Hidden source of genetic diversity found in human sperm

Amazing stuff!

"... Scientists have identified an unexpected source of genetic variation in human sperm that occurs earlier in sperm development than previously thought. ...

researchers ... found that one type of genetic recombination involving the chromosomes, called non-crossover gene conversion, happens before the cell divisions that produce sperm.

The findings suggest that genetic recombination events in sperm happen in two stages, both before and after cell division. The team found that these DNA recombination patterns can vary between individuals, including between identical twins. This study opens new opportunities to investigate biological mechanisms underlying fertility, genome evolution and inherited disease. ..."

From the abstract:

"Meiotic recombination is a fundamental process that generates genetic diversity by creating new combinations of existing alleles. Whereas crossovers in humans are well characterized, the more frequent non-crossovers that lead to gene conversion remain challenging to study.

Here we show that single high-fidelity long sequencing reads from sperm can capture both crossovers and non-crossovers, which enables effectively arbitrary sample sizes for analysis from a single male.

We analysed 2,382 candidate non-crossovers in 15 sperm samples from 13 donors, and identified a consistent component with properties distinct from PRDM9-induced recombination.

This phenomenon was not associated with meiotic double-strand break sites identified by DMC1 binding, the crossover recombination map or GC-biased gene conversion, but was associated with genomic fragile sites.

This component is also seen in paternal non-crossover gene conversions in pedigree data.

Applying the same analysis to 12 blood samples, we observed non-crossover gene conversions with similar properties, but very few crossover events.

Further, we demonstrate variation between donors for the different types of recombination, even when they share the same PRDM9 genotype.

We suggest that a substantial fraction of the non-crossover gene conversion events seen in sperm arise prior to meiosis."

Hidden source of genetic diversity found in human sperm "New research provides a detailed view of how genetic diversity is generated in sperm and opens new opportunities to investigate the biological mechanisms underlying fertility, genome evolution, and inherited disease."

Long-read sequencing reveals pre-meiotic gene conversion in sperm (open access)

Fig. 1: Detecting recombinant reads in sperm samples.

Fig. 4: Origins of meiotic and pre-meiotic recombination events in the male germline.