Mini-review of Chromosomal Structure and Organization
Note: It is assumed that you have a basic background in genetics and the cell cycle from previous biology courses that you have taken. You need to be familiar with the words shown in bold in this section. If you are unfamiliar with those terms, you should refer to a biology text for further information and diagrams.
In eukaryotic organisms, DNA is present in structures called chromosomes. Each chromosome consists of a single two-stranded DNA molecule. Genes are located along the chromosomes and the position at which a particular gene is found is called a locus (plural: loci). In diploid organisms, each cell contains two sets of chromosomes. (Do not confuse this with the two strands of DNA within a single chromosome.) The two versions of each kind of chromosome are called homologous chromosomes. This means that along their length both homologues have the same loci arranged in the same order. For example, humans have 23 kinds of chromosomes (Fig. 12). This is represented by "N=23". Since two versions of each kind of chromosome are present, there are a total of 46 chromosomes in human cells (i.e. 2N=46).
Fig. 12. Karyotype of a human female. Note that two of each kind of chromosome is present. The correspondence of the stain banding patterns indicates that the members of the pairs are homologues.
In normal cell division (mitosis), each of the chromosomes replicates before the cell divides. Each of the two daughter cells gets one copy of each chromosome. Thus each daughter cell is an exact duplicate of the parent. For example, in humans, each daughter cell has the same 46 chromosomes as its parent cell. During the formation of gametes (eggs and sperm), a special type of cell division (meiosis) occurs. The complete process of meiosis is complex, but the end result is that each daughter cell (which will ultimately become a gamete) receives at random one of the two homologous chromosomes of each kind that is present in the species. Therefore, in humans, gametes have 23 chromosomes. When the gametes combine (fertilization), the resulting zygote has pairs of homologous chromosomes, with one of each kind of chromosome coming from each of the parents. In humans, one copy of chromosomes 1 through 22 and an X chromosome comes from the mother, and one copy of chromosomes 1 through 22 and an X or Y chromosome comes from the father. The X and Y chromosomes are not homologous but function as a 23rd pair in male offspring.
Fig. 13 Chromosomes, loci, and alleles in a diploid organism
Since each member of a homologous pair of chromosomes has the same series of loci along its length, an individual organism can have as many as two different versions of the DNA sequence at any locus. A version of a sequence is called an allele (Fig. 13). In classic Mendelian genetics, alleles at a locus are represented by one or more letters, such as "T" or "t", "F" and "S", "Xa" and "XA", etc. If the locus is part of a protein-coding sequence, each different allele codes for a variant form of the protein product of the gene. However, a locus can refer to any position on the chromosome, even a part that does not code for a protein or even a gene. Thus the term allele is sometimes applied to variant forms of DNA at non-protein-coding loci as well. The genotype of an organism for a particular gene is a listing of the types of alleles present at the locus which codes for the gene in the organism.
Conventions for describing parts of DNA molecules
Fig. 14. Banding patterns on human chromosome 1 Modified from the National Center for Biotechnology Information (NCBI) website.
Human nuclear chromosomes are numbered from 1 to 22 based on their size from longest to shortest. Each chromosome is divided into two "arms" by the centromere. The short arm is called the p (petit in French) arm and the long arm is called the q arm (for the next letter in the alphabet after p). When stained appropriately, the chromosome exhibits a distinctive banding pattern (Fig. 12), which makes it easier to differentiate the chromosomes under a microscope and which forms the basis for describing regions of the chromosome (Fig. 14). A shorthand code for a chromosome region (e.g. 1q25.2) consists of the chromosome number (1), arm (q), band (25) and sub-band (.2). Now that the human genome has been fully sequenced, basepairs on a chromosome are numbered beginning with 1 at the end of the p arm and continue through the last basepair in the chromosome (in the case of the longest human chromosome, chromosome 1, that number is 249250621). In other organisms there are different conventions for numbering.
There are several conventions for labeling the two strands of a piece of DNA depending on the frame of reference. In the human genome, the National Center for Biotechnology Information (NCBI) website uses the term "positive strand" to refer specifically to the strand whose 5' end begins at the end of the p arm. Basepair numbering starts at the 5' end of this strand (indicated in Fig. 14 by numbers such as 100M=100 megabasepairs). "Negative" refers to the other strand.
The two strands of a DNA molecule can also be described in the context of a particular gene. There is no general relationship between the "positive" and "negative" strands of a chromosome and the strand on which a gene is encoded because genes can be encoded on either of the two strands. The strand which contains the gene's nucleotide sequence is usually called the "sense" or "coding" strand. Its sequence is identical to that of the mRNA except for the presence of "T" rather than "U" (described in the following section). The complementary strand on which the mRNA is synthesized is usually called the "antisense" or "template" strand. Unfortunately, some people have used the terms "coding" and "template" strands in the opposite way, but the use described here is probably the most common. To further complicate things, the term "positive sense" strand is sometimes used for the sense (coding) strand, and "negative sense" strand for the antisense strand.
The term "downstream" is used to refer to the direction that the gene's sequence runs on the DNA molecule and "upstream" refers to the other direction.
Mitochondrial DNA is also part of the human genome, although it is not found in the nucleus and it has a chromosome that is circular (similar to that of a bacterium) rather than linear.
