Mendelian genetics At the beginning of the last section, we mentioned that while you may resemble your parents, you're not an exact copy. Knowing what we do about mitosis and meiosis, we're now ready to figure this out. Inheritance has a long history. The ancient Greeks were some of the first to give it serious thought; they has some interesting ideas (e.g., blending), but it wasn't until the mid 1800's that real progress was made. Gregor Mendel An Augustinian Monk working in Austria (today part of the Czech Republic). Had training in chemistry, physics & mathematics. Worked with garden peas to deduce how inheritance worked. Was experienced with these from childhood - AND he could control their breeding (i.e., which plant bred with which). Picked seven characteristics of pea plants to study how these characteristics were passed on from one generation to the next [OVERHEAD, fig. 9.2D, p. 155]. Started with pure breeding strains of plants For example, made sure he started with a plant that only produced purple flowers though several generations. Started by hybridizing these pure-bred strains. For example, what would happen if he crossed a plant that produced purple flowers with one that produced white flowers? Some terminology: P - parent generation F 1 - first offspring generation F 2 - offspring from F 1 etc. Single characteristics (in pea plants) [OVERHEAD, fig. 9.3A, p. 156]: Starting with plants that only produced purple flowers (pure strain purple) and plants that only produced white flowers (pure strain white): Mendel discovered that the F 1 generation was all purple (notice we're not saying they were a pure strain of purple).
What happened to white? Notice also that Mendel disproved the blending hypothesis that some people were considering (as far back as the Greeks). Mendel took the F 1 generation and bred it with itself (i.e., crossed plants from F 1 with other plants from F 1 ). Result was F 2, but in F 2, approximately ¾ of the flowers were purple, and ¼ were white. What was going on? Where did white suddenly come from? This should be no surprise - some of the characteristics about you may quite possibly come from your grand parents, and not your parents. Nevertheless, what's happening? Mendel developed four hypotheses based on his research. Mendel's four hypotheses: 1) There are alternative forms of heritable factors (what we now call genes). Alternative forms are called alleles. In our flowers we have two alleles for color, purple and white. 2) Each individual inherits two copies of these alleles. These may be two of the same (e.g., two alleles for purple), or two different ones (one for white, one for purple). If an individual has two of the same alleles, it is termed homozygous If an individual has two different alleles, it is heterozygous. 3) If the two alleles are different (the individual is a heterozygote), then one of the alleles will determine the individual's appearance. This is the "dominant" allele. The other allele essentially has no effect on the individual, and is called recessive. Note that this hypothesis is not always true (more later). 4) a gamete (sperm or egg) carries only 1 allele for each trait (because alleles separate from each other during production of gametes (meiosis)). Sometimes known as the law of segregation. When gametes come together (fertilization), there are again two copies of each allele. Mendel's explanation of the observed events [OVERHEAD, fig. 9.3B, p. 156]: Using Mendel's first two hypotheses, we can say:
One of the parent flowers (P plants) has two purple alleles, The other has two white alleles Thus, the gametes from the P generation are either P (purple) or p (white). (Note that unfortunately your text uses P for both the P generation and the P (purple) allele - they mean two different things). All the offspring from the parents got one P (purple) and one p (white). Putting these together, we use hypothesis 3 and conclude that the reason all the F1 plants are purple is due to the fact that P (purple) is dominant. p (white) is recessive. When looking at two alleles where one is dominant and the other recessive, we often use capital letters for the dominant allele, and lower case letters for the recessive. Finally, we can also explain the F 2 generation. We know that all the F 1 generation must have one P and one p (they're all Pp). Half of the sperm from F 1 will be P, half p. Similarly, half of the eggs will be P, and half p. If we now combine eggs and sperm, we can get four possible results: Egg with P and sperm with p (Result = Pp) Egg with P and sperm with P (Result = PP) Egg with p and sperm with p (Result = pp) Egg with p and sperm with P (Result = Pp) The Punnett square illustrates a better way of doing this (we put all possible sperms on one side, and all possible eggs on the other) I either case, notice we now have: ¾ purple (both PP and Pp are purple), and ¼ white (pp) Tis finally explains Mendel's results for F 2. Notice that the phenotypes and genotypes are different [OVERHEAD, not in book]. Phenotype - the physical appearance of our organism (Due to genetic AND environmental effects, though we won't worry too much about environmental effects right now). Our phenotype ratio is 3 purple : 1 white (¾ purple, ¼ white).
Genotype - the genetic makeup of our organism Our genotype ratio is 1 PP : 2 Pp : 1 pp (or ¼ PP, ½ Pp, ¼ pp). Mendel noticed that all of his other characteristics also worked the same way. Incidentally, statisticians have proved that Mendel cheated a little with his results. His results were better than one would expect (his ratios were way too good). Nevertheless, he had the right ideas, and interpreted his data correctly (he just made it look a little better). Some final remarks on Mendel: He published his results, which were promptly forgotten (Darwin had a copy, but didn't know what to do with it). He tried some crosses with animals (bees), but had difficulty controlling the crosses. Eventually he was elected abbot, and after that spent most of his time administrating the monastery. Mendel's research was eventually re-discovered and acknowledged about the turn of the century (1900). Review of gene loci [OVERHEAD, fig. 9.4, p. 157] Where are these alleles? Alleles for a particular trait are at the same loci on homologous chromosomes. Remember that during meiosis I, our homologous chromosomes go their separate ways, so our alleles go their separate ways (which is why Mendel's hypothesis 4 works). Working with more than one trait at a time [OVERHEAD, fig. 9.5A, p. 158]. Often, when we look at more than one trait, it turns out these traits are on different chromosomes (not homologous pairs). For example: Seed color (yellow and green) and seed shape (round and wrinkled) Y (yellow) is dominant, and R (round) is dominant (Mendel deduced this from previous crosses). So if we now take an individual that's homozygous for yellow and round (YYRR) and cross with an individual that's homozygous for green and wrinkled (yyrr), as expected, all the offspring are: YyRr (yellow and round).
Probability: Testcrosses: The question becomes, what happens when we cross this F1 generation with itself (YyRr x YyRr)? Two possible results. If Y and R always go together, and y and r always go together, we expect the results on the left hand side of the figure. (Four possible genotypes, two possible phenotypes) On the other hand, if Y and R each do their own thing (Y doesn't care what R is doing and vice versa), we get the result on the right hand side of the figure. (Nine possible genotypes, four possible phenotypes). The results were consistent with the second hypothesis. Thus we have the law of independent assortment. This states that each pair of alleles segregates (separates) independently of every other pair [OVERHEAD, fig. 9.16, p. 171]. (For some silly reason your text puts this figure no where near the previous one). As it turns out, this is only true if the traits are on different chromosomes (i.e., on non-homologous chromosomes). There are situations where this obviously doesn't hold. (Not all traits are independent). Remember - this is why we get many different combinations of chromosomes in our gametes (fig. 9.16). Another example is coat color in Labrador retrievers [OVERHEAD, fig. 9.5B, p. 159] How can we find out if someone is PP (purple) or Pp (also purple)? A testcross can be used. Cross the individual with a homozygous recessive: If the individual is PP, all offspring will be purple (why?) If the individual is Pp, ½ of the offspring will be purple, the other half yellow. [OVERHEAD, fig. 9.6, p. 159] uses our labs as an example. Be aware that most of what we're doing can be modeled using the laws of probability. I would love to go through this material (I'm a statistician after all!), but I don't see how it adds much to the discussion. Most of the problems here or in lab can be solved using Punnett squares & logic.
Human genetic traits: [OVERHEAD, fig. 9.8A, p. 161] Freckles / no freckles Widow's peak / no widow's peak Free earlobe / attached earlobe Important: notice that a dominant trait does NOT mean it's more common (Purple kernels are dominant in corn - how much purple corn is there?) More on this soon (when we do Hardy-Weinberg). Some of these human traits can be diseases (this topic also introduces family trees ) [OVERHEAD, not in book] A deaf boy was born to two normal parents. Deaf is recessive (in this kind of deafness) [OVERHEAD, fig. 9.9A, p. 162]. Implies that both parents were heterozygous (only in that way could Jonathan have inherited two recessive alleles). Also, notice that Jonathan had deaf children. He only passed on ONE allele for deafness. The other must have come from his wife. Implies that one of his wife's parents must have been heterozygous, but we can't say which one. Many genetic diseases are caused by a single gene (and one defective allele). [OVERHEAD, table 9.9, p. 163] Most serious genetic diseases are recessive If a genetic disease is dominant, it usually is not passed on to the offspring. Children die before being able to pass on the disease, so the disease does not survive. Recessive diseases can be carried without ill effects by heterozygotes. These are often termed carriers. But some dominant genetic diseases exist: Huntington's disease Does not strike until middle age. The parents have already had children, so the disease can be passed on. Inbreeding often increases the incidence of the disease
Expansions / variations on Mendel. Briefly, related individuals are more likely to both be carriers, and so pass on the disease to their children. This is easy to see with siblings, but even with 1st or 2nd cousins, the probability is still higher than normal. One can actually calculate this using some of the probability we skipped over. Mendel's hypotheses and laws do not account for everything. Some common exceptions: Incomplete dominance In this case, neither allele is dominant. The individual has traits in between the two alleles. The result is often a blending of the characteristics of both parents. [OVERHEAD, fig. 9.11A, p. 166] Flowers are red, white, or pink. BUT, in F 2, we get back to pure white or red, which wouldn't happen if the old blending hypothesis were correct. Blending pink and pink should yield just more pink. Hypercholesterolemia is another example HH -> normal Hh -> cholesterol levels about twice normal hh -> very high cholesterol levels. There is also co-dominance, where both alleles are expressed - the difference between this and incomplete dominance is subtle. Co-dominance means both alleles are expressed (the result is not in between ). Blood groups are an example. A and B are both expressed - blood type AB is not a mix of types A and B. More than two alleles and more on blood types and co-dominance: Many traits can have more than two alleles. Blood groups are a good example. There are three alleles: Type A, type B, and type O. Types A and B are dominant to type O:
AO & AA are essentially the same BO and BB are essentially the same OO is the only way to be type O Types A & B are co-dominant. People have some blood cells with type A characteristics, and some blood cells with type B characteristics. Note that AB is not a blending of types A and B. The reason one has to be careful with blood transfusions [OVERHEAD, fig. 9.12, p. 167]: Types A have cell identifiers for type A. Type B has different cell identifiers and is attacked. The same goes for type B (type A cells are attacked). In type AB, the body knows about both types of cells, so neither is attacked. Type O has no cell identifiers, so type O can be given to anybody (types A, B, or AB do not recognize O (no identifiers), and do not attack it). On the other hand, type O individuals will recognize both types A and B as foreign (type O individuals don't recognize any cell identifiers, so all cell identifiers are considered foreign). O is the universal donor, AB the universal recpipient. This presentation is just a little different than the book, but they both wind up in the same place (the book might be marginally more accurate, this might be a little easier to understand). Pleiotropy Simply put, this is where one allele will have multiple effects. [OVERHEAD, fig. 9.13, p. 168] Sickle cell anemia is a good example. Notice that this (as mentioned) is also an example of incomplete dominance. Heterozygotes are generally normal but much more resistant to malaria. Their cells will sickle under poor oxygen conditions, or when attacked by the malaria parasite (and the infected cells get destroyed!). Homozygous individuals either:
Don't get sickle cell (but get malaria) Get sickle cell (which is often fatal) We may mention this again when we do evolution, but being heterozygote is a distinct advantage. Malaria kills 2/3 of a million people every year. It's a strange situation, since both homozygote conditions are at a disadvantage. Many genes can influence a single character (kind of the opposite of pleiotropy). [OVERHEAD, fig. 9.14, p. 169] Three genes all contribute to skin color (book mentions it's at least three, maybe more). Environmental influences: Dominant in each case contributes some pigment. We can go from 0 to 6 (7 levels) of pigment. Environmental influences can determine a lot about our appearance Exercise, diet, altitude, sunlight, etc. (Mendel used characteristics that were generally not influenced by the environment). Genetic testing: There are many tests that can determine if some of these genetic diseases are present. Specific disease causing alleles can be detected. Depending on what is found, a couple may decide not to have children, for example (if both parents are carriers for a nasty disease). We need to be careful we don't use this information to make decisions about getting life insurance, etc. See also section 9.10 for more on genetic testing and some of the ethical issues raised. Exceptions to the law of independent assortment If the genes we are considering are on the same chromosomes, then independent assortment may not work as Mendel described. [OVERHEAD, fig. 9.17, p. 172] Purple and long pollen are on the same chromosome.
Crossing PpLl x PpLl did not yield the expected ratio of 9:3:3:1 Instead we got almost our 3:1 ratio of 3 purple-long: 1 red-round. P and L are on the same chromosome, and p and l are on the same chromosome, so we get 3 dominant : 1 recessive (a typical monohybrid cross). These are also known as linked genes. Crossing over produced the few exceptions to our 3:1 ratio. Review: [OVERHEAD, fig. 9.18A, p. 173] Crossing over was first hypothesized working with fruit flies: [OVERHEAD, fig. 9.18C, p. 173] A fly that was known to be heterozygous for two different traits (body color and wing length) was crossed with a fly recessive for both traits (black body and vestigial wings). A dihybrid cross in which the genes are on different chromosomes (independent assortment) would produce a 1:1:1:1 ratio: ¼ gray, normal, ¼ gray, vestigial, ¼ black, normal, ¼ black, vestigial. Instead, most (but not all!) of the flies were gray, normal or black, vestigial. The hypothesis was developed that these genes are linked (i.e. on the same chromosome), but that some mechanism sometimes broke the linkage to produce the other two varieties. This some mechanism was later shown to be crossing over. It turns out, crossing over can be used to identify the location of genes (to map genes). The further apart to genes (on the same chromosome) are, the more likely it is that they will undergo crossing over. If two genes are far apart, there are many points between them where crossing over can occur. If two genes are close together, there are only a few points between them where crossing over can occur. Incidentally, all points on a chromosome are not equally likely to be involved in crossing over, but the general principle holds. The greater the distance, the more likely crossing over will occur between genes.
Sex and chromosomes So, by looking at how often genes recombine through crossing over, we can get an idea of how far genes are physically apart on the chromosome. [OVERHEAD, fig. 9.19 A & B, p. 174]. As described, for many animals, chromosomes determine sex. In humans, we use X and Y (named due to the shape of the chromosomes). XY -> male, XX -> female [OVERHEAD, fig. 9.20 B - E, p. 175]. Other systems: A gene on the Y chromosome codes for the development of testes. The exact process is not yet understood, XX -> female, XO -> male (where O means no chromosome) Found in some insects like grasshoppers. Note that in both the XY and XO systems it's the male that determines sex: Sperm can be either X or Y (humans), or X or O (some insects like grasshoppers). ZW -> female, ZZ -> male In some birds, fish, butterflies. Notice that it is the female that has two different chromosomes. Therefore, it's the female that determines sex: Eggs can be either Z or W, males can only make sperm with Z. Some insects use chromosome number: diploid --> female, haploid --> male Some animals (some turtles, crocodiles) have temperature determined sex: The temperature of their eggs determines if the individual will be male or female. There is lots of variation in determining sex. And, of course, many organisms are hermaphrodites (have male and female parts); for them this is irrelevant.
Sex linked traits If genes (alleles) are being carried on the sex chromosomes, strange things can happen. In humans, for example, the Y chromosome does not carry many genes. So if genetic information is being carried on the sex chromosomes, men get only one allele (from the X chromosome). Genes carried on the sex chromosomes are often referred to as sex linked. Let's take a look to see what can happen. We'll look at fruit flies (again). White eyes is a recessive trait. Further, it's carried on the sex chromosomes (fruit flies have a XY system for determining sex). We have: X R X R -> red female X R X r -> red female X r X r -> white female X R Y -> red male (notice males only have one allele) X r Y -> white male As you might expect, it's easier to get white males than white females. Three examples [OVERHEAD, fig. 9.21 B - D, p. 176]: Crossing X R X R with X r Y: ½ X R X r, ½ X R Y (All males must get X R from the mother) Crossing X R X r with X R Y ¼ X R X R, ¼ X R Y, ¼ X r X R, ¼ X r Y (Notice that only males can be white, for a female to be white, she MUST get X r from the father (the father does not have X r )).
Crossing X R X r with X r Y ¼ X R X r, ¼ X R Y, ¼ X r X r, ¼ X r Y (This time, the female offspring can get one X r from the mother and one X r from the father, so we do get white females). Due to this phenomenon, sex linked recessive traits show up more commonly in males than in females (males only need one recessive allele, females need two). If this trait is also a disease, this can have devastating consequences for males (they're more likely to get the disease). Red-green color blindness is more common in men One type of hemophilia is more common in men [OVERHEAD, fig. 9.22, p. 177] Duchenne muscular dystrophy is more common in men A disease that causes muscle weakening and loss of coordination. Often fatal by the early 20's (in age). All three diseases are more common in men because all three are carried on the sex chromosome (the X chromosome, not the Y).