal. Its role has evolved from turning a gene on to turning a gene off. This is not a unique finding in itself. Although this research is still developing, Peter hopes their work will add significantly to the current understanding of development and evolution. Visit the National Human Genome Research Institute website to learn more about comparative genomics and model organisms. Add to collection.
Nature of science Animal and cell-based models are often needed to explore the complexity of human development and genetics. And at the end, once we do this with all the lectures, let's discuss the overall syllabus - is there a better way to organize all this material for such a fast-paced class. Today, I tackle the important but difficult task of explaining why "gene for" idea is wrong and how to think in a more sophisticated manner about the way genes affect phenotype.
One often hears news reports about discoveries of a "gene for X", e. This is an incorrect way of thinking about genes, as it implies a one-to-one mapping between genes and traits.
This misunderstanding stems from historical precedents. The very first genes were discovered decades ago with quite primitive technology. Thus, the only genes that could be discovered were those with large, dramatic effects on the traits. For instance, a small mutation change in the sequence of nucleotides in the gene that codes for RNA that codes for one of the four elements of the hemoglobin protein results in sickle-cell anemia.
The red blood cells are, as a result, misshapen and the ability of red blood cells to carry sufficient oxygen to the cells is diminished. Due to such dramatic effects of small mutations, it was believed at the time that each gene codes for a particular trait. Most traits are affected by many genes, and most genes are involved in the development of multiple traits.
A genome is all the genetic information of an individual. Each cell in the body contains the complete genome. Genomes i. Exact DNA sequence of an individual is its genotype. The collection of all observable and measurable traits of that individual is phenotype. If every position and every function of every cell in our bodies was genetically determined, we would need trillions of genes to specify all that information.
Yet, we have only about 26, genes. All of our genes are very similar to the equivalent genes of chimpanzees, yet we are obviously very different in anatomy, physiology and behavior from chimpanzees. Furthermore, we share many of the same genes with fish, insects and even plants, yet the differences in phenotypes are enormous. Thus, it follows logically that the metaphor of the genome as a blueprint for building a body is wrong. It is not which genes you have, but how those genes interact with each other during development that makes you different from another individual of the same species, or from a salmon or a cabbage.
But, how do genes interact with each other? Genes code for proteins. Some proteins interact with other proteins. A single allele causes the delayed flowering. Thus, the multiple alleles at the Lf locus represent an allelic series, with each allele being dominant over the next allele in the series. Mendel's early work with pea plants provided the foundational knowledge for genetics, but Mendel's simple example of two alleles, one dominant and one recessive, for a given gene is a rarity.
In fact, dominance and recessiveness are not actually allelic properties. Rather, they are effects that can only be measured in relation to the effects of other alleles at the same locus.
Furthermore, dominance may change according to the level of organization of the phenotype. Variations of dominance highlight the complexity of understanding genetic influences on phenotypes. Murfet, I. Flowering in Pisum : Multiple alleles at the Lf locus. Heredity 35 , 85—98 Parsons, P. The evolution of overdominance: Natural selection and heterozygote advantage.
Nature , 7—12 link to article. Stratton, F. The human blood groups. Nature , link to article. Chromosome Theory and the Castle and Morgan Debate.
Discovery and Types of Genetic Linkage. Genetics and Statistical Analysis. Thomas Hunt Morgan and Sex Linkage. Developing the Chromosome Theory.
Genetic Recombination. Gregor Mendel and the Principles of Inheritance. Mitosis, Meiosis, and Inheritance. Multifactorial Inheritance and Genetic Disease. Non-nuclear Genes and Their Inheritance.
Polygenic Inheritance and Gene Mapping. Sex Chromosomes and Sex Determination. Sex Determination in Honeybees. Test Crosses. Biological Complexity and Integrative Levels of Organization.
Genetics of Dog Breeding. Human Evolutionary Tree. Mendelian Ratios and Lethal Genes. Environmental Influences on Gene Expression. Epistasis: Gene Interaction and Phenotype Effects.
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