Breakthrough in Understanding Human Evolution Due to Computational Genomics

The fragile regions in mammals’ genomes that are thought to play a key role in evolution go through a "birth and death" process, according to new work by University of South Carolina and University of California-San Diego researchers.

The study, published in the journal Genome Biology, could help researchers identify the current fragile regions in the human genome – information that may reveal how the human genome will evolve in the future.

“We made a step towards understanding the mechanism of genome rearrangements that ‘shuffle’ genomic architectures and represent one of the major driving forces behind evolutionary diversity. In contrast to previous studies, our results allow one not only to analyze the evolution in retrospect but also to predict the future changes in genomic architectures,” said Dr. Max Alekseyev, one of the study’s authors and a computer science and engineering professor in the College of Engineering and Computing at USC. Alekseyev worked with Dr. Pavel Pevzner from UC-San Diego. The two researchers study genomes and genome evolution from a computational perspective.

An important question in evolutionary studies is whether there are "fragile" regions where genome rearrangements are happening over and over again. The fragile regions are prone to “genomic earthquakes” that can trigger genome rearrangements, disrupt genes, alter gene regulation and otherwise play an important role in the evolution and emergence of new species. For example, humans have 23 chromosomes while some apes have 24 chromosomes, a consequence of a genome rearrangement that fused two chromosomes in our ape ancestor into human chromosome 2.

Although nearly all recent studies support the existence of these fragile regions, there have been some doubts about their existence, raised from a comparative analysis of multiple mammalian genomes.
“Our findings imply that fragile regions migrate to different locations in different mammals, and it explains why there are only a few fragile regions shared between different lineages,” said Alekseyev.

The research demonstrates that the fragile regions undergo a birth and death process over evolutionary timescales and provides a clue to where the fragile regions in the human genome are located. The researchers conclude that these regions in the human genome are likely to be affected by the coming genome rearrangements. “We hope that further analysis of the identified fragile regions in the human genome would provide insights into current trends in the human evolution”, said Alekseyev.

The researchers are now working on confirmation of a conjecture that genomic fragility is promoted by matching segmental duplications.

The researchers also hope that their approach may be useful for understanding genome rearrangements at the level of individuals, rather than entire species. In the future, they plan to apply similar analysis for the genome rearrangements that occur within the cells of individual cancer patients in order to develop new cancer diagnostics and drugs.