Bioscientists solve gene mystery in mammals

Katherine Moss

A study led by scientists at Kent and Universitat Autònoma de Barcelona (UAB) has uncovered how the genome three-dimensional structure of male germ cells determines how genomes evolve over time.

Published in Nature Communications, the research has solved a mystery surrounding the origins of the rearrangement of genes in mammals, and opens new paths into investigating the genetic origin of genome structure in all organisms.

Dr Marta Farré Belmonte and Dr Peter Ellis from the School of Biosciences at Kent have been part of a team that has shown that sperm production is key to how regions of the genome are re-organised within and between chromosomes during evolution. In particular, inherited chromosomal rearrangements are associated with physical and biochemical processes that are specific to the final stages of sperm production, after the meiotic cell divisions have completed.

Comparison of genomes across many different mammalian species shows that while all species have a broadly similar catalogue of genes, these are arranged in a different order for each species and can be turned off and on differently. These rearrangements may affect gene function and regulation and, therefore, play a part in evolutionary changes and in defining species identity. Understanding how these rearrangements arise is therefore a key part of understanding genome form and function.

To study genome evolution, the team compared the genomes of 13 different rodent species and “unscrambled” the rearrangements that distinguish them. ‘This allowed us to work out the genome configuration of the rodent common ancestor and determine the locations of the evolutionary breakpoint regions (EBRs) participating in genome rearrangements’, explains Dr Marta Farré.

The research implies that males and females are not equal in terms of their impact on genome evolution. In particular, the team discovered that the evolutionary breakpoint regions (EBRs) participating in genome rearrangement were associated with regions that are active in later stages of spermatogenesis, when the developing male germ cells are called spermatids. Spermatids are cells undergoing the final stage of sperm development, after cell division has finished – and the events occurring during this process are male specific.

Dr Peter Ellis said: ‘Rearrangements occurring at EBRs were found to break and rejoin DNA stretches that are physically located close to each other in the spermatid nucleus. Of all the rearrangements that distinguish a mouse from a rat, a squirrel or a rabbit, the majority appear likely to have arisen in a sperm cell rather than an egg cell. For me, this shows that the male germline is the overall engine of genome structural evolution.’

The authors propose one explanation for their results is the different events that occur during egg and sperm cell production. While both sperm and egg cells reshuffle DNA during meiosis, the DNA breaks created during this process are repaired highly accurately. However, sperm cells also have to compact their DNA into a tiny volume to fit in the sperm head. This compaction causes DNA breaks and uses an error prone method to repair the DNA. Some of these errors can generate genomic rearrangements – explaining why sperm development is a critical factor in genome evolution.

While the study was carried out in rodents, spermatogenesis is a highly conserved process and therefore this principle is likely to apply widely throughout the tree of life, the researchers point out.

Participating in this study led by the UAB and University of Kent were also research teams from Josep Carreras Leukaemia Research Institute (IJC) and Sequentia Biotech.

Read the full release here.