Discussion 1 Notes - SINGLE GENE INHERITANCE Concepts of genetic inheritance are ancient Long before Mendel, people had the notion that, for humans, animals and plants, the offspring resembled the parents. All domestic plants and animals have been genetically selected. Genetic inheritance of traits is the basis for development of animal breeds as well as microorganisms used in the pharmaceutical and food industries. Genetics can be a tool applied to molecular biology biochemistry and essentially any other discipline in biology. Humans have over 20,000 genes encoding proteins that function in metabolism, regulation and cell structure. The roles of most genes are still not well understood. We know that we can affect the characteristics of crop plants, animals and microorganisms by genetic selection. Genetics influences our health and our abilities; the environment can also strongly affect these traits. Genes and the role of genes in inheritance were first described for genes in which mutations caused major effects on the growth, development or appearance of an organism. The first genes described were those for which simple patterns of inheritance of 3:1 or 1:1 could be recognized. Patterns of inheritance can generally only be recognized in studies of large populations, but in some simple organisms where all the products of meiosis can be seen, patterns can be detected in even small sample sizes. Modern genetics began with Gregor Mendel who in the 1860’s described genes and their mode of inheritance. If Darwin had been familiar with this work, it would have helped him explain the transmission of traits needed for his model. The laws of inheritance were independently rediscovered in 1900 by Hugo de Vries, Carl Correns, and Erich von Tschermak. Mendel’s laws are now a standard concept in biology. Fungi make up the most well-studied organisms with haploid genetics. Example: We will consider the yeast Saccharomyces cerevisiae, the baker’s or brewer’s yeast This yeast can live happily as a haploid, it has two sexes that can mate, and it has about 5500 genes – researchers have systematically deleted each of the genes to make a collection of 5500 strains, each missing one specific gene. When haploid yeast cells of opposite mating types (called a and α) mate they make a temporary diploid that can undergo meiosis (we will get to the details of meiosis later). This diploid product of the mating process is different from the two starting parents - It can’t mate (so is neither a nor α) - It can sporulate (this is the meiosis process) - It grows as a somewhat bigger cell - It produces buds at both ends of the cell Once a yeast cell has undergone meiosis, all the 4 products of that meiosis are maintained in a little bag called an ascus. It is possible to separate all the cells in the ascus and grow them up to colonies to monitor how traits segregate. When we look at the mating types of the 4 spore colonies from the meiosis, 2 are a and 2 are α. There is no mixing, averaging, modifying – every little ascus sac gives 4 spores, 2 are a and 2 are α. In haploid genetics as with yeast this 2:2 segregation pattern is called Mendelian segregation. So what do we learn about the behaviour of the mating trait from this experiment? - Although the traits seem to disappear in the diploid prior to meiosis, they reappear unchanged in the new offspring - All the spores get one or the other trait - So it looks like the two sexes represent distinct varieties of a single element – in simple terms we will call the discrete element a gene, and the two variants “alleles” of the gene We have an “a” allele coming from one parent, an “α” allele coming from the other parent, and the offspring get one or the other, and the numbers of a and α offspring are equal (and thus reflect the ratios of the parents). So what happens if we look at more than one trait? Some mutations in adenine biosynthesis in yeast can lead to the accumulation of a coloured pigment, such that ade1 and ade2 mutants form colonies that are red So we can follow the segregation of the ade2 allele (cells form red colonies and need supplemental adenine) from the normal or wild type allele (ADE2+) which gives white colonies that grow fine on medium lacking adenine This description of the two versions of the gene implicated in adenine biosynthesis brings up the point of how to designate alleles. For the mating type it was sort of simple, one was a and the other α, and there was no hierarchy. Ultimately we will call these co-dominant alleles. For adenine biosynthesis there was the normal condition, which I called wild type and wrote ADE2+, and the mutant condition that I wrote ade2. Naming wild type and mutant alleles differs slightly from system to system, and has real rules for each system (worms, flies, yeast, people etc.) Basically the logic is that you give a gene a name based on something about the phenotype associated with the gene, that the “normal” state of the gene is called wild type, and that the “plus” symbol is connected to the wild type. So here we call the gene ade because when the gene is not functioning the cells need supplemental adenine; we call it ade2 because it was the second gene identified that had a role in the synthesis of adenine. The specific convention in yeast is three letters and a number, gene names are in italics, the mutant versions of genes are in small letters and the functioning wild type version is in capital letters. If you have multiple different alleles of the same gene they are written as ade2-1, ade2-2 etc. These conventions work pretty well under most situations, but there are always specific cases that can be complicated to address. Sometimes the wild type allele is designated just by +, rather than writing the whole gene name out. As long as it is clear what gene the + represents, this is fine So now we can look at what happens when we cross a strain that is ade2 (and thus forms red colonies) and is a mating type to a strain that is wild type at the ADE2 locus and thus gives white colonies, and is the α mating type. This would be the simplest pattern – just an extension of the 2:2 segregation that was seen when you were looking at the single mating type locus But things are not so simple, you actually get two other patterns – these patterns occur because of what we term Mendel’s Law of Independent Assortment Independent Assortment means that the cells get the a and α information independently of getting the ade2 and ADE2+ information In the first pattern all 4 spores make colonies like the parents, and there are 2 types - this is called a parental ditype or PD In the second pattern there are only 2 types of spores, so a ditype, but they are not like the parents, so a non-parental ditype or NPD The third pattern has all 4 possible combinations, and is a tetratype or TT tetrad So what have we learned? We have a few simple patterns or rules about genes. As we go through the course we will add complexity to these rules and patterns, but the patterns and rules will still underlie our interpretations 1. Genes are discrete elements This can be very abstract – genes are “things” that effect the characteristics of organisms (seed colour, colony colour, eye colour, seed shape…). They are passed on intact from generation to generation, and the frequency in the next generation reflects the frequency in the previous generation But, it is perfectly OK to say we know a lot more than Mendel about the basis of genes – we know they represent discrete patterns of nucleotide sequences in DNA, and if it is easier to think about them this way, go ahead although historically genes were being studied long before we knew anything about the structure of DNA . 2. Different genes are passed on and function independently. This is a real oversimplification, but it presents a good framework that we can build on. These characteristics are codified into two Mendelian laws: Mendel’s first law of equal transmission (segregation) Mendel’s second law of independent assortment
