3.7: Mutations and the origins of genotype-based variation

Where does inheritable variation come from? How do genotypes change? As a simple analogy, we can think of the genotype as the book that contains the instructions to build the tools and parts needed to form and maintain a specific, individual cell/organism. This book, known as the genome. is complex - it contains both instructions but also codes that determine when particular instructions should be read. The complexity comes from how the genome "works". In humans, this involves DNA molecules that taken together are approximately 3.2 billion base pairs long. Within these DNA molecules there are regions that appear to be meaningless (but may not be) and those that clearly encode specific instructions. To continue our analogy, a few changes to the DNA sequence may have no effect on meaning, while others may dramatically change the narrative or make no sense at all. Do not worry, much more on DNA later.

At this point we will define the meaningful regions, the words and sentences, as corresponding to genes and the other sequences as intragenic regions, that is, spaces between and within genes. It has been estimated that humans have ~25,000 genes. As we continue to learn more molecular biology, our understanding of genes and intragenic regions has become more nuanced. Regions that originally appeared meaningless have been found to have meaning. Many regions of the genome are unique, they occur only once within the string of characters. Others are repeated, sometimes hundreds to thousands of times. When we compare the genotypes of individuals of the same type of organism, we find that they differ at a number of places. For example, over ~55,000,000 variations have been found between all human genomes examined to date, and more are likely to be identified. These genotypic differences are known as polymorphisms, from the Latin meaning multiple forms. Polymorphisms are the basis for DNA-based forensic identification tests. One thing to note, however, is that only a small number of these variations are present within any one individual, and considering the size of the human genome, most people differ from one another at less than 1 to 4 letters out of every 1000. That amounts to between 3 to 12 million letter differences between two unrelated individuals. Most of these differences are single characters, but there can be changes that involve moving regions from one place to another, or the deletion or duplication of specific regions.

In sexually reproducing organisms, like humans, there are typically two copies of this book in most types of cells of the body, one derived from each of the organism’s parents. Organisms (and cells) with two genomic “books” are known as diploid. When a sexual organism reproduces, it produces cells, known as gametes: sometimes these are the same size. When gametes differ in size, the smaller one is known as a sperm and the larger is known as an egg. Each gamete contains one copy of its own unique version of the genomic book and is said to be haploid. This haploid genome is produced through a complex process known as meiosis (considered in Chapter 11). Meiosis leads to a shuffling of the organism’s original parental genomes. When a haploid sperm and a haploid egg cell fuse, a new diploid organism is formed with its own unique pair of genomic books..

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