Neurons with heavily altered genomes become rarer around birth
A peer-reviewed study of human brain tissue found that neurons carrying extensive chromosome-copy changes were less common after birth. The difference between age groups supports a model of developmental cell selection. Smaller changes declined more gradually, while surviving neurons carried fewer alterations affecting sensitive genes. Individual cells’ fates were not followed over time.
Science··Morning
Extensive chromosome changes decline around birth
Neurons with heavily altered genomes were markedly less common after birth in a peer-reviewed study of human brain tissue. Researchers examined 2,357 individual neurons from postmortem brains across different ages. Before birth, an average of 25.9 per cent of cortical neurons carried extensive copy-number changes spanning multiple chromosomes. Their proportion was about 4.5 times lower after birth. Copy-number changes mean that sections of DNA have been gained or lost, changing how many copies a cell carries.[1], [2]
Smaller changes follow a slower pattern
One genomic approach covered 1,526 neurons from 16 people, and another covered 831 neurons from 12 people. Both supported the broad age pattern. The sharp age difference in extensive abnormalities was distinct from the slower postnatal decline among neurons with smaller copy-number burdens. Surviving neurons had relatively fewer changes affecting genes sensitive to dosage and genes associated with nervous-system development. Those patterns support a model in which selection during development changes the genetic composition of the surviving neuron population. Individual neurons were not followed over time; the age groups contained cells from different people.[1]
Gene activity offers a link to cell survival
Analysis of gene activity and access to genetic material in 44,861 nuclei found disrupted synaptic gene programmes in neurons with high copy-number burdens. Synapses are the connections through which nerve cells communicate. The findings connect abnormal genomes with changes in the programmes needed for those connections, offering a possible link to cell survival during development.[1]
Micronuclei, small structures containing genetic material outside the main nucleus, and signs of replication stress provide further clues. The timing of the decline overlaps periods of programmed cell death, but the elimination mechanism remains an interpretation. Agreement between separate genomic approaches reduces concern about an artefact of one technique. Samples from different people cannot reconstruct the same developing brain continuously; implications for developmental disorders remain questions for further investigation.[1]
