Capturing a Hard-Wired Variability: What Makes Some Identical Twins Noticeably Different?
A Ludwig Cancer Research study has uncovered a phenomenon that alters prevailing views of how the genome is expressed to make and sustain the life of mammals. Published in the journalScience, the paper helps explain why genetically identical animals are sometimes so different in their biology and appearance, and why some inherited disorders caused by a shared set of aberrant genes can be of such variable severity in different people.
"We have captured a fundamental randomness at the level of gene expression that has never before been described — one that persists throughout development and into adulthood," says Ludwig scientist Rickard Sandberg at the Karolinska Institutet in Sweden. The discovery was made possible by a powerful new technique developed by Sandberg’s lab for analyzing the global expression of genes in single cells.
With the exception of a subset of genes found on sex chromosomes, every mammal inherits one copy of every gene from each of its parents. Each of those copies is known as an allele, and alleles often differ measurably from their genomic siblings — a fact that accounts for a good deal of human and animal diversity. It has, however, long been unclear whether each allele in any given cell or organism is expressed equally, or whether one allele is favored over the other. The current study finds that only one allele is expressed in between 12 and 24 percent of all such pairs encoded by the mouse genome. Further, the selection of expressed alleles varies randomly from cell to cell, and switches frequently between the two options throughout their lives.