Every child inherits roughly 60 brand-new mutations that neither parent carried
Each of your cells suffers around 10,000 bouts of oxidative DNA damage a day, and repair crews fix nearly all of it. The slips that survive become mutations. On average a child arrives with about 60 new ones, and each extra year of a father's age adds roughly two more.
A mutation is a change in the sequence of DNA or RNA. It differs from DNA damage, which is a physical defect such as a broken strand or a chemically altered base. Enzymes can spot damage and repair it using the intact partner strand, but once a changed letter appears on both strands the cell sees nothing wrong, so the mutation is copied every time the cell divides. Damage and mutation are linked all the same: copying past damaged DNA is a major source of errors, causing most mutations in mice and more than 60 percent of single-letter changes studied in yeast.
Mutations arise in several ways. Some are spontaneous chemistry, such as a hydrogen atom shifting so a base pairs with the wrong partner, possibly helped by quantum tunnelling of protons. Others come from sloppy repair of double-strand breaks, or from mutagens in the environment. One 2017 study across 69 countries estimated that 66 percent of cancer-causing mutations are random, 29 percent environmental and 5 percent inherited.
Most mutations change nothing that matters to survival, and a 2007 study of fruit flies estimated that about 70 percent of changes that alter proteins are harmful. Yet mutation is the ultimate source of all genetic variation. Duplications of chunks of DNA supply spare gene copies free to take on new jobs, and an animal genome picks up somewhere between tens and hundreds of duplicated genes per million years. Human eyes rely on four light-sensing genes, three for colour and one for night vision, all descended from a single ancestral gene.
Bigger rearrangements can help split species. Two ancestral chromosomes fused to form human chromosome 2, a merger other apes never underwent, so they keep the pair separate. Mobile DNA reshapes genomes too: the human genome holds more than a million copies of the Alu sequence, some now recruited to regulate genes.
Source: Mutation
