A team of quantitative biology researchers from Northwestern University have uncovered new insights into the impact of stochasticity in gene expression, offering new evolutionary clues into organismal design principles in the face of physical constraints.

In cells, genes are expressed through transcription, a process where genetic information encoded in DNA is copied into messenger RNA (mRNA). The mRNA is then translated to make protein molecules, the workhorses of cells. This entire process is subject to bursts of natural stochasticity—or randomness—which can impact the outcome of biological processes that proteins carry out.

The researchers’ new experimental and theoretical analyses studied a collection of genes in Drosophila, a family of fruit flies, and found that gene expression is regulated by the frequency of these transcriptional bursts.

The Kingsley team pored over genetic data repositories, searching for places in the genetic code near the KITLG gene that tell the gene what to do. They found a location in the DNA where proteins known as transcription factors bind to the sequence and carry out the instructions specified in the code.

They discovered that if the nucleotide guanine holds that spot, the transcription factor cannot bind as tightly to the DNA as when another nucleotide (adenine) is in the same position. This simple alteration – replacing A with G in the DNA sequence – reduces the expression of the gene and, ultimately, changes the colour of the hair.

Guenther’s blue-flecked mice prove that the Kingsley group found the spot on the genome that informs hair follicles how much melanin to incorporate into hair.

Whole genome duplication followed by massive gene loss has shaped many genomes, including the human genome. Why some gene duplicates are retained while most perish has puzzled scientists for decades.

A study, published today in Science, has found that gene retention depends on the degree of “functional and structural entanglement”, which measures interdependency between gene structure and function. In other words, while most duplicates either become obsolete or they evolve new roles, some are retained forever because, evolutionarily speaking, they’re simply stuck.

“When we scan genomes there are some gene pairs that remain from whole genome duplication events that occurred millions of years ago,” says Elena Kuzmin, a co-lead author of the study and former graduate student who trained with Charles Boone, professor of molecular genetics in the Donnelly Centre for Cellular and Biomolecular Research, at the University of Toronto, who co-led the study.

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