Groundbreaking Israeli research challenges core assumptions of Darwinian evolution

Study by team at University of Haifa suggests genetic mutations are not always random, potentially reshaping science’s understanding of evolution.

By World Israel News Staff

A new study conducted by researchers in Israel and Ghana is challenging a core tenet of the traditional understanding of how biological evolution functions, potentially reshaping Darwinian theory.

The research was carried out by a team including scientists in Ghana and at Israel’s University of Haifa, led by Dr. Daniel Melamed, the lead author of the study, and Prof. Adi Livnat, director of the Sagol Lab for Evolution Research.

The team’s findings, which were recently published in the journal Proceedings of the National Academy of Sciences (PNAS), demonstrated that a key mutation in humans does not appear at random but instead manifests de novo significantly more frequently exactly where needed.

The mutation, known as APOL1 1024A>G, protects against African sleeping sickness while at the same time increasing the risk of kidney disease in people carrying two copies of the mutation.

Until now, Darwinian evolutionary theory has assumed that all genetic mutations are random, with beneficial mutations tending to be selected for – and thus preserved in the gene pool – by giving their carriers a greater chance at surviving and passing on their genes, while detrimental mutations tend to be removed from the gene pool by negative selection pressures.

Now, however, according to the work of the team in Ghana and Israel, it appears that mutations tend to occur more frequently in conditions where they are beneficial, with the APOL1 1024A>G mutation occurring far more frequently in sub-Saharan African populations than among Europeans – precisely where it is most likely to be protective, rather than a net negative, given its impact on kidney disease risk.

“These results are completely unexpected from the random-mutation point of view. From that view, individual mutations are not supposed to arise more frequently where needed,” said Livnat.

The findings mirror the group’s previous work showing that the HbS mutation, which protects against malaria while causing sickle cell anemia in homozygotes, originates de novo more frequently precisely in the gene and population where it is needed.

Livnat speculates that rather than being random, mutations are driven by some previously unrecognized internal force operating inside the organism, which assembles genetic information that has accumulated internally in the genome over generations in useful ways.

Work by Livnat’s team, for instance, appears to show that fusion mutation – where two genes fuse to form a new one – is not a random process, but is instead driven by some patterns established over generations.

Because the genome folds in 3D space, bringing genes that work together to the same place and time in the nucleus, molecular mechanisms fuse these genes rather than others, “hardwiring” long-standing biological interactions into simplified genomic instructions.

The study’s authors also argue that single-letter changes are implemented by complex regulatory phenomena at each generation at the RNA level, making changes over generations more likely to be “hardwired.”

In the PNAS paper, the team argues that fusions and RNA editing are merely two examples of a general principle that applies across mutation types.

Rather than local accidents disconnected from other genetic information, mutations combine and integrate genetic information into streamlined instructions. Over the generations, and with feedback from natural selection, interconnected mutational activity enables long-term directed mutational responses to specific environmental pressures, as shown by the APOL1 and HbS mutations.

“Previous studies examined mutation rates as averages across genomic positions, masking the probabilities of individual mutations. But our studies suggest that, at the scale of individual mutations, each mutation has its own probability, and the causes and consequences of mutation are related,” Livnat said.

“Not only are gene fusion mutations nonrandom, their mechanism of origination is actually analogous to one of the most basic principles of cognition and learning in the brain.”