Abstract:
Some genetic changes in human sperm may occur earlier than science has long thought, a new study suggests. Some of the DNA recombination processes that determine the genetic diversity of offspring do not all occur during the meiosis stage required to produce sperm, but may have begun earlier during cell development.
This research published in the journal Nature was jointly completed by the Sanger Institute in the UK, the University of Cambridge and a number of collaborating institutions. The study focused on a genetic phenomenon known as "non-exchangeable gene conversion." In this process, one chromosome copies a small sequence of DNA from its counterpart, changing the version of the genetics carried at a certain location.
Each child inherits a set of chromosomes from his parents, but this genetic information is not simply copied and passed directly to the next generation. During the formation of sperm and eggs, genetic material undergoes complex recombination, giving offspring a unique combination of genes.
The scientific community generally believes that these recombinations occur mainly during meiosis. The traditional view is that the two main genetic recombination mechanisms, including "cross-over", which involves large-scale bidirectional exchange of chromosome segments, and "non-exchange gene conversion", which copies short segments of DNA, are part of the meiosis process.
New research, however, challenges this long-held view.
The researchers pointed out that before entering meiosis, the precursor cells that will form sperm have actually undergone multiple rounds of ordinary cell division, that is, mitosis. These cells are constantly renewed throughout a man's life to maintain continued sperm production.
To determine whether some gene conversion events might occur at this early stage, the team analyzed 15 sperm samples from 13 male donors, ranging in age from 24 to 74 years old.
With the help of high-precision long-read DNA sequencing technology, researchers can directly observe long fragment information in single DNA molecules, thereby discovering many tiny recombination events that are difficult to detect with traditional sequencing methods.
The analysis results showed that the research team identified a total of 7143 crossover events and 2382 non-exchange gene conversion events in sperm DNA.
The researchers then compared these results with blood DNA samples and data from previous published studies. The results showed that a considerable proportion of non-exchange gene conversions did not have typical meiosis characteristics, but were more like the result of DNA repair formed before entering meiosis.
Further analysis showed that these events were weakly associated with hotspots of DNA breaks that typically occur during meiosis and lacked many of the genetic signatures that researchers expected. Instead, they appear more often in fragile regions of the genome that are prone to DNA damage and breaks.
The research team also found that similar patterns not only existed in sperm samples, but related signals could also be observed in blood DNA. Blood cells do not undergo meiosis, so this result further supports the idea that some gene conversion may result from DNA repair activities during ordinary cell division.
The researchers believe this means that genetic recombination in male germ cells may actually occur in two stages. The first phase occurs during the daily division of sperm precursor cells, and the second phase occurs during meiosis in the traditional sense.
In addition, studies have found significant differences between individuals. Even identical twins with highly identical genetic backgrounds do not have exactly the same pattern of partial gene conversion in their sperm. This suggests that such genetic changes are not entirely determined by genetic factors but are influenced by independent biological events during an individual's life.
Scientists said that this discovery not only changes the understanding of the mechanism of sperm formation, but also provides a new perspective for studying genetic diseases, male fertility and the long-term evolution of the genome.
The research team believes that further analysis of these early DNA repair and recombination processes in the future may help explain the origin of certain genetic variations and why some disease risks undergo complex changes in family inheritance.
With the continuous advancement of sequencing technology, scientists are gradually discovering that the formation process of human genetic diversity is far more complex than previously understood. This study shows that some important changes that determine the genetic differences of offspring may have occurred quietly many years before the sperm enters the final stage of maturation.
Comments