This video produced by Cold Spring Harbor Laboratories takes us on a tour of about 650,000 nucleotides from the tip of the short arm of human chromosome 11. From a distance we can discern 28 genes, denoted by red and yellow blocks. The red exons carry the DNA code for protein, while the yellow introns are noncoding. Also prominent are more than 500 transposons, or jumping genes, denoted by blue and purple blocks. If we zoom in, we can take a closer look at the structure of this chromosome region. We first encounter a cluster of five small genes, averaging about 1,500 nucleotides in length. These encode components of hemoglobin protein, the oxygen carrying molecule of the blood. Beta globin is a common component of adult blood, and a mutation to a single nucleotide in this gene is responsible for sickle cell anemia. Delta globin, a minor component of adult blood, is followed by a nonfunctional copy of beta globin, termed a pseudogene. Gamma and epsilon globins are expressed in the embryo and fetus.
Next we encounter two small genes that encode olfactory receptors, common features of Chromosome 11. These are followed by an intergenic region of 183,000 nucleotides, lacking any known genes. Scattered throughout this region are numerous “simple repeats” composed of multiple copies of a repeated sequence of 2-50 nucleotides. Two green blocks identify repeats longer than 100 nucleotides. Variations in the number of repeats among people, create a DNA difference, or “polymorphism,” which can be used in forensic biology, paternity testing, or disease diagnosis. Blue and purple boxes identify the more than 100 transposons that litter the intergenic region. These molecular parasites make up about half of the human genome by weight, and the majority move about using an enzyme that was later borrowed by viruses such as HIV. Each of the millions of transposons in the human genome arose from an individual “jump” at some point in evolution. The majority of transposons have not jumped for millions of years and, thus, are “molecular fossils.” As we will see, the majority of transposons are located within gene clusters and even within genes – a fact that perplexes scientists.
The intergenic region is followed by two adjacent ubiquilin genes, which are involved in key cell processes, from replication to programmed cell death also known as “apoptosis”. ubiquilin 3 is expressed specifically in the testis, where it is believed to help regulate sperm development. These are followed by a cluster of gene locations (LOC) thought to encode olfactory receptors, which receive stimuli in the nose to allow us to detect smells. At 31,110 nucleotides long, the first gene in this cluster, LOC120009, is the longest we will encounter on our journey. Its 11 coding exons are indicated in red, but most of its bulk comes from its yellow introns and 29 blue and purple transposons. However, the majority of olfactory receptors are short. The next four gene locations are more typical of olfactory receptors in having only one or two coding exons. About 60% of our smell receptors are nonfunctional. Presumably, humans have less need for smell in locating food and interacting socially. The mutations that inactivate many receptors vary among people, meaning that there is a DNA basis for the observation that some people can smell better than others! It also suggests that the loss of smelling acuity has occurred very recently in human evolution and is still ongoing.
Next follows a cluster of four genes in the tripartite motif (TRIM) family. TRIM proteins contain three motifs, or structures, through which they bind to DNA to regulate gene activity. Averaging about 21,000 nucleotides and having about eight coding exons, the TRIM genes come very close to the average size of human genes. Different proteins can be produced by a single TRIM gene, by making different combinations of coding exons. TRIM 34 and 22 help mediate the antiviral activity of interferon and offer insight into the fight against HIV. Our tour ends with another cluster of nine olfactory receptor genes (LOC). Chromosome 11 contains about 40% the estimated 1,000 genes for olfactory receptors in the human genome. There is such a concentration of receptor genes at the tip of Chromosome 11 that this whole region could be called an olfactory supercluster, in which the beta globin, ubiquilin, and TRIM clusters are embedded.