Mitosis and meiosis detail

Mitosis and Meiosis

idea;

You started off as a fertilized cell inside your mom, called a zygote. Now, you’re a thriving community of hundreds of millions of cells, all working together towards a common purpose: to keep you alive. How did so many cells come from just one?

Generally speaking, the answer is straightforward: many cells come from just one by repeated cell division. Your first form as a zygote split to make two cells. Then those cells split, making four...and so on and so forth, until you became the living, functioning organism you are today.

There are two ways cell division can happen in humans and most other animals, called mitosis and meiosis. When a cell divides by way of mitosis, it produces two clones of itself, each with the same number of chromosomes. When a cell divides by way of meiosis, it produces four cells, called gametes. Gametes are more commonly called sperm in males and eggs in females. Unlike in mitosis, the gametes produced by meiosis are not clones of the original cell, because each gamete has exactly half as many chromosomes as the original cell.

The concept of a chromosome

A chromosome is a thread-like object (scientists literally called them threads or loops when they were first discovered) made of a material called chromatin. Chromatin is made of DNA and special structural proteins called histones. One way to think of a chromosome is as one very long strand of DNA, with a bunch of histone proteins stuck to it like beads on a string.

Chromosomes are stored in the nuclei of cells. If you compare the diameter of a cell nucleus (between 2 and 10 microns) to the length of a chromosome (between 1 and 10 centimeters, when fully extended!), you can see that a chromosome must be scrunched up into a very small package in order to fit inside a nucleus. Actually, the average chromosome is about a thousand times longer than a cell nucleus is wide. The situation is a bit like how a very long snake can coil up into a tight ball.

The basic construction of chromosomes (made of chromatin) and structure (long but scrunched up) is the same in all animals. The difference is that each species has its own set number of chromosomes. For instance, all human cells (except gametes) have 46 chromosomes. Cells of nematodes (worms), other than gametes, have 4 chromosomes. The number of total chromosomes in the non-gamete cells of a particular species is called the diploid number for that species. The diploid number of humans is 46, and the diploid number of nematodes is 4.

The total number of chromosomes in the gametes of a particular species is referred to as the haploid number of that species. This number is always half of the diploid number. For instance, the haploid number in humans is 23, and the haploid number in nematodes is 2.

The concept of mitosis

The purpose of mitosis is to make more diploid cells. It works by copying each chromosome, and then separating the copies to different sides of the cell. That way, when the cell divides down the middle, each new cell gets its own copy of each chromosome.

The phases of mitosis

In the first step, called inter-phase, the DNA strand of a chromosome is copied (the DNA strand is replicated) and this copied strand is attached to the original strand at a spot called the centromere. This new structure is called a bivalent chromosome. A bivalent chromosome consists of two sister chromatids (DNA strands that are replicas of each other). When a chromosome exists as just one chromatid, just one DNA strand and its associated proteins, it is called a monovalent chromosome. Here is a drawing of what happens in a nematode nucleus (diploid number 4) during interphase, with individual chromatids represented as numbers, sister chromatids as the same number, and the centromere represented as a “-”.

The second and third steps of mitosis organize the newly created bivalent chromosomes so that they they can be split in an orderly fashion. A lot of care has to be taken with this process, because unequal splitting of chromosomes creates malfunctioning cells. Down syndrome is one disease that results from unequal splitting of chromosomes.

In the second step, pro-phase, the bivalent chromosomes condense into tight packages. Imagine the difference between a slinky fully stretched out, and a slinky that has been pressed back together. That's what happens to chromosomes during pro-phase: they get pressed together into tight packages.

In the third step of mitosis, called meta-phase, each chromosome lines up in a single file line at the center of the cell. By this point in time, the membrane enclosing the nucleus has dissolved, and mitotic spindles have attached themselves to each chromatids in all the chromosomes. Here is a diagram of what a nematode cell nucleus looks like after pro-phase and metaphase.

In the fourth step, ana-phase, the mitotic spindles pry each chromatid apart from its copy, and drag them to the opposite side of the cell. Four bivalent chromosomes become two groups of 4 monovalent chromosomes.

Once anaphase is over, the heavy lifting of mitosis is complete. In the final phase, telophase, membranes form around the two new groups of chromosomes, and the mitotic spindles that provided the power to create these groups are disassembled. Once mitosis is complete, the cell has two groups of 46 chromosomes, each enclosed with their own nuclear membrane. The cell then splits in two by a process called cytokinesis, creating two clones of the original cell, each with 46 monovalent chromosomes.

The concept of meiosis

The purpose of meiosis is to make haploid gametes. In order to explain the difference between mitosis and meiosis quickly and easily, consider the following analogy: You own a restaurant, and you keep 46 cookbooks on hand, to store all the recipes you need to make the food you sell. If you opened a new restaurant that you wanted to make the same food as the one that already exists, what would you do? Copy all 46 cookbooks, and take them to the new restaurant. That's like what happens in mitosis. Consider that the cookbooks are chromosomes, each containing lots of recipes that cells use to make “dishes,” called proteins. When cell division occurs, each cell wants to ensure that each new cell can make the same proteins as the original. So each of the chromosomes are copied and evenly distributed to both new cells—both cells get a copy of each “cookbook.”

Meiosis is different. Whereas as mitosis makes a new cell with the same number of chromosomes, meiosis is a reductive type of cell division: it results in cells with fewer chromosomes.

The phases of meiosis

Meiosis is split into two separate parts, called meiosis I and meiosis II.

Meiosis I starts with the copying of chromosomes and their condensation into compact forms (just like mitosis). The metaphase of meiosis I is different, though: Instead of lining up in single file, the bivalent chromosomes line up two-by-two. These groups, called homologous chromosomes, are what separate during the anaphase of meiosis I (compare this to the anaphase of mitosis, where chromatids separate).

If we look at the anaphase of meiosis I in nematodes (diploid number 4), the result is two groups of two bivalent chromosomes, rather than two groups of four monovalent ones. This difference in chromosome number in the post-anaphase groupings is really the only big difference between meiosis I and mitosis. Membranes form around the two groups, during telophase, and then the cell splits down the middle creating two non-clones. Each clone has half the number of chromosomes as the initial cell.

Meiosis II applies the process of mitosis to the two cells created by meiosis I. Since the chromosomes already exist in the bivalent form, interphase is skipped. The result is four cells, called gametes, each with two monovalent chromosomes.

Consider the following

What happens when cell division goes wrong?
Aneuploidy is a catchall term that refers to mistakes in the number of chromosomes in an organism (the prefix “eu-” essentially means “normal”, and adding “an-” in front --- “an-eu-” --- means “not normal”). For example, a human somatic cell with 46 chromosomes, or a nematode somatic cell with 4, or a human gamete with 23, is “eu-ploid” --- it has the right number of chromosomes. On the other hand, a human somatic cell with any other number of chromosomes --- 47, for instance --- is “an-eu-ploid” --- it has the wrong number of chromosomes.

One well-known medical condition that involves aneuploidy is Down syndrome. People born with Down syndrome have an extra copy of chromosome 21 --- instead of 2 homologous chromosomes, they have three. This mistake in chromosome number is called trisomy 21.

How trisomy 21 happens is a lot easier to explain than how it causes Down syndrome. During meiosis II, bivalent chromosomes are supposed to separate. Trisomy 21 is caused when this separation doesn’t occur. In humans, this means that one of the four gametes produced has the normal selection of 22 monovalent chromosomes, plus the bivalent version of chromosome 21. If this gamete is fertilized, a zygote is created with one extra chromosome.

This mistake has profound consequences. The physical and mental development of people with Down syndrome is curbed, and results in a spectrum of handicaps ranging in severity from mild to severe. But why? Clearly, having an extra set of the genes contained in chromosome 21 does something to development, but pinpointing the effects is very difficult. The puzzle of trisomy 21 is all the more vexing when you compare its effects with those of other, more benign aneuploidies. Women with so-called “triple X syndrome,” which occurs when a female’s somatic cells have three X chromosomes instead of two (for a total of 47 chromosomes), are, in most cases, visually and clinically indistinguishable from women without the “syndrome.” Similarly, men with “XYY syndrome” have an extra Y chromosome, but no distinguishable symptoms.

Clearly, the clinical significance of aneuploidy exists on a wide spectrum, from “no discernible effect” all the way to “profound mental and physical problems.” Unpacking the chain of genetic causality that creates this clinical spectrum still represents one of the frontiers of modern medicine.

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