Variety is the spice of life, they say, but where does variety come from? Genetically speaking, it comes from mutations. And sex, but we’ll get to sex later. This post is about mutations.
Without mutations, we would all be clones of one another. More precisely, without mutations, we would all be clones of tiny, bacteria-like cells stuck in the muck on an oxygen-less planet. Without sex.
This could be us:
Let’s hear it for mutations, folks!
What Is a Mutation?
A mutation is a change in the sequence of nucleotides that make up the DNA. Mutations can be small (affecting only one or a few nucleotides), large (rearranging a large chunk of the genome), or somewhere in between.
Recall from an earlier post in this series that DNA is made up of two long strands (polymers) of four units (nucleotides, a.k.a. bases) that are held together by weak bonds (hydrogen bonds). The bases on one strand pair up with the bases on the other strand in a very specific way: A always pairs with T, and C always pairs with G.
The “complementary” pattern of DNA is sublimely elegant, for two main reasons. First, if one strand of the DNA is damaged, it can be repaired by cribbing off the other strand. For example, in the image above, if the GT on the upper strand were altered by some chemical misfortune, that strand could be fixed by cutting out the damaged nucleotides, pairing the C and A on the intact bottom strand with new G and T nucleotides, and restoring the strong bonds holding the upper strand together. In fact, our cells have special enzymes (chemical robots) that do precisely that, scanning up and down the DNA looking for damage to fix, like a maintenance crew.
Second, the complementary nature of DNA can be used to duplicate entire genomes. The weak bonds in the double helix are simply “unzipped”, as shown below, and new copies of the upper and lower strands are made from scratch using the base-pairing rules. This is called DNA replication. (In practice, it’s not nearly so simple, of course.)
The enzymes involved in repair and replication of DNA are called DNA polymerases. (Hint: In biology, if the word ends with –ase, it’s an enzyme, and the first part of the name usually tells you what the enzyme does. A DNA polymerase makes or repairs DNA polymers.) Mutations occur when DNA polymerases either mess up or when the damage is too severe for them to repair.
Mutations can kill us, harm us, or benefit us. Usually, though, they have no effect at all. Remember that most of our DNA doesn’t seem to do anything. Alterations to this so-called “junk DNA” are considered neutral, because they neither hurt nor help us. They can be quite useful for genealogy, though.
Not all mutations are passed on to our offspring. It depends on when and where in our bodies they occur. A mutation in a single egg or sperm, or in the tissues that produce eggs and sperm, would be present in the resulting child, but a mutation elsewhere in the parent’s body would not. For example, I could develop skin cancer from a mutation and still produce normal eggs. The mutations that matter for genealogy are the ones that are passed on.
Types of Mutations
Mutations come in several flavors, some of which are relevant to genetic genealogy.
- A point mutation is a change in a single nucleotide. It happens when the wrong nucleotide is used during either DNA replication or repair. Point mutations are relatively rare. For that reason, if two people have the same point mutation, it’s much more likely that it occurred once in their common ancestor from whom they both inherited it rather than twice in the exact way and exact same spot in two separate people. (The latter can happen, of course, but that’s not the go-to assumption in the genealogical time frame.) Point mutations that are common enough in a population to potentially tell us about relationships (usually considered to be a 1% frequency or higher) are called single nucleotide polymorphisms, or SNPs. SNPs (pronounced “snips”) are important to autosomal, mitochondrial, and Y DNA testing.
- Insertions and deletions, collectively called indels, change the length of a DNA strand by adding or deleting nucleotides. The term “indel” usually refers to short segments (one or a few nucleotides), but there’s no hard-and-fast cut-off. Simple indels are not terribly important in genetic genealogy, but they can sometimes show up in your results. For example, you may be missing a certain SNP because your lineage experienced a deletion at that position.
- A special type of length mutation occurs in short tandem repeats (STRs, also known as microsatellites). The mechanism is unique enough that STRs are considered distinct from regular indels. STRs are short sequences of DNA that repeat over and over again, back to back. They’re usually 3–5 bases long and can repeat 5 to 50 times. STR mutations happen when the DNA polymerase slips during replication and adds or omits a copy of the repeat sequence. In genealogy, we analyze STRs on the Y chromosome to compare male-to-male lineages. (Some autosomal STRs are also used by law enforcement in criminal DNA databases.)
- There are several other types of mutation, including gene duplications, “jumping genes” that move from place to place in the genome, inversions that flip the orientation of a sequence, and major structural rearrangements that are usually quite harmful. These other mutation types do not have genealogical uses at the moment, although that may change with the advent of whole genome sequencing.