A. What is meiosis for?

Most of the cells of most higher organisms are diploid. Humans, for example, have 46 chromosomes, or 23 pairs, in virtually all of their cells. If eggs and sperm also have 46 chromosomes, the next generation, formed from the fusion of an egg and a sperm, would have 92 chromosomes. But clearly the chromosome # does not double each generation. So the eggs and sperm, unlike all other cells, must have only 23 chromosomes and be haploid. So there must be a way to make haploid cells from diploid cells. There is, and the process is called meiosis. During meiosis, one chromosome from each pair is picked at random so that the resulting haploid has 23 chromosomes instead of 23 pairs. Then 2 such haploids fuse, during fertilization, to give you back a diploid with 23 pairs.

       3. How reshuffling works

    B. What happens to chromosomes during meiosis?  -- see Handout 19B

        1. DNA synthesis occurs first -- before division. Meiosis is preceded by DNA duplication just as mitosis is. During the S before meiosis (or mitosis) the cell doubles the DNA content and # of chromatids per chromosome. So cell starts with pairs of doubled chromosomes = 4 copies of each chromosome.

        2. Products:  There are 4 products, each haploid (from meiosis), instead of 2 products, each diploid (from mitosis). To cut the number of copies of each chromosome from 4 to one requires 2 division, not one.

        3. Two divisions of meiosis: The first division of meiosis separates homologs; the second division of meiosis separates sister chromatids.

        4. What happens to N, c and # of chromatids/chromosome? The first division cuts the chromosome number per cell in half from 2N to N and cuts the DNA content per cell in half from 4c to 2c ("c" is defined below). The second division halves the DNA content per cell (from 2c to c),  halves the number of chromatids/chromosome (from 2 to 1) and halves the total chromatid # per cell (from 2N to N). What happens in a cell with one pair of chromosomes is as follows:

    B. Definition of c

"c" is a measure of DNA content per cell, not the number of chromosomes or chromatids.

c = minimum DNA content per haploid cell of an organism = DNA content of haploid cell before S (with unreplicated chromosomes) = DNA content of one set of chromatids. C is NOT equal to N; c is the DNA content of N chromosomes (with one chromatid/chromosome).

To review Meiosis (so far), and compare to Mitosis, do or finish problems 8-1, 8-2 (parts A to E),  8-3, & 8-8 (parts A-D & G). Details of meiosis next time or see handout 19A.

    A. Steps: These are diagrammed in detail on handout 19A, and comparisons to mitosis are summarized there. For similar diagrams of mitosis vs. meiosis see Purves 9.17 or Becker fig. 20-9 (18-9). For nicer pictures see Purves 9-14 or Becker 20-5 & 20-6 (18-5 & 18-6).

    B. What if N >1? Handout 19A shows what will happen to a cell with 1 pair of chromosomes. (2N cell, N =1.) If there are additional chromosome pairs (N > 1), each pair will line up independently at metaphase I. This has important genetic implications, as will be discussed later.

    C. Prophase I -- Some Differences from Mitosis

        1. Crossing over. This is the time when recombination occurs by a "cut & splice" mechanism, which switches equivalent sections of chromosomes between 2 members of a pair. Recombination requires pairing, so homologous chromosomes are paired in pro. I of meiosis but not mitosis.  More details to follow. (Pictures of pairing are shown in the texts.)

        2. Duration.  Prophase I in meiosis is generally much longer and more complex than prophase in mitosis. (Both texts divide prophase into early, mid and late substages; Becker 20-7 (18-7) has even more details if you are curious.) Pro. I can be very prolonged -- in human females, it lasts from before birth to the time the egg is shed. Consequences of this very long pro. I will be discussed next time. 

    D. Products of human meiosis (see Purves 43.3 (42.4) or Becker fig. 20-10 [18-10])

        1. In Females: When female germ cells go through meiosis, the equivalent of 4 haploid nuclei are formed, but only one ends up in an egg. The genetic material that would end up in the "other 3" nuclei is shunted aside --it forms small structures called polar bodies. The egg contains (at least) the amount of cytoplasm that would be sufficient for 4 meiotic products and the genetic information of only one. 

        2. In males: When male germ cells go through meiosis, 4 sperm are formed.

    A. Supercycle -- Handout 20B.

        1. General idea -- Overview

    Many different life cycles are possible, depending on the number of mitotic divisions that follow meiosis and/or fusion. The diagram on the top of handout 20 labeled "Supercycle" shows a generalized life cycle and explains the terminology. (Purves 9.12 or 29.2 is equivalent; Becker fig. 20-4 [18-4] is similar.) If an organism goes through all the stages shown, then it has both haploid and diploid phases.

        2. Haploid vs Diploid Life Cycles 

            a. Diploid Life Cycle. What you get if meiosis → gametes. (No mitotic division of haploids).

            b. Haploid Life Cycle. What you get if the zygote divides immediately by meiosis, not mitosis. (No mitotic division of diploids.)

       3. Alternation of Generations 

• Most plants go through both haploid and diploid phases, with mitotic divisions of both haploids and diploids. However the haploid phase is so short (involves so few mitotic divisions) that the haploid form of the organism is usually not visible to the naked eye.
• Both phases may be visible.  A few of the simpler plants, such as moss, produce both haploid and diploid forms that are visible to the naked eye.  See Purves 29.5 & 29.9 (28.3 & 28.7) and/or Becker fig. 20-4 (c) [18-4 (c)]. You can see both the sporophyte (spore bearing form of plant) and the gametophyte (gamete bearing form of plant).
• For moss, the green fuzzy stuff  is haploid and produces gametes, so it is called the gametophyte = gamete-bearing plant. Two gametes fuse to form a zygote, which divides by mitosis to produce the brown stalks (diploid) on top of the green mat. Some cells of the stalk go through meiosis to produce spores (inside the capsule at the end of the stalk), so the stalk is called a sporophyte = spore-bearing plant. 

        4. Super cycle can reduce to haploid or diploid life cycle           

            a. Diploid Life Cycle. If meiosis → gametes (no spores; no mitosis of haploids), the organism has really skipped most of the stages on the left half of the supercycle diagram and gone directly from germ cells to gametes. Such an organism has a basically diploid life cycle, as humans do. See Becker, fig. 20-4 (d) [18-4 (d)]. 

            b. Haploid Life Cycle. An organism can skip most of the right half of the diagram if the zygote divides immediately by meiosis, not mitosis. (No mitosis of diploids. No germ cells.) Such an organism has a basically haploid life cycle. Some simple algae are like this. See Becker fig. 20-4 (b) [18-4 (b)].

          4. Gametes and Spores -- Terminology

• Two ways to get gametes --  by meiosis of 2N or specialization of N cells. Moss produces gametes by specialization of haploid cells; humans produce gametes by meiosis of diploids.
• Products of meiosis can be spores or gametes. In moss, the products of meiosis are called spores, not gametes, because the meiotic products are going to divide by mitosis (before specializing to make gametes). In humans, the products of meiosis are called gametes.
• Gametes vs spores: If meiotic products will never divide by mitosis, but simply fuse to form a zygote, then they are called gametes. If the meiotic products are going to divide by mitosis, then they are called spores. {Q&A}

    B. Some implications of this cycle:

        1. The Problem of Development. If zygote→ us by mitosis; how does development work? If all cells have the same DNA, why do cells make different proteins? In other words, why are the genes 'expressed' differently in different cell types? What sets and maintains the switches? How differential gene expression is set up and maintained is not entirely understood, but will be discussed some more next term. 

        2. Amniocentesis. If all cells of fetus have same genes/DNA/chromosomes, you can test the DNA or chromosomes of any fetal cell to look for abnormalities, even if the gene involved only affects (makes proteins in) certain specialized tissues. If you identify a fetus that will have sufficiently serious disabilities, you have the option to consider a therapeutic abortion. There are several current ways to test fetal cells, and more ways are under development. The most common current method is  amniocentesis (testing fetal cells from amniotic fluid). Some examples: these will not be discussed in class but are included FYI.

            a. Gene Mutations. You can look at DNA sequence (by PCR, use of probes, etc) for smaller changes affecting one or a few genes and/or nucleotides (so called "gene" mutations). Sometimes you can look at the protein the gene makes as in case (1) below, but sometimes you have to look at the DNA instead as in case (2). Some examples:

                (1). Tay-Sachs disease. The gene that causes Tay-Sachs disease (when mutant) codes for an enzyme. The enzyme is made in many cell types, including the cells in the amniotic fluid. Using amniotic fluid cells, you can look at the DNA or measure the enzymatic activity of the protein made from the gene. 

                (2). PKU. The gene that causes phenylketonuria or PKU (when mutant) codes for an enzyme that is made only in liver cells. So using amniotic fluid cells, you can't measure the activity of the enzyme.  But you can test the state of the gene itself (in amniotic fluid cells) to see if the gene is normal or mutant. 

            b. Chromosome Mutations.  Since you can do banding, you can tell all the chromosomes and chromosome regions apart. Therefore you can detect large abnormalities affecting whole chromosomes and/or large blocks of genes (so called "chromosomal" mutations) from looking at karyotypes as discussed previously.

 To review life cycles, cell cycle, etc. and how they all fit together, try 8-11 and/or 8-14.

    A. Where do individuals with missing and extra chromosomes come from?

    Answer: Mistakes in Meiosis. Two types of mistakes:

• Homologs can fail to separate (fail to "disjoin") properly at first division (= 1st div. nondisjunction), or
• Sister chromatids can fail to separate properly at second division (= 2nd div. ND).

Either way, nondisjunction gives gametes with extra and/or missing chromosomes (aneuploidy). See handout 20B, bottom half of page. When an aneuploid gamete (= gamete with missing or extra chromosomes) from one parent meets a  normal gamete from another parent, then a monosomic or trisomic zygote is formed. The zygote can divide by mitosis to produce an aneuploid individual. Aneuploid zygotes containing missing or extra autosomes usually do not develop into viable individuals, but aneuploid zygotes containing missing or extra sex chromosomes (XO, XXY, XXX etc.) are usually viable as long as there is at least one X. (Why is this? See below.)

    On handout 20B: Note that second division ND can involve either the "straight" or the "wiggly" chromatids, but only one case is shown. Also note that the "empty" cell is not really empty -- it is only missing a chromosome from the pair involved in ND. It has all the other chromosomes, but they are not shown to keep the picture as simple as possible. ND is an error than generally affects only one event at a time -- one pair of chromatids or one pair of homologs fails to separate at one stage of meiosis. usually all other separations of chromosomes and chromatids usually proceed normally. See Purves 9.18. 

    B. What types of aneuploidy are common? See lecture 19 for details.

        1. Trisomy 21.

        2. Aneuploidy of the sex chromosomes. 

    A. Lyon Hypothesis = inactive X Hypothesis

    B. Barr bodies

    You can actually see the inactive X during interphase because it forms a Barr body. There are 2 X chromosomes in every female cell, but (according to the inactive X hypothesis) only 1 of them works (is transcribed) most of the time. In general, if there are extra X chromosomes, all the extras are inactive, whether the cell is male or female. The inactive X's remain tightly coiled during interphase and are called Barr bodies. (So you can tell the sex of the cell without doing a karyotype.) Note that inactive X chromosomes are replicated, but not transcribed.

    C. How is mosaic detected? Intro. to Genetic Terminology
 

    Consider coat color in cats. This is how Lyon actually figured out the inactive X existed. In cats, a gene controlling coat color is on the X. The position of the gene is known as the locus of the gene. This gene has two alleles (alternate forms); one → black coat color and the other → orange. One of the alleles is present at the coat color locus on every X. The Y chromosome does not carry an allele of the coat color gene. 
    Males have only one X, which carries either the black or the orange allele, so normal male cats are all black or all orange. (They may have regular stripes, superimposed on the black or orange, but the background color is either all black or all orange -- they don't have areas of orange and areas of black).
    Females have two X's, so they carry two alleles of the coat color gene -- one on each X. A female can be homozygous black (have 2 black alleles), be homozygous orange (have 2 orange alleles), or be heterozygous (have one allele of each color), as shown in figure. Females can be orange, black or patchy (with areas of each color). Only heterozygous females are patchy.
    All this makes sense if only one copy of the X works in each patch so only one copy of the coat color gene works per cell (and per patch). Rare patchy males are XXY (Klinefelter's Kats).

Note "Patchy" is called tortoise shell, not tabby; calico = patchy plus white. (Tabby = regular pattern of stripes that occurs in both males and females.)


    D. When do Barr bodies form? How do you get the mosaic?

    Fertilized egg (zygote) → ball of cells → each cell inactivates one X at random → each cell divides by mitosis → descendants with same X on/off. Once an X is inactivated, it generally remains inactivated through succeeding mitoses, so all mitotic descendants of a single cell have the same X on and the same X off → all cells in one area (or with same lineage) have same X on/off. Germ line cells (which will go through meiosis) turn both X's back on before gametes are made (before meiosis occurs. So either one of the two X chromosomes can be used or inactivated in the next generation.

To review Genetic Terminology so far, try 8R-1. (Also see Becker fig. 20-2 [18-2].)