<- table_of_contents|Table of Contents^start|Start^chapter_02|Chapter 02 -> Chapter 01. Mitosis and meiosis: a %%primer%% for genetics ===== Why you should care about meiosis ===== Meiosis is one of the most important and fundamental phenomena in all biology. All understanding of eukaryotic genetics must start with an understanding of meiosis, and all understanding of meiosis must start with an understanding of mitosis. Ironically, mitosis and meiosis are also among the topics that biology students are least interested in, and as a result they are also among the topics that students understand the least. These topics are sometimes challenging for students to learn because they are indeed complex; there are a lot of unfamiliar terms used to describe all the different steps of these processes; and students do not always connect the relevance of learning mitosis and meiosis with biology they can directly observe. Our goal in this chapter is to learn (or review) just enough about mitosis and meiosis to support our learning of genetics, and to minimize jargon where possible. To meet this goal, we will omit many of the important cell biology details. However, students are encouraged to study and review mitosis and meiosis from a cell biology perspective to gain a deeper understanding of cell division. You should also revisit this chapter when you get confused about concepts in later chapters that relate to meiosis. Finally, you should study [[appendix_a|Appendix A]], which goes into detail on the chromosome mechanics of meiosis using yeast as an example. ===== Understanding chromosomes ===== When thinking about mitosis and meiosis from the perspective of genetics, we really only care about how the chromosomes behave. In somatic cells (i.e., any cell that is not a reproductive cell), chromosomes usually exist as pairs. Human cells, for example, contain 23 pairs of chromosomes. Another way to say this is that human cells have 46 total chromosomes. In humans, these chromosome pairs are named by number, from largest to smallest (1 through 22), except for the sex chromosomes (the 23rd "pair"), which are named "X" and "Y". Each chromosome pair consists of two homologous chromosomes, each of which comes from the two different parents of the individual. For instance, each human somatic cell has two of Chromosome 1, two of Chromosome 2, two of Chromosome 3, etc. The mother contributes one of the chromosomes in the pair, and the father contributes the other. Homologous chromosomes are highly similar to each other but are not identical. The only exceptions are the sex chromosomes. Female humans have two X chromosomes that are homologous and pair with each other, but male humans have only one X chromosome; this X chromosome pairs with the much smaller Y (and not homologous) chromosome during meiosis. You probably already have at least a vague idea that chromosomes contain genes (an idea we will talk about more in [[chapter_04|Chapter 04]]) and genes control traits (or phenotypes), and since two parents are different people with different traits, it follows that their chromosomes are not identical to each other. On the other hand, all humans have similar traits; that is, different individual humans are still very similar to each other (we all have the same general anatomy, our physiology generally works in the same way, etc). Therefore, it should also be pretty easy to imagine that even though homologous chromosomes from two parents are not identical, they must be very similar to each other. ===== Mitosis results in two genetically identical daughter cells ===== At the beginning of the 20th century, microscopes allowed scientists to watch chromosomes in the nuclei (singular: nucleus) of dividing somatic cells. The process of somatic cells dividing is called mitosis (Fig. {{ref>Fig1}}).

{{ :mitosis.jpg?400 |}} A conceptual diagram of mitosis of a human cell. Although humans have 46 chromosomes, this diagram only shows 4 chromosomes that comprise two homologous pairs to make the diagram less complicated. You can identify the pairs based on their size. The teal and red chromosomes are one pair, and the green and blue chromosomes are another pair. Source: [[https://www.genome.gov/genetics-glossary/Mitosis|National Human Genome Research Institute]]. Licensing: public domain.

From a genetics perspective, the goal of mitosis is to distribute replicas of each chromosome into two newly formed daughter cells, so that each daughter cell has the exact same chromosomal content as the parent cell. In other words, each daughter cell is a genetic clone of the parent cell. Prior to mitosis (in a stage of the cell cycle called interphase), cells will replicate their chromosomes; each chromosome becomes doubled, and we now call this replicated pair of chromosomes sister chromatids (in Fig. {{ref>Fig1}}, these duplicated sister chromatids are labeled as "duplicated chromatin"). Unlike homologous chromosomes, sister chromatids are almost always identical to each other. After chromosomes replicate, there should be a total of two chromatids per chromosome, and four chromatids per homologous chromosome pair. For example, after chromosome replication there should be a total of four chromatids representing Chromosome 1; two sister chromatids that are identical to each other that represent the maternal contribution, and two sister chromatids (also identical to each other and similar but different from the first two) representing the paternal contribution. The two identical sister chromatids are held together by a protein called cohesin, which resembles a rubber band that holds the two sister chromatids together. The homologous chromosomes do not associate with each other. The stages of mitosis may be familiar to you if you've learned about mitosis or the cell cycle before. They are summarized in the order in which they occur as follows: - Prophase: The chromatin of the chromosomes condense to form the familiar bar-shaped structures you may be familiar with, and the mitotic spindle (sometimes just called the spindle) starts to form; - Prometaphase: the nuclear membrane disassembles, and spindle fibers attach to a structure on the chromosomes called the centromere; - Metaphase: Chromosomes (joined sister chromatid pairs) are positioned in the middle of the cell by the spindle; - Anaphase: Sister chromatids are pulled apart by the spindle and move toward the two centrosomes; - Telophase and cytokinesis: Nuclei reform and the cell membrane pinches to form two new daughter cells. In TNBGGA, we almost never care about the details of the cell biology. Therefore, we will not worry about the nucleus past this point, and we will not be concerned with how the spindle works, either, except to generally understand that the spindle is a rope-like structure that attaches to centromeres and pulls chromosomes apart during cell division. Most drawings in TNBGGA will omit the nucleus and simplify the spindle to make it easier to focus just on what the chromosomes are doing. However, serious students of biology will want to understand mitosis from various perspectives. For instance, thinking about mitosis through the lens of genetics helps you understand how chromosomes move around and is therefore helpful in thinking about how genetic diseases might be inherited. But thinking about mitosis through the lens of cell biology will help you understand different aspects of cancer biology and how cancer biologists think of ways to treat cancer. ===== Meiosis results in four non-identical daughter cells called gametes ===== Cells that divide to form germ cells (also called gametes) such as oocytes (eggs) or sperm undergo a very different kind of cell division called meiosis (Fig. {{ref>Fig2}}). Similar to mitosis, chromosome replication happens before meiosis during interphase. The pair of sister chromatids are also held together after replication, and that structure is sometimes referred to as a dyad. However, meiosis differs from mitosis in two fundamental ways: - In meiosis, there are two rounds of chromosome segregation and cell division for every one round of chromosome replication. These two rounds are called meiosis I and meiosis II. In each round, the cell goes through the same steps as mitosis; meiosis I includes prophase I, prometaphase I, etc., and meiosis II includes prophase II, prometaphase II, etc. This means that at the end of meiosis there are four daughter cells produced, whereas there are only two daughter cells produced after mitosis. In addition, it means that each gamete receives only one of the two homologous chromosomes in a pair. - During prophase I, the dyads pair with one another. This structure where four chromatids are all paired together has a few different names. In cell biology, it is called the synaptonemal complex, and the process of forming this structure is called synapsis. In genetics, we usually refer to this structure instead as the tetrad, and this is the term we will use in this book. Essentially, it is the tetrads that are lined up in the middle of the cell during metaphase I. In anaphase I, the dyads separate from each other. The sister chromatids separate during the second meiotic division during anaphase II. This difference in alignment is probably the most important thing to know when comparing mitosis and meiosis.

{{ :meiosis.jpg?400 |}} A conceptual diagram of meiosis of a human cell. Like Fig. 1.1, this diagram only shows 4 chromosomes that comprise two homologous pairs that can be distinguished based on their size. The color coding is a little different to emphasize the maternal and paternal contributions; teal (maternal) and blue (paternal) represent one pair, and orange (maternal) and red (paternal) represent another pair. Compare how the chromosomes line up in metaphase of mitosis in Fig. 1.1 vs metaphase I in this figure. This figure also illustrates an important concept called crossing over, which we will discuss in Chapter 5. Note that the daughter cells of the first division are labeled as 2n; this is in error (see also footnote in this chapter). Source: [[https://www.genome.gov/genetics-glossary/Meiosis|National Human Genome Research Institute]]. Licensing: public domain.

At the end of meiosis, there is half as much chromosomal content in the four daughter cells compared to the mother cell. Generally speaking, we say that the mother cell is diploid; the two daughter cells at the end of mitosis are also diploid; and the four daughter cells at the end of meiosis are haploid ((In some textbooks, the two daughter cells after meiosis I are also referred to as haploid, despite the fact that these cells have "2n" DNA content. While this is classically considered "correct", it is also a very old-fashioned way of thinking and is needlessly confusing. We get around this problem in this book by not calling the meiosis I daughter cells anything - they are only transient products of meiosis and are not that important anyway. )). The terms diploid and haploid refer to the number of copies of genetic information that are contained in the cell. The etymology (origin of these words) is Greek - "haplo" meaning single, "diplo" meaning double, and "ploidy" meaning "likeness". A diploid somatic cell contains two copies of genetic information, but a haploid gamete contains just one copy. In fact, the word meiosis also comes from a Greek word that means "lessening" - it is a process that decreases the amount of genetic information in a cell. Geneticists use the symbols "1n" to indicate haploid and "2n" to indicate diploid. In humans, we would say that n=23; the value for "n" tells you how many pairs of homologous chromosomes there are. There are two other important features of meiosis: - In prophase I when the tetrad is forming, non-sister chromatids can exchange portions of their material with each other. This is called crossing over. We will ignore this for now but this is very important; more on this in Chapter 5. - In metaphase I when the tetrads are lined up in the middle of the cell, the orientation of the tetrad is random. Each dyad has an equal chance of facing one side of the spindle as the other. A final word about gametes and somatic cells: The process of sexual reproduction occurs when haploid gametes from opposite sexes fuse. This results in a new somatic cell (called the zygote) that is now diploid. This zygote can undergo mitosis. In some cases such as with yeast, gametes can undergo mitosis to produce additional haploid daughter cells, but in most examples in this book this does not happen - in general, gametes do not further divide. Meiosis is worth revisiting often as we explore genetics in subsequent chapters. Also, be careful of confusing prokaryotes (bacteria) with eukaryotes - only eukaryotes go through mitosis and meiosis, whereas bacteria divide by binary fission, which is a different type of cell division. It is strongly recommended that the serious student at this point study [[appendix_a|Appendix A]], which goes into a deep dive on the details of the chromosome mechanics of meiosis. A final closing note: there is a lot of jargon (specialized vocabulary) associated with mitosis and meiosis. While you can't avoid memorizing and learning these new terms, don't make that your main focus. The most important part of learning about mitosis and meiosis is understanding how the chromosomes move. It's much better to know how chromosomes move and be unsure about the terms, rather than the other way around. ===== Questions and exercises ===== Exercise 1: After reading this chapter and thinking about it, get some colored pens and some paper. Try to draw mitosis of a diploid cell that has two pairs of chromosomes (n=2). Focus just on the replication and movement of chromosomes. Don't just copy it from Figure {{ref>Fig1}} - try to draw it based on your understanding of what the end goal is of mitosis and how you think it works. In your drawing, make sure there is an easy way to distinguish between different chromosomes (by using different sizes, colors, etc.). After you complete your drawing, compare it to the illustration here - how close were you? Note where you made mistakes and try again from scratch. Keep at it until you can get it perfect. Exercise 2: Repeat Exercise 1 except with meiosis.