To form an egg or sperm cell, a cell splits into two during meiosis so each resulting cell only contains half the chromosomes of the original.

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Gene-swapping in human sperm and eggs can increase genetic mutations in children

When parents pass their genes down to their children, they give the kids remixed versions of their own chromosomes. And that remixing of chromosomes can increase the chances that the child’s DNA will also mutate in certain locations, according to a high-precision study of the DNA of more than 150,000 people. The data in this study may be helpful for understanding mutation rates in humans and measuring how quickly we are evolving.

“The scale of the study is just unprecedented,” says geneticist Molly Przeworski of Columbia University, who was not involved in the project. “The resource alone is going to be a boon for the field.”

Your genome consists of long strands of the double-helix molecule DNA, which codes for your genes using the four chemical letters of life’s genetic alphabet. A total of about 3 billion pairs of letters, or “base pairs,” coil into 23 pairs of chromosomes in almost every one of your cells. Each chromosome can contain hundreds to thousands of genes, stretches of DNA that spell out the chemical recipes for myriad proteins.

To pass genes down to their children, parents split specialized cells called germ cells to create egg and sperm cells that each contain 23 chromosomes—half of the genetic material in the original germ cell. But before a germ cell splits, each chromosome swaps a chunk of itself with its partner chromosome in a process called recombination or “crossover,” because segments of DNA cross over between chromosomes in a pair. As a result, offspring won’t have chromosomes identical to that of their parents.

Now, data show such crossovers may affect the rates at which individual genes mutate. Using a genetic data set of 155,250 Icelanders, researchers at deCODE Genetics, a biotechnology company based in Reykjavik, have created the most detailed map yet of the relative locations of genes on the human genome. By looking at the differences in parent and child DNA, the researchers could trace both crossovers and mutations in DNA as it passed from parent to child. Previous genetic maps revealed the locations of specific features to within thousands of DNA base pairs. The new map lets researchers pinpoint the location of a feature to a segment of DNA about 700 base pairs long.

The team found that mutations occurred much more often near crossover sites, as they report today in Science. In stretches of DNA within about 1000 base pairs of where crossovers had happened, mutations were roughly 50 times more common than in the whole genome on average. And the farther from a crossover site a stretch of DNA was, the fewer mutations it had.

Past studies have shown similar relationships between crossovers and mutations but in less detail. Because the crossovers that occur when parents’ sex cells are created are not random, they make mutations more likely in certain areas of DNA, making these mutations less random as well. “It points us to the very fact that there’s more than randomness to [the] generation of genetic diversity,” says neurologist Kari Stefansson, CEO of deCODE Genetics and an author on the new paper. Understanding how mutations happen can help biologists study how genetic diversity is created in the species and lend insights to the study of mutation-caused diseases as well.

Parents’ ages also seem to matter. For each year older that a father or mother is when their child is born, the number of mutations in the child’s DNA will increase by about 1.39 and 0.38 respectively, the researchers find.

A mother’s age also affects the number of crossovers a child will inherit, the study reports. For older mothers, the egg cells that eventually become offspring tend to have more crossovers than the egg cells of younger mothers.

Aside from findings about crossover and mutation frequencies, the researchers identified several specific genes that might be associated with the rate or location of crossovers beyond the genes researchers already knew about. These genes and their possible connections to crossovers open new paths for research, Przeworski says.

The project may be useful for researchers who study human evolution. Geneticist Priya Moorjani of the University of California, Berkeley, who was not involved in the study, uses mutation rates in DNA as a clock for measuring how much time has passed since certain events in our evolutionary history. The data in this study may be helpful for learning what might control mutation rate and make our understanding of evolutionary timelines more precise, she says.