2013 年 12 月 – AP Biology

Genetics [10] reproduction 3: Meiosis 2

Last section we gave a general introduction of meiosis in terms of chromosome behaviors.

In this section, we will deal with two other respects of meiosis. First, a specific description of meiosis in animals; second, we will mention a situation when meiosis goes wrong.

Meiosis in animals

is found only in ovaries (卵巢)and testes(曲细精管), and even in these tissues is restricted to cells that are destined to form gametes(the germline).

Despite the fact that the mechanisms of gametogenesis differ somewhat between organisms,the steps involved in gametogenesis in mammals are relatively similar.

In male gametogenesis (spermgenesis).

precursors of germ cells go through many rounds of mitotic divisions in order to maintain a pool of spermatogonia(plural of spermatogonium 精原细胞).↓

Spermatogonia subsequently differentiate into primary spermatocytes(based on what you learned in high school. guess what this word mean? : D ). It is in these cells that meiosis takes place.↓

After meiosis I, these cells are referred to as secondary spermatocytes. These are haploid. The products of the second meiotic division are spermatids. ↓

Spermatids differentiate into motile spermatozoa with rounded or elongate head and a long posterior flagellum.(The final activation of spermatozoa takes place after copulation/sexual intercourse)

Without cytoplasm and many subcelluar organelles, the sperm is light and fast (almost all its weight concentrated in its head, where stored the key of a potential life, nuclei. ).

In female mammals, the pattern of oogenesis is superficially similar.

Here oogonia(plural of oogonium, 卵原细胞) go through mitotic divisions before differentiating into primary oocytes. These then undergo meiosis.↓

Both daughter cells of the primary oocytes are haploid but differ greatly in size. The larger daughter cell is the secondary oozyte, the smaller the first polar body. The two cells remain attached. Both undergo a second meiotic division.↓

The secondary oocyte undergoes an unequal division producing a large ovum and a small secondary polar body. The first polar body divides into two secondary polar bodies.

Only the ovum, which contains almost all the cytoplasm, will transmit genes into the next generation.

The first meiotic division is only completed at ovulation(the discharge of a mature ovum from the ovary), and the second occurs after fertilization.

Little known: In human females, primary oocytes can be held in meiotic arrest for up to 45 years. This may be important in the increased frequency of aneuploid births observed in older mothers.

Production of aneuploid gametes

The major cause of anueploidy(the situation of having or being a chromosome number that is not an exact multiple of the usually haploid number) is aberrant chromosome behavior at meiosis. In other words, it’s the failure of chromosmes to segregate properly(known as nondisjunction)

At anaphase I, if two homologous chromosomes move to the same pole, first division nondisjunction occurs. In this case, of the 4 cells arsing from meiosis, two will be disomic(contain two copies of the chromosome) and two nullisomic (contain no copy of the chromosome.

At anaphase II, if the chromatids in a cell remain together, division nondisjunction occurs. The resulting tetrad will contain two normal cells, one nullisomic, and one disomic.

Aneuploidy also arises due to nondisjunction at an early mitosis in the embryo, resulting in two populations of cytogenetically different cells in the individual, which is known as a mosaic.

MOSAIC (GENETICS)"Heterochromia iridum and iridus" image from simple.wikipedia.org — MOSAIC (GENETICS)”Heterochromia iridum and iridus” image from simple.wikipedia.org

Mosaic is common in Turners syndrome.

↑Turner syndrome or Ullrich–Turner syndrome is a chromosomal abnormality in which all or part of one of the sex chromosomes is absent or has other abnormalities . In some cases, the chromosome is missing in some cells but not others, a condition referred to as mosaicism or “Turner mosaicism”.

Occurring in 1 in 2000– 1 in 5000 phenotypic females, the syndrome manifests itself in a number of ways. There are characteristic physical abnormalities which affect many but not all people with Turner syndrome, such as short stature,swelling, broad chest, low hairline, low-set ears, and webbed necks. Girls with Turner syndrome typically experience gonadal dysfunction (non-working ovaries), which results in amenorrhea (absence of menstrual cycle) and sterility. Concurrent health concerns may also be present, including congenital heart disease, hypothyroidism (reduced hormone secretion by the thyroid), diabetes, vision problems, hearing concerns, and many autoimmune diseases.Finally, a specific pattern of cognitive deficits is often observed, with particular difficulties in visuospatial, mathematical, and memory areas.

Turner syndrome is named after Henry Turner, the endocrinologist who first described it in 1938.（wikipedia）

the blueprint of life [10]: eukaryotic structure of DNA 3

let’s go over the terms again. Make sure you all know what they mean.

•Nucleus: 细胞核; Nucleolus: 核仁; Nucleoid: 类核

• Mitosis: 有丝分裂; Meiosis: 减数分裂

Interphase: 分裂间期; Prophase: 分裂前期; Metaphase: 分裂中期; Anaphase: 分裂后期; Telophase: 分裂末期

• Histone: 组蛋白

• Nucleosome: 核小体

•Chromosome: 染色体; Chromatin: 染色质; eu- 真染色质; hetero- 异染色质

Sister chromotid 姐妹染色单体;
mitotic spindle 纺锤体
spindle microtubule纺锤丝

• Centromere: 中心粒; Telomere: 端粒

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The familiar picture of a chromosome is actually that of the most highly condensed state at mitosis(which we reviewed in the blueprint of life [8]: eukaryotic structure of DNA 1(chromatin structure)).

As the daughter chromosomes are pulled apart by the mitotic spindle at cell division, the fragile centimeters-long chromosomal DNA would certainly be sheared by the forces generated, were it not in this highly compact state.

picture above is from Instant Notes in Molecular Biology

As we can see from the picture, the chromosomal loops fan out from a central scaffold or nuclear matrix region consisting of protein(which we talked about last section). One possibility is that consecutive loops may trace a helical path along the length of the chromosome.
The centromere is the constricted region where the two sister chromatids are joined in the metaphase chromosome. This is the site of assembly of the kinetochore, a protein complex which attaches to the microtubules of the mitotic spindle.

(The microtubules act to separate the chromotids at anaphase)

The DNA of the centromere has been shown in yeast to consist merely of a short AT-rich sequence of 88 bp, flanked by two very short conserved regions, although in mammalian cells, centromeres seem to consist of rather longer sequences, and are flanked by a large quantity of repeated DNA, known as satellite DNA.

Telomeres are specialized DNA sequence that form the ends of the linear DNA molecules of the eukaryotic chromosomes. A telomoere consists of up to hundreds of copies of a short repeated sequence(5′-TTAGGG-3′ in humans), which is synthesized by the enzyme telomerase in a mechanism independent of normal DNA replication.

The telomeric DNA forms a special secondary structure, the function of which is to protect the ends of the chromosome proper from degradation.(Independent synthesis of the telomere acts to counteract the gradual shortening of the chromosome resulting from the inability of normal replication to copy the very end of a linear DNA molecule—we will talk about this when reaching DNA replication)

Interphase chromosome

In interphase(S phase, to be exact), the genes on the chromosomes are being transcribed and DNA replication takes place. During this time, the chromosmes adopt a much more diffuse structure and cannot be visualized individually. It is believed, however, that the chromosomal loops are still present, attached to the nuclear matrix.

The blueprint of life [9]: eukaryotic structure of DNA 2(nucleosome)

Eukaryotic chromosome is packaged in hierarchical levels, mediated by various proteins.

DNA duplex→Nucleosome → Chromatin →Chromosome

We talked about DNA duplex and chromatin; now it’s time to meet the basic unit of chromatin structure–nucleosome.

Definition: nucleosome is the chromatin subunit that consists of DNAand a set of eight histone core proteins(complex of (H2A)₂(H2B)₂(H3)₂(H4)₂, →octamer. More loosely with one molecule of H1 )

Comparison

The proteins protect the DNA from the action of micrococcal nuclease.

Micrococcal Nuclease is an endo–exonuclease that preferentially digests single-stranded nucleic acids The enzyme is also active against double-stranded DNA and RNA and all sequences will be ultimately cleaved.(wikipedia)

Digestion with nuclease leads to the loss of H1, yielding a very resistant structure consisting of 146 bp of DNA associated very tightly with the histone octamer. The structure, known as the nucleosome core, is structurally very similar whatever the source of the chromatin.

Adjacent nucleosome is connected by a varied length (10-100 bp, average 55bp)of DNA, called “linker DNA”

One molecule of linker histone H1 binds to the linker DNA between nucleosome.

H1 also acts to stabilize the point at which the DNA enters and leaves the nulceosome core.

↑Chromatins at different packaging levels

30 nm chromatin fiber: condensed form

10 nm chromatin fiber : less-condensed form, like a thread of beads

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Summary of Nucleosome Structure:

NUCLEOSOME STRUCTURE, image from bricker.tcnj.edu

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Higher Order Structure

The organization of chromatin at the highest level seems rather similar to that of prokaryotic DNA(see THE BLUEPRINT OF LIFE [7]: PROKARYOTIC CHROMOSOME STRUCTURE OF DNA). Even the size of the loops is approximately the same, up to aorund 100 kb of DNA, although there are many more loops in a eukaryotic chromosome.

The loops are constrained by interaction with a protein complex known as the nuclear matrix. The DNA in the loops is in the form of 30 nm fiber, and the loops form an array about 300 nm across.

”Solenoid model “of 30-nm chromatin fiber

6 nucleosomes per turn

“Zigzag model” of 30-nm chromatin fiber

6 nucleosomes per turn, longer linker DNA may be required

HIGHER ORDER STRUCTURE, shown by prof. Dong

Genetics [9] Reproduction 2: Meiosis

During the process of reducing the number of chromosomes by half, the combination of alleles are rearranged to give recombinant gametes. Two distinct processes are involved. These are independent assortment of chromosomes and crossing-over.

Meiosis involves twosuccessive divisions, resulting in producing four cells, each containing half the number of chromosomes of the mother cell. There is NO replication between the two divisions.

We call the two divisions meiosis I and meiosis II, as in Chinese 减数第一次分裂 and 减数第二次分裂. Here we will introduce more of meiosis than meets in high school textbooks.

Meiosis I

meiosis I is divided into prophase, metaphase, anaphase and telophase. Although they have the same names as the four phases in typical mitosis, behavior of chromosomes in these four phases in meiosis is very different from that in mitosis.

In prophase each chromosome pairs with its homolog (copy of the same chromosome inherited from the other parent). The paired chromosomes are called bivalents. Each pair is held together by chiasmata(plural of chiasma). The exchange of genetic material is known as crossing-over.

A chiasma (plural: chiasmata), in genetics, is thought to be the point where two homologous non-sisterchromatids exchange genetic material during chromosomal crossover during meiosis (sister chromatids also form chiasmata between each other, but because their genetic material is identical, it does not cause any change in the resulting daughter cells). (from wikipedia)

Prophase of meiosis is subdivided into five stages: leptotene, zygotene, pachytene, diplotene, and diakinesis.
In leptotene(literal translation:thin threads), the chromatin is seen to condense into very long thin strands, that appear tangled in the nucleus. As prophase proceeds chromosomes become shorter and thicker.
At zygotene(literal translation: yoked/linked threads), homologous chromosomes are seen as partially paired structures. They are still very elongated at this stage and chromosome pairs may overlap or interwine.
By patchytene(thick threads), pairing is complete, though it still isn’t possible identify clearly the individual chromatids in each bivalent.
As the homologous chromosomes begin to separate, transition from patchytene to diplotene(double threads) occurs.

This process begins at the centromeres and the bivalents are seen to be held together by chiasma.

The nuclear membrane and the nucleolus breaks down.

The four chromatids in each bivalent become identifiable and individual chiasma clearly to be identified.

Chromosomes carrying on condensing, the cell moves into diakinesis(moving apart), the final subdivision of prophase I.

The scheme below shows the five stages in prophase in a simple way:

At metaphase I the nuclear envelope breaks down, the bivalents lie across the equator of the cell with their centromeres attached to the microtbules←similar to the spindle in mitosis.

The dynamic action of the spindle causes one member of each homologous cell to move to the opposite poles of the cell.

↑WHY wouldn’t the action of the spindle tear apart the sister chromatids?

BECAUSE at metaphase the sister chromatids are held together by proteins called cohesions, which holds chiasmata in place and so holds the chromosomes together.

At anaphase I the cohesions in the chromosome arms are cut, allowing the homologs to separate.

In telophase I, two neclei form around the segregating chromosomes and a degree of chromosome decondensation is observed.

Meiosis II

The process of meiosis II closely resembles that of the typical mitosis.

In prophase II the chromosomes are seen to recondense within the two nuclei. At metaphase II, the nuclear membrane breaks down and chromosoms rearranged at the equator , the centromere splits and…At anaphase II and telophase II,the initial dipliod cell has divided into four…we already knew these in high school.

What we didn’t know in high school is that each of the four haploid cells has a different genotype. And in many instances the group of four haploid cells may remain together and is known as a tetrad.

SUMMARY OF MEIOSIS

Genetics [8]：reproduction 1

Reproduction takes place by one of two methods, asexual or sexual.

Asexual reproduction involves the production of a new individual(s) from cells or tissues of a pre-existing organism. This process is common in plants and in many microorganisms. It can involve simple binary fission(splitting into two) in unicelluar microbes or the production of specialized asexual spores(孢子).

NATURAL VEGETATIVE PROPAGATION. New plants grow from parts of the parent. (image from: leavingbio.net)

These processes may be exploited for commercial purposes as in the vegetative propagation of plants. More recently it has been possible to regenerate whole organisms from a single cell. This was first shown in carrots and frogs, but it has now been reported in mammals, and by implication, is possible in all mammals including humans.

Asexually reproduced organisms are genetically identical to the individual from which they were derived. A group of such genetically identical organisms is known as a clone.

Here I found an article at Buzzle , thinking it may help us learn more about animal cloning: http://www.buzzle.com/articles/animal-cloning/. Below is an excerpt of that article.

1, The Process of Animal Cloning
Initial attempts at artificially induced Animal Cloning were done using developing embryonic cells.

The DNA nucleus was extracted from an embryonic cell and implanted into an unfertilized egg, from which the existing nucleus had already been removed. The process of fertilization was simulated by giving an electric shock or by some chemical treatment method. The cells that developed from this artificially induced union were then implanted into host mothers.

The cloned animal that resulted had a genetic make-up identical to the genetic make-up of the original cell←the embryonic cell that contributes the DNA nucleus.

Since Dolly, of course, it is now possible to create clones from non-embryonic cells.

Now animal cloning can be done both for reproductive and non-reproductive or therapeutic purposes. In the second case, cloning is done to produce stem cells or other such cells that can be used for therapeutic purposes, for example, for healing or recreating damaged organs; the intention is not to duplicate the whole organism.

2. Ethics of Animal Cloning
While most scientists consider the process of animal cloning as a major break through and see many beneficial possibilities in it, many people are uncomfortable with the idea, considering it to be 'against nature' and ethically damning, particularly in the instance of cloning human beings.

The truth is that most of the general public are not aware of the exact details involved in cloning and as a result there are a lot of misconceptions about the entire matter.

In recent times, there have been a spurt of new laws banning or regulating cloning around the world. In some countries, animal cloning is allowed, but not human cloning. Some advocacy groups are seeking to ban therapeutic cloning, even if this could potentially save people from many debilitating illnesses.

3. Points against Animal Cloning
In a large percentage of cases, the cloning process fails in the course of pregnancy or some sort of birth defects occur, for example, as in a recent case, a calf born with two faces. Sometimes the defects manifest themselves later and kill the clone.

4. Points for Animal Cloning
On the favorable side with successful animal cloning - particularly cloning from an adult animal - you know exactly how your clone is going to turn out. This becomes especially useful when the whole intention behind cloning is to save a certain endangered species from becoming totally extinct.←for more info, please see http://www.buzzle.com/articles/cloning-extinct-animals.html

That this is possible was shown by cloning an Indian Gaur in 2001. The cloned Gaur, Noah, died of complications not related to the cloning procedure.

Speaking of saving extinct animals, I couldn’t help but think of Jurassic Park. Although in the movies looks like cloning extinct animals brings threat to humans, or maybe it truly would in reality, the idea of cloning them remains magically attractive to me. Especially, would the biodiversity allow, cloning those who became extinct because of our hunting.

What’s your idea?

Before I lead you off the topic, let’s go back and talk about Sexual reproduction, which differs from asexual reproduction, in that it involves fusion of cells (gametes←we knew in high school as配子), one derived form each parent, to form a zygote. The genetic processes involved in the production of gametes allow for some genetic changes in offspring.

The production of gametes is referred to as gametogenesis. This may be a complex process, involving sexual differentiation and the production of highly differentiated male and female gametes, or in lower eukaryotes identical cells may fuse–isogamy.

isogamy , in biology, a condition in which the sexual cells, or gametes, are of the same form and size and are usually indistinguishable from each other. Many algae and some fungi have isogamous gametes. In most sexual reproduction, as in mammals for example, the ovum is quite larger and of different appearance than the sperm cell. This condition is called anisogamy. (infoplease.com)

Whatever the biology of the process, one fact is obvious: gametogenesis must involve a halving of the chromosome number, otherwise each succeeding generation would have double the chromosome number of its parents.←That’s why, sexual reproduction is limited to species that are diploid or have a period of their life cycle in the diploid state.

Halving of chromosome numbers is achieved in a specialized form of cell division, meiosis(←we learned in high school as减数分裂), which is only observed in gametogenesis.

We will talk about meiosis more detailedly next section.

the blueprint of life [8]: eukaryotic structure of DNA 1(chromatin)

• Mitosis: 有丝分裂; Meiosis: 减数分裂

Interphase: 分裂间期; Prophase: 分裂前期; Metaphase: 分裂中期; Anaphase: 分裂后期; Telophase: 分裂末期

• Histone: 组蛋白 hhistidine 组氨酸

• Nucleosome: 核小体

•Chromosome: 染色体; Chromatin: 染色质; eu- 真染色质; hetero- 异染色质

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The total length of DNA in a eukaryotic cell depends on the species, but it can be thousands of times as much as in a prokaryotic genome.

Eukaryotic chromosome is made up of a number of discrete bodies called chromosomes. The DNA in each chromosome is believed to be a single linear molecule, which can be up to several centimeters long.

All these each contain a long linear DNA molecules, which must be packaged into the nucleus, a space of approximately the same volume as a bacterial cell

SO, much longer DNA chains packaged into a space of the same volume as a bacterial cell? → for example, 2 cm of DNA length versus ~10 µm of cell size for fruit fly; most condensed form of human chromosome is about ~2 µm long = 10,000× packing ratio

the obvious result is in their most highly condensed forms, the chromosomes have an enormously high DNA concentration: perhaps 200 mg/ml.!

The feat of packing is accomplished by the formation of a highly organized complex of DNA and protein, known as the chromatin, a nucleoprotein complex. (←our hero today, has finally showed up.)

Chromosomes greatly alter their level of compectness as cells progress through the cell cycle, vary between highly condensed chromosomes at metaphase(just before the cell division), and very much more diffuse structures in interphase.(This implies the existence of different levels of organization of chromatin)

More than 50% of the mass of chromatin is protein. Most of the protein in eukaryotic chromatin consists of histones, of which there are five families: H2A, H2B, H3 and H4, known as the core histones, and H1.

The core histones are small proteins, with masses between 10 and 20 kDa, and H1 histones are a little larger at around 23 kDa.

The unified atomic mass unit (symbol: u) or dalton (symbol: Da) is the standard unit that is used for indicating mass on an atomic or molecular scale (atomic mass). One dalton is approximately the mass of a nucleon and is equivalent to 1 g/mol.^[1] It is defined as one twelfth of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state,^[2] and has a value of 1.660538921(73)×10⁻²⁷ kg.^[3]

All histones proteins a large positive charge; between 20 and 30% of their sequences consist of the basic amino acids, lysine and arginine. This means that histones will bind very strongly to the negatively charged DNA in forming chromation.

amino acids in English?

Members of the same histone class(family) are very highly conserved between relatively unrelated species, for example between plants and animals, which testifies to their crucial role in the chromation.

Within a given species, there are normally a number of closely similar variants of a particular class, which may be expressed in different tissues, and at different stages in development.

There is not much similarity in sequence between the different histone classes, but structural studies have shown that the classes so share a similar tertiary structure, suggesting that all hisotnes are ultimately evolutionarily related.

H1 histones are somewhat distinct from the other histone classes in a number of ways; in addition to their larger size, there is more variation in H1 sequences both between and within species than in other classes. Histone H1 is more easily extracted from bulk chromatin, and seems to be present in roughly half the quantity of the other classes, of which there are very similar amounts.

Next section we will cover the distinct role of histone Hi in chromatin structure.