Lesson Five Chromosomes in Meiosis, Medicine and Evolution by Dr Jamie Love 2002 - 2010

In this lesson we will go a little deeper into the details of meiosis and chromosomes. I will reiterate some information you learned in the last lesson but will do so in a different light. I like to use topics from medicine and evolution but I do not expect you to memorize details. In this lesson try to focus on the mechanisms of chromosome interaction, structure, evolution and disorders - but not the specifics.

Of course the purpose of meiosis is to create gametes and they must be haploid so as to create a diploid zygote when fused with another gamete.
You should also understand that the independent direction in which the tetrad breaks up (in meiosis I) leads to a wide variety of possible gametes and that number increases with the increasing number of chromosomes. Of course, each species has a set number of chromosomes so what I am talking about here is a comparison between different species.

Here is a good opportunity to review and use what you have learned. As you read the three sections below be sure you understand why I come to each conclusion or answer. It might help to draw these chromosomes to better understand how they migrate and divide during meiosis (I and II).

1. Consider an organism with only one pair of homologous chromosomes. It has a haploid number of 1 and a diploid number of 2 because its n = 1.

An organism with only one homologous pair of chromosomes can only produce two types of gametes - one carrying the #1P and the other carrying the #1M.

2. An organism with two pairs of homologous chromosomes has a haploid number of 2 and a diploid number of 4 because its n = 2.

An organism with two homologous pairs (of chromosomes) can produce four types of gametes. These would be (carrying) :

1. #1P and #2P
2. #1P and #2M
3. #1M and #2P
4. #1M and #2M

Notice that each gamete MUST have one of EACH chromosome NUMBER. That is, each gamete in this example has a #1 and #2 chromosome. The only variation is in the combinations (M or P) of #1 and #2 it received. It is impossible (actually "faulty", an error) to create gametes containing combinations like #1P and #1M or #2P and #2M.

3. You have 23 pairs of homologous chromosomes so you have a haploid number of 23 and a diploid number of 46 because your n = 23. [Notice that n always equals the number of chromosomes in a gamete and 2n is the number of chromosomes in other cells in interphase.]
Your 23 homologous pairs (of chromosomes) can produce millions of different types of gametes because of all the possible combinations.

Here's a possible pattern in one single gamete for a human.
#1M, #2P, #3P, #4P, #5P, #6P, #7P, #8P, #9P, and so on to the last chromosome, #23P.
Notice that only the first chromosome (#1) was maternal and I assumed all the rest are paternal.
There would be an "opposite" gamete that read …
#1P, #2M, #3M, #4M, #5M, #6M, #7M, #8M #9M, and so on to the last chromosome, #23M.
That is just one pair and they are both produced in the same meiosis, but don't bother working out how. The important point is that we could have had ANY combination as long as we ended up with one chromosome from each homologous pair (one #1, one #2, one #3, etc.) in each gamete.

As I said earlier, an organism with 23 homologous pairs can produce over four million different gametes due to the random "assignment" of the maternal and paternal pairs to each pole during anaphase I.

But that's not all!

Recall that I mentioned some "swapping" goes on during prophase I and I promised we'd come back to it. Now is a good time.

Prophase I is actually a very long phase. By the time chromosomes become visible in late prophase I they are already paired up as tetrads and tangled together. Each M and P lie parallel to each other with their arms (chromatids) entwined in a process called synapsis. ["Syn" is Greek for "together".]

Synapsis is worth understanding because it explains the tetrads and the events that follow. We don't know exactly how homologous pairs find each other although it definitely has something to do with their shared DNA patterns. Regardless, synapsis is a highly specific and organized alignment of the homologous chromosomes causing their genes, the specific DNA segments, to line up. Apparently this close association of similar DNA sequences causes the chromatid arms to mix and mingle. Their DNA stands actually break and they swap bits of DNA between them! This exchange of genetic material is called crossing over and it produces new combinations of genetic material along both chromosomes. The chromatids involved in crossing over will have the same ORDER of genetic materials but the swapping may have introduced some new TYPES of genetic materials.

Crossing over is not really seen under the microscope, but it is inferred from the patterns of crossed over chromatids locked together at prophase I.

These regions are called chiasmata (meaning "cross" in Greek). Chiasma is the singular form. There are usually many chiasmata along the length of a pair and many crossing over events occur among all four chromatids in the pair of homologous chromosomes. After several crossing over events it becomes difficult to say which is the maternal and which is the paternal. Don't worry about that because I won't require you to tell me. However, if you remembered that the centromere defines the chromosome you'd be able to make a good guess as to how we define the maternal and paternal chromosomes in spite of the complications of crossing over. Each chiasma represents a crossing over event and causes recombination along that part of the chromatids undergoing the exchange.

These chiasmata are also important in creating the tetrad pairs along the metaphase I plate. Earlier I skipped over the kinetochores and other particulars during prophase I. Now is a good time to point out that chromosomes in prophase I have only ONE kinetochore at the centromere - not two as in prophase of mitosis.

You may be wondering how tetrads can be pulled back and forth if both chromosomes have only one kinetochore. The chiasmata provide the answer! Notice that a chiasma will "link" the dyads into tetrads. When a pair of chromatids become tangled in chiasmata they effectively lock the two chromosomes (dyads) together into a tetrad.

Now each chromosome's kinetochore can play "tug-of-war" like before as they work towards a "draw" at metaphase I.

You may be wondering "Why all the fuss?"
Well, it's very important to understand chromosome movement and structure. Let's take some time discussing how chromosomes are of importance to two areas of biology - medicine and evolution.

Human gametes should have 23 chromosomes - one for each chromosome (#1, #2, #3, etc.). If something went wrong in anaphase I or anaphase II of meiosis the resulting gametes would not have the correct number of chromosomes. One gamete may get 22 chromosomes and the other would get 24 chromosomes. Imagine the fusion of either of those "bad" gametes with a healthy gamete. The zygote created would have either 47 or 45 chromosomes, not the normal complement of 46 chromosomes.

You will recall when the number of chromosomes in a cell is "off" by one or a few, we call that condition aneuploidy.

Most human aneuploidies are fatal. For example, a zygote with three #1's or only one #1 would fail to develop. That's because there are a lot of important genes on chromosome #1 and you must have the proper amount of them to survive. On the other hand people can survive with too many or too few of the sex chromosomes. (The sex chromosomes are the 23rd pair.) We haven't talked about the sex chromosomes yet, but we will in a future lesson so I'd like to leave their discussion for later. Other than sex chromosomes, there is only one human aneuploidy that you are likely to meet - Down syndrome.

Down syndrome is also called "trisomy 21" because people with Down syndrome have an extra copy of chromosome #21.
[That means they have a total of 47 chromosomes. Right? And that is not the normal complement of 46 chromosomes, so Down syndrome is an aneuploidy. Right?]
Human chromosome #21 is one of the smallest chromosomes and apparently life goes on if there is an "overdose" of those few genes.
Down syndrome is the single most common genetic cause of moderate mental retardation. Patients with Down syndrome have several distinguishing features of the face and hands and they have a high incident of congenital ("born with") heart disease and abnormalities of the digestive system. They also have a higher incidence of leukemia. About one child in 800 is born with Down syndrome and the chances of having a Down syndrome baby increase with the mother's age. Although people with Down syndrome have a lower life expectancy and lower IQ, they do not require hospital care - although each individual may have specific educational and medical needs that must be addressed. [Don't bother memorizing this information about Down syndrome. I'm providing it as an example of aneuploidy and it’s the idea of aneuploidy that I want you to understand. But some folks want to know a little more and that is why I've provided this information. ]

Sometimes a gamete has the correct number of chromosomes but one of them is damaged, perhaps missing a piece of genetic material. There are several human genetic diseases caused by "broken chromosomes" but fortunately they are rare. The chromosome is usually broken at some stage before meiosis and the damaged chromosome passes through meiosis as if they were perfectly normal. Zygotes produced from such chromosomes are deficient in genetic materials and that often causes severe problems.

For example, babies born with a missing piece of chromosome #5 have a syndrome called Cri du Chat (French for "cry of the cat") because their crying sounds like a meowing cat. Crying is the least of their worries. These unfortunate babies have a variety of serious medical problems most dramatic of which is a small brain and severe mental retardation. [Again, don't memorize these medical conditions. It's just to illustrate an example.]

Cytogeneticists, people who study chromosomes, have developed a very precise way to identify and name specific parts of each chromosome. For example, the piece of chromosome #5 missing in Cri du Chat syndrome extends from the top of that chromosome, its short arm, to a specific position called 5p15.

Cytogeneticists arrange chromosomes from the largest (number one, or #1) to the smallest (number twenty-two, or #22, in the case of humans) - not counting the two sex chromosomes (which we will talk about in subsequent lessons). So, you would be correct to guess that chromosome number 5 (#5) is the fifth largest chromosome.

After arranging chromosomes by size, cytogeneticists orient them so the smaller part of the chromosome is pointing up. Of course, this orientation really depends upon the position of the centromere along the length of the chromosome. Regardless, the "short" portion (smaller arm) is given the designation "p" and the "long" portion (long arm) is labeled "q". Do NOT confuse this with the P and M of paternal and maternal! (Watch your p's and q's. ) Cytogeneticists also stain the chromosomes, via a technique I do not want to get into, that produces a banding pattern. These bands are spread unevenly but consistently along the length of each chromosome allowing us to more easily identify them as well as to identify specific portions of each chromosome. Of course, homologs looks identical - they have the same banding pattern.

Indeed, the "standard" X-shaped chromosomes will show identical banding of each sister chromatid because sister chromatids are identical to each other. Therefore, in order to make the mapping and naming simple, cytogeneticists often display the chromosome as a single chromatid, as if it has undergone anaphase, like I have shown in my drawing above on the right.

We will not go into it details of how the position numbers are assigned (but you might notice the progression of the numbers increases moving from the centromere and they correspond to the banding). By looking at the map of chromosome 5 (above), I think you will now understand that Cri du Chat syndrome occurs when there is a break at position #5p15. That tiny tip drifts away and important genetic information, coded from #5p15 to the telomere, is lost.

The position on a chromosome is called a locus. Genetic information is contained at each locus. Of course, you have two chromosomes in a diploid cell so that locus will be found twice in each diploid cell. And, if the cell has progressed past the S phase there will actually be four copies of that locus. BUT (and this is an important "but") all four of them are still the same locus! Each set of chromosomes has one and only one #5p15 and we always refer to that as a single position even though there may be several copies or variations of it.

This is important to understand so let's walk through it again. Each gene, bit of genetic information, has a position - a locus. At a different locus in the set, say on a different chromosome (#4) or a different position (#5p13), there will be different genetic information. Two genes cannot share the same locus. Different genes reside at different loci (the plural of locus). Imagine loci as page numbers in a book. You may have four copies of that identical book but in page 515 of each book you will find the same information. At a different page, say page 513, you will find information different from that on page 515. Regardless, the information at page 153 will be the same as on page 153 of every book.

In point of fact, there might be slight variations among the details but I do not want to get too far ahead of ourselves. We will return to this idea of locus and loci in subsequent lessons but it is important to introduce the definitions at this point.

As I mentioned - long ago, it seems - cancerous cells have a variety of chromosomal abnormalities including broken and rearranged chromosomes. Generally speaking, the more unusual the chromosomal make up of a cancer cell the more aggressive (deadly) it is. The chromosomes of cancerous cells are studied and specific loci (positions) of breaks and other mutations are noted. This kind of information can tell us a great deal about cell biology so may be helpful in diagnosing the cancer and, thus, allow for better treatment of the patient.
[You will also recall that cancerous cells often has various amounts of aneuploidy - extra and lost chromosomes. Cancer cells have very complicated genetics that gives rise to their very complicated biology.]

However, chromosome abnormalities are not all about disease.
They are important in evolution, too.

Plant evolution has benefited greatly from polyploidy. You will recall that polyploidy is when the organism has extra sets of chromosomes so its cells have 3n, or 4n, or 5n, etc. Note that this is different from aneuploidy. In aneuploidy there is only a slight difference in the chromosome counts but in polyploidy the chromosomes are increased in exact units of "n".

Primula verticillata and Primula florbunda are two species of primrose and they both have 18 chromosomes each. [So n = 9 and 2n = 18.] All their "normal" cells contain 18 chromosomes (2n) and their gametes contain 9 chromosomes (n). [Don't memorize these details but use them to understand what I am about to explain about polyploidy and how it helps evolution.] By crossing them you can produce a hybrid plant that also has 18 chromosomes (2n) but these hybrid Primula are infertile. Most hybrids are infertile. The mule, a cross between a horse and an ass, is a good example of an infertile hybrid. However, you can "force" a plant through its sterility by adding a chemical called colchicine. Colchicine disrupts nuclear division by inhibiting the formation of spindle fibers. The gametes produced after treatment with colchicine have 18 chromosomes - they are 2n! When these gametes are fused they create a zygote with 36 chromosomes - 4n! That is a polyploid zygote. (A tertaploid, to be exact.) Experiments like these produced a new species called Primula kewensis with a 2n = 36 and n = 18. It cannot breed with either of its parent species, Primula verticillata or Primula florbunda, but it's very capable of producing healthy offspring from its own (2n = 36) kind.

Many families of wild flowers are composed of species that consist of simple multiples of a basic number of chromosomes - the basic number being "n". By looking at the number of chromosomes in groups of related species it is possible to guess which originated from polyploid hybridization. [There are natural agents in the environment that will produce polyploids by interfering with meiosis. As a matter of fact, colchicine is extracted from some species of plants!]

It is estimated that 70-80% of angiosperms (plants with hard seeds) are the product of natural polyploid evolution.

Polyploidy is common among plants but most animals cannot tolerate such an imbalance. One interesting exception is among a group of lizards called "racerunners" - genus Cnemidophorus (pronounced "Nem-ee-dof-or-us"). Some species of these lizards, known as "Cnemies" to folks who study them, are a triploid (3n) species! Careful analysis of their chromosomes show that their genome is composed of 2n from one species of Cnemidophorus and an extra 1n from another related species of Cnemidophorus. Chances are that these "Cnemies" are the offspring of a hybridization between two separate species of Cnemidophorus - one of which accidentally produced a diploid gamete! When that diploid gamete was fertilized with the haploid gamete of the other species the resulting zygote was triploid.

You might wonder how a triploid species would undergo meiosis. Think about it. What would the metaphase plate look like during metaphase I? Would it have tetrads? Maybe "hexads" (pairs of three)? Confusing isn't it? Well, we do not know what the metaphase I looks like in these triploid species of Cnemidophorus because they do NOT undergo meiosis at all. Nor do they undergo fertilization. So, do they just die off and go extinct. No, they reproduce by mitosis! They lay eggs containing a "premade" zygote that is 100% genetically identical to its triploid mother! This method of reproduction is called parthenogenesis (meaning "virgin origins"). These polyploid lizards are an all female "species" - producing clones of themselves! (Males trying to clone themselves just cannot do it - you have to make an egg to reproduce.) We are not quite sure how or why polyploid lizards can clone themselves nor why these polyploids are found only among hybridized Cnemidophorus.
Regardless, this is a natural-cloning species, long before Dolly. These strange lizards inhabit various parts of the southwestern USA and parts of Central America.

In case you are wondering - polyploidy is fatal for humans and all other mammals.

Chromosomes can be involved in evolution in another way. Earlier I told you how broken or rearranged chromosomes can cause an imbalance and cause disease in humans. Sometimes those rearrangements are not fatal and they might even be helpful in creating a new species!

Let's consider the chromosomes of humans and the other great apes of Africa. As you know, we have 2n = 46. Chimpanzees and gorillas have 48 chromosomes.
If you are surprised to learn that chimps and gorillas have more chromosomes than a human, you should understand that there are many species with many more chromosomes than us. The total number of chromosomes in a species is no indication of its "advancement". And, as you shall see, funny things happen in chromosome evolution.
Chimps and gorillas have two extra pairs of chromosomes, so they should have 2n = 50, BUT they do not have human chromosome pair #2, so they really have 2n = 48.
That may be difficult to imagine, especially with all this talk of diploid cells so let's look at the situation with respect to the gametes. Human gametes have 23 chromosomes but chimp and gorilla gametes have 24 chromosomes.

Chimps and gorillas have two rather unremarkable chromosomes that are not found in humans. Both of these chromosomes are more V-shaped than X-shaped. Let's call them #2p and #2q. (You will see why - or maybe you have already guessed.) Careful analysis of the chromosomes shows that the human #2 was actually produced by the fusion of those two chromosomes! [This particular type of fusion, where two V-shaped chromosomes fuse into one X-shaped chromosome, is common in evolution. We call it a "Robertsonian fusion", but you don’t have to know that.]

By the way, it would be wrong to conclude that this fusion caused humans to have the special traits that make us different from chimps or gorillas. Those differences are probably caused by small differences in the DNA sequences. These chromosomal rearrangements are really just markers of chromosome evolution but they may also have produced a reproductive barrier that made it impossible for our ancestors to mate with the ancestors of chimps and gorillas.

Reproductive barriers are an important part of evolution because they cause divergence of the genetic population into separate breeding pools.

Imagine that early "prehuman" with its fused #2p-#2q. It would produce gametes that contain 23 chromosomes (like ours) but it would be living in a world in which all the other apes were making gametes containing 24 chromosomes. When this "prehuman" mated with its neighbors the offspring would have a "2n" equal to 47. (No that is NOT Down syndrome! Nothing like it.) Most importantly, that individual with 47 chromosomes, even if it lived a good and healthy life, would have great difficulty making gametes. (Again, think about that metaphase I plate.) Indeed, its only hope of reproduction would be to mate with an individual with the same (weird, new) chromosomal set. And where would s/he find that special mate?
Well, it is effectively "impossible" to hope that a new but identical chromosomal fusion would occur again during a lifetime. Instead it is likely that the original parent that produced the original fused #2 chromosome did so some time during it embryogenesis (before it was born) and some, most or all of the cells in its body contained the fused #2. That means its gametes would carry the new #2. (Actually, only half his gametes would carry the fused #2 but that doesn't really change our story.) That means he would have offspring containing his new #2. The answer to our puzzle is the striking conclusion that very high levels of inbreeding occurred in our ancient ancestry! The original #2 primate mated with his (or her) offspring or the offspring mated among themselves! And we all carry that #2 as proof that the inbreeding relationship occured in our direct ancestor.

We've covered a lot of information in this lesson. You should now have a very detailed understanding of chromosomes and the nuclear divisions (mitosis, meiosis I and meiosis II). Check your Study Guide with the Completed (Teacher's) version and then discover how much you really know with the SAQs.

This work was created by Dr Jamie Love and licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.