HOW OVER A METRE OF HUMAN DNA IS PACKAGED INTO A TINY SPERM CELL
 
CRG researchers describe how the human genome is packaged into a single sperm cell and why this may be important for the evolution of genomes and the regulation of genes during development.
 
All cells of an individual contain the same genetic information encoded in the sequence of their DNA. In most cells this DNA is wound around protein complexes called nucleosomes that keep it compacted and regulate how genes are turned on or off.  However the male gametes – sperm – are different.  In sperm, DNA must be even more tightly compacted to fit into the tiny sperm head.  As a result nucleosomes are only retained at a few sites, being replaced across most of the genome by other proteins that lead to higher compaction.
 
In work recently published in PLoS Genetics, Tanya Vavouri, researcher at the CRG and now group leader at the Institute of Predictive and Personalized Medicine of Cancer (IMPPC) and Ben Lehner, ICREA research professor and head of the Genetic Systems laboratory at the EMBL-CRG Systems Biology Research Unit, describe how these sites of nucleosome retention in sperm are specified.  They found that it is the sequence of the genome itself that determines where nucleosomes are retained.  DNA consists of four bases – A,T,C, and G – and it is the number of G and C bases that is important for the retention of nucleosomes in mature spermatozoa.
 
Tanya Vavouri, who performed the research, commented, “for a long time it has been known that the human genome shows local variation in the content of G and C versus A and T bases.  Our work suggests that a significant reason for this variation may be to specify how DNA is packaged into sperm so that it can be transmitted to the next generation.”
 
“Strikingly nucleosomes are retained in sperm right at the start sites of some of the most important genes”, added Lehner.  “Nucleosomes are known to be modified in sperm, and so at these locations they may be transmitting extra information to the next generation that is not encoded in the sequence of the DNA.  This is a really exciting idea that should be investigated more in the future”.
 
Reference: Vavouri T, Lehner B (2011). “Chromatin Organization in Sperm May Be the Major Functional Consequence of Base Composition Variation in the Human Genome”. PLoS Genet 7(4): e1002036. doi:10.1371/journal.pgen.1002036