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Gene interactions SLIDE 1 Gene interactions Phenotype is produced as a result of the interaction among several genes plus the environment. SLIDE 2 Epistasis – Labrador colors We demonstrate the phenomenon of epistasis with the determination of hair color of Labrador dog breed. The dominant version of gene „B” (allele B) determines black color, while the recessive version (allele b) determines brown. Another gene (E) is responsible for the sedimentation of pigment into the skin. If in an individual at least one copy of E gene is dominant (EE or Ee; E; it is the normal allele), then B gene inheritance follows the normal route (BB and Bb: black; bb: brown). However, if E gene occurs in homozygote recessive form (ee; e is the malfunctioned allele), then the dog will be white independently of E gene genotype. SLIDE 3 Pleiotropy – a gene affects several phenotypes Pleiotropy occurs when a single gene influences multiple phenotypic traits. Consequently, a new mutation in the gene will have an effect on several traits simultaneously. The underlying mechanism is that the gene codes for a product that is, for example, used by various cells, or has a signaling function on various targets, or cause the alteration of gene expression of several other genes through complex multistep interactions. The easiest way to explain the mechanism is to use an example. A classic example of pleiotropy is the human disease phenylketonuria. This disease causes mental retardation, and reduced hair and skin pigmentation. The cause is a mutation in a single gene that codes for an enzyme (phenylalanine hydroxylase) that converts the amino acid phenylalanine to tyrosine, another amino acid. The mutation results in a no or reduced conversion of phenylalanine to tyrosine, and phenylalanine concentrations increase to toxic levels, causing damage at several locations in the body. The term pleiotropy comes from the Greek pleio, meaning "many", and tropo, meaning "changes". SLIDE 4 Gene networks A gene network is a cluster of functionally-linked genes, which participate in the same molecular processes and in the formation of a particular phenotype. The one gene network, one phenotype paradigm means, that, in contrast to the one gene, one phenotype principle, a group of interacting genes contribute to the formation of a particular phenotype. The interaction among genes is dynamic, which means that the amounts of participating gene products are dependent on each other. The relationship among the components is hierarchical, that is certain genes have a more pronounced effect on the other than conversely. The members of ontogenic gene networks operate according to a pre-programmed timetable. The steps of ontogenesis are controlled by transcription factors* exerting stimulating or inhibitory effects on each other. Several gene networks operate in an individual in different time and location. The interactions are more frequent within a gene network, than between gene networks. A given component can be the member of more gene networks. For example, oxitocin plays a role in more physiological process: uterine contraction, blood pressure, parental care, etc. SLIDE 5 Interaction among gene products Genes interact with each other through gene products … 1. at the level of gene expression: transcription factors 2. via protein – protein interaction: transcription factors, subunits phosphorylation, etc. 3. via mediators: messengers (hormones, neurotransmitters, cAMP, etc) SLIDE 6 Messages: - The expression of a gene depends on other genes (epistasis) - A single gene contributes to several phenotypes (pleiotropy) - Genes are organized to gene networks Living organisms are systems based on gene interactions Extra requirements page 1 The effect of environment Sex determination In many species sex is determined by environment, such as the position in Crepidula snakes (see slide), or the actual number of sex partners in fishes, which means that if there are much more females than males, they change sex, and vica versa. Weight, height, studying The effect of training and diet on body structure is self evident. The height of modern man was lower than those of Cro Magnon’s as long as until recently. Today, the increase of height (called acceleration) is observable in a single generation. We do not know the reason for this. Learning is largely independent from our genetic blueprint. Genes or environment? Ontogenesis follows a strict program; it is protected by environmental perturbations, which is indicated by the very high similarity of identical twins. It seems to be contradictory that embryogenesis is controlled by a series of dynamic molecular processes, while the course of ontogenesis is very rigid. The major reason for this is that the underlying mechanisms exhibit self-correcting properties and that they resist to environmental and genetic perturbances (this process is called robustness). Extra requirements page 2