DNA is deoxyribonucleic acid. It is made up of four chemical bases: adenine, guanine, cytosine, and thymine. Each base has an attached sugar molecule and phosphate molecule, and this combination is called a nucleotide. The bases form pairs, with adenine pairing up with thymine and cytosine pairing up with guanine. The nucleotides form long paired chains that twist into a double helix with the bases in the middle and the sugar and phosphate molecules on the sides in a ladder structure. This is the DNA molecule, which is primarily found in the cell nucleus, although there is a little DNA in the mitochondria.
The DNA molecule coils around histone proteins and this structure is called a chromosome. The histones help chromosomes hold their shape. Each chromosome has two parts, called arms, separated by a narrow spot called the centromere. The arms are unequal lengths, with the short arm labeled the “p” arm and the long arm labeled the “q” arm. Genes are sequences of nucleotides in a DNA molecule ranging in length from several hundred to millions. A gene acts as a template for making a protein. Genes can have small variations in the sequence of bases. These variants are called alleles.
Understanding the base pairs and nucleotide chains explains the primary structure of DNA, and understanding the double helix explains the secondary structure, but it is important to consider that DNA does not exist as long, relaxed chains. Wrapped around the histones, the chromosomes have a tertiary structure which can bring together sections of DNA that are distant from each other in the nucleotide chain. The interactions of these different areas produce effects that cannot be predicted from just the secondary structure. There is also a mechanism that determines which genes are active at any particular time. Genes can be turned on and off by the process called methylation during which methyl groups attach to sections of DNA. Methylation modifies gene expression without changing the DNA and this process is called epigenetic modification. Epigenetics increases the adaptability of genes by making it possible to change the phenotype without altering the genotype.
There are two types of DNA replication. In the first type, mitosis, DNA is replicated as a cell replicates itself. Cells are replicated during the growth of an organism and as part of a cycle of replacement in a mature organism. Each new cell contains an exact copy of the parent cell DNA. Mitosis has five phases. Before mitosis begins, during the stage called interphase, the chromosomes replicate themselves. The new strand remains attached to the original strand at the centromere, and the two strands are called sister chromatids. In the first stage of mitosis, prophase, the chromosomes condense and a structure called the mitotic spindle begins to form outside the nuclear envelope. The mitotic spindle is made up of microtubules and proteins, and has poles at opposite ends of the nucleus. The next stage, prometaphase, begins with the breakdown of the nuclear envelope. The parts of the mitotic spindle move in and attach to centrioles in the centromeres of the chromosomes.
The mitotic spindle is essential for keeping the chromosomes organized during cell division and making sure that the new cells have the right number of chromosomes. If, as sometimes happens, a new cell ends up with the wrong number of chromosomes, it is called aneuploidy. When aneuploidy occurs during mitosis, it can cause cancer. During metaphase, the next stage, the chromosomes are all lined up by the pull of the spindle microtubules. Once they are lined up, prophase begins with the separation of the sister chromatids. Each chromatid is pulled toward the opposite pole. In the final phase, telophase, the chromatids fully separate and new nuclear envelopes form around the two groups of chromosomes. Finally, the cell finishes dividing in a process called cytokinesis, producing two cells, each with the same DNA content as the parent cell.
The second type of DNA replication is called meiosis, which creates the germ cells used for reproduction. If aneuploidy occurs during meiosis, it usually causes a miscarriage, otherwise it can cause birth defects such as Down Syndrome, which is usually the result of having three copies of chromosome 21 instead of two. There are two cell divisions in meiosis and the resulting germ cells contain half the DNA of the original cell. Meiosis starts the same way as mitosis, with the formation of sister chromatids. But in meiosis, the first step is the pairing of the chromosome homologues. The mitotic spindle separates the homologue pairs instead of the sister chromatids. Cytokinesis then results in two cells, each with the sister chromatids of one homologue. Since the sister chromatids already exist, there is no DNA replication before the next cell division takes place. Another spindle forms and this time the sister chromatids are pulled apart to opposite poles. Nuclear envelopes form and cytokinesis produces four cells, each with one homologue for each chromosome.
Comparing the two types of replication, the process of mitosis produces two identical cells from the original cell, while meiosis produces four cells from the original cell, each containing half the amount of DNA of the parent cell, with half of the chromosomes from the maternal source and half from the paternal source. The chromosomes are randomly assorted, so the four cells may share anywhere from 0% to 100% of their genes, with an average of 50%. This means that theoretically two siblings could have no genes in common. In reality, mitochondrial DNA in the maternal germ cell is transmitted to all the offspring, so there will always be a few genes in common.
Meiosis and Genetic Variation
Meiosis is an important source of genetic variation. It contributes to genetic variation by producing the germ cells, which will be fertilized by germ cells from other organisms, resulting in a cell with a new combination of maternal and paternal chromosomes. It also allows the reassortment of chromosomes, so that the parent chromosomes do not have to be reproduced as a set. When the second, final, cell division occurs, the homologues move to the poles independently of each other, so the germ cells contain random combinations of the paternal and maternal chromosomes. This explains why offspring have a combination of parental traits, and this constant mixing creates the variation needed for natural selection. Another way meiosis provides variation is when the homologues pair up and genetic recombination occurs through the process of crossing-over.
This occurs when a piece of a chromatid breaks off and attaches to the non-sister chromatid. Instead of reassorting whole chromosomes, this reassorts parts of chromosomes, creating new combinations of genes within a chromosome. Crossing-over is a riskier source of variation though, because if the exchanged pieces are not the same length and do not contain the same genes, one germ cell could end up with less DNA and another germ cell could end up with more DNA than the parent cell. These germ cells with different amounts of DNA may not result in viable offspring, or can cause birth defects. When this happens with chromosome 21 it can be another cause of Down Syndrome.
Replication of DNA is an important component of cell reproduction and germ cell production. Variation is not desirable during mitosis and there are a number of mechanisms to prevent it and to discard cells that do not have a faithful copy of the parent cell DNA. Variation is balanced with checks during meiosis in an attempt to provide the variation a species needs in order to be able to adapt to a changing environment while maintaining enough order to produce viable germ cells.