In October 2004, the study of human biology reached a watershed landmark: the complete human genome was deciphered. Despite the fact that we humans all too often focus on our differences, it was quickly discovered that, by and large, no matter how dissimilar we look or behave, we share most of our genome with each other.


The human blueprint

The complete set of instructions for every detail of our body’s structure and all its functions is contained in our DNA. DNA is made up of four different bases: adenine, thymine, cytosine, and guanine (or A, T, C, and G for short). These bases combine in different threesomes to form “letters” that are the code of life. For example, one letter of the code can be ATG, while another could be CGT, and so on. Each triplet codes for one of the 20 amino acids that are the building blocks of all proteins and peptides.

These bases are quite stable chemically, but nothing is 100%—and this includes the bases. When one of the bases undergoes a chemical change, say from A to G or C to T, this is known as a point mutation. When a point mutation “slips by” unnoticed by the translating mechanism that converts the base sequence into amino acids, then an amino acid different from the original will be incorporated into the protein. The consequences of that substitution can range from no effect to very severe compromise of the protein’s physiological function. For instance, a point mutation in the code for the hemoglobin protein results in a profound change in its structure, which in turn results in the blood disorder, sickle cell anemia.

Some scientists thought that such ostensibly minor changes, such as point mutations, might account for not only the different susceptibilities of individuals to a variety of diseases, but also for our very individuality. This tantalizing hypothesis raised the need to sequence the genomes of many individuals. Indeed, an international project to map these point mutations, called the HapMap, is underway.


Patchwork people

No sooner did this project get underway that a flood of reports from different labs pointed out much “bigger” mutations. In a review published in Nature (Nature, vol.437, pp. 1084-1086, 2005), Erika Check describes several classes of mutations that hold the promise of defining what makes us different from chimps, what defines our individuality, and what makes us susceptible to a variety of diseases.

Imagine three genes strung out next to each other on the DNA: A-B-C. It can happen that one of those genes, let’s say B, is simply deleted and you are left with the two gene sequence, A-C. Mutations of this type are known as deletion mutations. Insertion mutations also occur (e.g., a D gene is inserted into the A-B-C sequence, resulting in a new code: A-D-B-C). A sequence of genes can get inverted, changing an A-B-C sequence into a C-B-A sequence. A gene can get duplicated (A-A-B-C) or a whole segment can get duplicated (A-B-C-A-B-C).

It seems that there is no end to the genome’s tricks. These changes, however, are no joke. New gene sequences can change the structure and function of key components of our body.

Given that, these really quite amazing “mistakes” in our genome are apparently quite common. And, they are particularly common in gene groups that are responsible for interaction with the environment. Some mutations are deleterious and lead to disease or death. However, others are not.

A tantalizing possibility is that the patchwork of mutations that we all carry may actually determine our very individuality. These genomic “mistakes” may, in fact, be the reason that, despite having largely similar genomes, I am different from you and we both are different from chimps.

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.