mutation

VI. Mutations: changes in the genome

Overview - changes in the genome can occur at four scales.

1. There can be an addition or loss of an entire set of chromosomes - CHANGING PLOIDY (THIS IS THE BIGGEST CHANGE POSSIBLE)
2. Within a set, there can be the gain or loss of a chromosome - CHANGING ANEUPLOIDY (trisomies and monosomies)
3. Within a chromosome, there can be a gain or loss of GENES - DELETIONS/DUPLICATIONS
4. Within a gene, there can be the gain, loss, or change of a nucleotide - POINT MUTATION (THIS IS THE SMALLEST CHANGE POSSIBLE), or a changing of exons within a gene.

Mutations only occur in living cells (dead cells don't replicate their DNA or divide, and that is when mutations occur). So, since a living cell already works, it is likely that a mutation (which is usually a random change) will 'hurt' the cell rather than help it. Of course, "it is likely" does NOT mean "always". So, most mutations are 'bad' for the cell and organism, but some mutations can be neutral or beneficial. Now, since the cell already works, a LARGE change is likely to be worse than a small change. Think about a car that runs. If you make a big change to the system, like taking out the engine, or putting one big wheel on, it is likely to have a greater negative effect than a small change (such as changing the direction of the rear-view mirror). So, let's look at these types of changes.

A. A Change in Ploidy

- the # of SETS of chromosomes

1. Mechanism #1 - Complete failure of Meiosis

a. process

- There is no reduction; a diploid gamete is produced. This can occur as a failure to divide during meiosis I or meiosis II, as shown in class.
- It is unlikely that this rare event would occur in two different individuals at the same time, so typically this diploid gamete will fertilize a normal haploid gamete, resulting in a TRIPLOID (3n) zygote.

b. result

a diploid gamete is produced.
usually, this gamete is fertilized by a normal haploid gamete, resulting in a triploid zygote.
this is almost always BAD - especially in animals - resulting in the inability of the zygote to develop correctly and the spontaneous abortion of the embryo.
- Triploidy is usually a reproductive dead-end, because triploids can't produce gametes by meiosis (how do you divide 3n equally?).
- But, there are triploid species; they have gotten around this by reproducing parthenogenetically - without fertilization. They produce gametes by mitosis, without reduction (just like THEY were probably produced...suggesting some possibility of a heritable aspect to this mistake). These 3n eggs develope without fertilization into 3n adults... clones of the original female parent. (All triploid lineages that survive in this way are females).
- So, when this happens, a new unique lineage is created that does not exchange genes with any other group... it is a new 'instant' species.

2. Mechanism #2 - Failure of Mitosis

- In hermaphroditic species (have both male and female parts), a mitotic mutation may affect both the male and female gamete-forming tissues.

- For instance, consider a flower bud. If a diploid cell has the chromatids separated but does not actually split into two separate cells, then the cell has doubled its genetic information and has gone from a 2n cell to a 4n cell.

- Now, suppose it divides correctly from this point forward. The flower produced from this cell consists of 4n cells.

- So, in the anther and ovary where sperm and eggs are produced, the gamete-forming cells are also 4n. When they proceed through meiosis, they will produce 2n gametes.

- Here, however, there are 2n male AND 2n female gametes produced. If the plant is self-fertile, these sperm can fertilize these eggs and a 4n zygote will be produced. This is TETRAPLOIDY. - Tetraploid offspring may not survive; there may still be enough of a disruption in the protein concentrations to screw-up development. But, if they can survive, then they WILL be able to make gametes by normal meiosis. Their 4n cells CAN divide evenly, producing 2n gametes.

- This lineage could reproduce itself, and would be reproductively isolated from its originating species because IF their 2n gametes fertilized the haplid gametes of the originating species, the 3n triploid would be produced, which is typically a reproductive dead-end.

3. Frequency of Polyploidy

- Polyploidy (>2n) is VERY rare in birds and mammals. The only 4n species of mammal is a small mouse that lives in the Andes - its was discovered in 2002. No birds are known to be triploids. However, it is more frequent (but still rare) in fish, amphibians, and reptiles, where there are parthenogenetic 3n sister species of normal 2n species. However, on the whole, polyploidy is rare in dioecious species (where individuals are EITHER male or female). This is probably because the most likely product in these species is a triploid, which has the sterility problems mentioned earlier.

- In plants and other hermaphroditic (or "monoecious") species, polyploidy is FAR more common. This is probably because tetraploidy is far more likely, and the tetraploid will be fertile. In fact, about 30-50% of all flowering plant species are polyploid!!!. That means that this mechanism has been a pretty important source of new species!!! Some genera (species in the same genus) have species with sequential increases in ploidy. For instance three different species of goldenrods have 14, 28, and 56 chromosomes, respectively. So, a reasonable hypothesis is that the second and third species were formed through polyploid events (failure in mitosis) as described above.

B. Changes in Chromosome Number

- this is the loss or addition of single chromosomes, not whole sets of chromosomes.

1. Mechanism: Non-disjunction

- During meiosis, homologous chromosomes fail to segregate; both go to one daughter cell. So, we end up with a gamete with an extra chromosome and one which has lost a chromosome.

- when fertilization occurs with a normal haploid gamete, we end up with a zygote with an extra chromosome - a third chromosome in one homologous 'pair'. (Remember, one gamete inherited BOTH homologs, and then the other parent correctly contributed a single chromosome for this set.) So, this situation is called a "TRISOMY" (three bodies.)

- if the other aberrant gamete is involved, we end up with a zygote with one too few chromosomes - this is a monosomy.

2. Human Conditions

In humans, these imbalances are almost always fatal to the developing embryo - they are usually spontaneously aborted during development (the vast majority of spontaneous abortions have chromosomal anomalies). However, some can complete development to birth and beyond. When this occurs in the #21 chromosome, we can produce TRISOMY 21...Downs Syndrome. Trisomies in the sex chromosomes are also tolerated, resulting in XXX, XXY, and XYY offspring.

- In humans, the only human monosomy that does, periodically, survive to birth and beyond is the monosomy for the sex chromosome, with 1 X chromosome.

- Karyotypes: we write a human genotype as follows: 1) total number of chromosomes 2) complement of sex chromosomes 3) any imbalance
So, a female with Down's Syndrome is: 47,XX, +21

Study questions:

- Describe two mechanisms by which polyploids can be produced.

- How can polyploidy create a new species?

- Why are tetraploids more likely to establish a productive population than triploids?

- Describe how trisomy-21 is produced by non-disjunction.

- Why are trisomies and monosomies usually bad?