Mutation rates and paternal age

Tags

biology, evolution, genetics, iceland, mutation, nature, science

I briefly want to talk about a newly minted shiny article published in one of the scientific ‘glossy’ journals, those high-profile journals that lead to the bulk of the science-news coverage. This one was published in Nature a week or so ago.

I wanted to wait a bit before writing about it, and now that we are nearing the end of the typical article news cycle (1-2 weeks) it is time. Here is the main conclusion from the article: older fathers pass-on more new mutations to their children than younger ones. The most important background fact is that mutation is the stuff of evolution. It is the raw change that allows all organisms on earth to adapt. Biologists generally hypothesize that mutation rates are constant, meaning that DNA changes accumulate at a certain rate as organisms age. In a recent work Augustine Kong potentially challenged that idea (see main article figure below).

Some mutations are linked to disease, a child with more mutations is at higher risk, just by laws of probability, of getting the ‘disease’ mutation. Importance of this data to the realm of human disease is obvious. The substantial media coverage following Kong’s publication almost entirely focused on the disease aspect. Here are some headlines from the usual suspects: “Older fathers linked to Kids’s Autism and Schizophrenia risk” says Time Magazine, “Older dads may raise risk for autism in kids” adds FOX, “Father’s age is linked to risk of autism and schizophrenia” finishes the New York Times while omitting the kids aspect in their title all together.

Here is what the headline, in my opinion, should of read “Mutation rates are not constant, new Iceland population study suggests.” It is not an especially catchy title and I see that. Disease is bad for people, good for biologists. Biologists sell their work and build careers by putting words like, disease, autism, dawns, and MS into the titles of their papers and grants. Augustine Kong is not first to insight  media frenzy with ‘disease’, and that’s OK because journalists got to do their job and no story sells better than a story that everyone is afraid to hear.

I read the journal article and swam the sea of biased media coverage waiting for the bile and rage to loosen its grip. Then I wrote this, and tried to mention the real interesting bit, the implications of this work on how biologists estimate divergence. Mutations are assumed to accumulate in a clocklike way, same rate over time for each type of organism. This allows comparisons between organisms, like humans and monkeys and squid and bacteria. Because of this constant ‘mutation clock’ biologists are able to say that genetically humans and monkeys are more similar that humans and tomatoes. Because of this ‘mutation clock’ biologists can estimate how long it takes for organisms to diverge and become different enough to be considered different species.

What Augustine Kong and friends showed is that the mutation rate is not constant, and they were as far as I know the first ones to actually calculate the rate of mutation increase with age.

With age fathers ‘give’ more new mutations to their children. Mechanistically, from the cell biology point of view, this implies that as males age they incorporate more genetic mistakes during sperm production. This is also extremely interesting. In males, the machinery that proofreads DNA replication during sperm formation may degrade with age. This last one is a crazy idea and there is very little substantial proof behind it, but it points to an interesting question of how these new mutations appear.

I want to end with this final point, it may be subtle and it is definitely intuitive. Demography matters. Kong’s work did move biology forward, and strengthened the link between the important ideas of genetics and demography. It is important when we mate and how many offspring we produce and how well we feed the first and the last ones.

Contributor Artur Romanchuk is a fifth-year graduate student at UNC Chapel Hill studying with Christina Burch and Corbin Jones. Artur primarily studies how bacteria pass genes to one another (“lateral transmission”) and how these new genes lead to the ability to infect new hosts. He is also an author and cartoonist: check out his other works at ingradients and WHandCats. His first daughter was born when he was in his mid-twenties, and should be relatively mutation-free.

Related articles

• More mutations in children of older fathers, and how it relates to human origins (dienekes.blogspot.com)
• Human Mutation Rate Is Gender Biased And Low (dispatchesfromturtleisland.blogspot.com)
• Father’s Age Affects Mutation Rate (the-scientist.com)
• Whole Genome Sequencing of Mutation Accumulation Lines Reveals a Low Mutation Rate in the Social Amoeba Dictyostelium discoideum (plosone.org)