Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Flipped genetic sequences illuminate human evolution and disease

26.10.2005


By comparing the human genome with that of the chimpanzee, man’s closest living relative, researchers have discovered that chunks of similar DNA that have been flipped in orientation and reinserted into chromosomes are hundreds of times more common in primates than previously thought. These large structural changes in the genome, called inversions, may account for much of the evolutionary difference between the two species. They may also shed light on genetic changes that lead to human diseases.



Although humans and chimpanzees diverged from one another genetically about six million years ago, the DNA sequences of the two species are approximately 98 percent identical. Given the 2005 publication of the draft chimpanzee genome sequence, researchers can now readily identify the differences between the human and chimp genomes. These differences lend insight into how primates evolved, including traits specific to humans.

The researchers published their findings in the October 28, 2005, issue of the journal Public Library of Science Genetics (PLoS Genetics). The paper was published early online. Senior author Stephen W. Scherer is a HHMI international research scholar, a senior scientist in the Genetics and Genomic Biology Program at the Hospital for Sick Children in Toronto, Canada, and an associate professor of molecular and medical genetics at the University of Toronto.


This research expands on a Nature paper published on September 1, 2005, by HHMI investigator Evan E. Eichler at the University of Washington. Eichler’s group determined that novel duplications of genetic material within humans also significantly contribute to differences between the species.

Instead of identifying sequence changes between the two genomes at the base-pair level, Scherer focused his research on large structural variations in chromosomes between humans and chimps, specifically genetic inversions. Inversions can disrupt the expression of genes at the point where the chromosome breaks, as well as genes adjacent to breakpoints. "From a medical genetics perspective, there are probably hundreds of disease genes that have not yet been characterized," said Scherer. "The vast majority of disease gene discovery has been based on gene sequencing, but this is not a comprehensive view of chromosomes. We are using an evolutionary approach to identify mutations that may predispose people to disease."

According to Scherer, prior to this research, only nine inversions between humans and chimps had been identified. Using a computational approach, Scherer’s group identified 1,576 presumed inversions between the two species, 33 of which span regions larger than 100,000 base pairs--a sizeable chunk of DNA. The average human gene is smaller, only about 60,000 bases in length.

Scherer’s team experimentally confirmed 23 out of 27 inversions tested so far. Moreover, by comparing the chimp genome with its ancestor, the gorilla genome, they determined that more than half of the validated inversions flipped sometime during human evolution.

Perhaps even more interesting than the abundance of inversions that Scherer’s group unveiled was their discovery that a subset of the inversions are polymorphic--taking different forms--within humans, meaning that the human genome is still evolving. When the 23 experimentally confirmed inversions were tested against a panel of human samples, the scientists found three inversions with two alleles or pairs of genes displaying the human inversion in some people, whereas others had one allele of the human inverted sequence and one allele of the normal sequence in chimps.

Having one allele with an inversion and one allele without represents a ticking time bomb in genetic terms, Scherer said, since these alleles may improperly align and recombine during replication, ultimately causing DNA deletions or a loss of DNA that subsequent generations inherit. Scherer’s prior research on Williams-Beuren syndrome, a disease caused by DNA micro-deletions, identified a significantly higher incidence of inversions among the parents of afflicted patients.

Interestingly, one of the inversions that Scherer identified as polymorphic in his current paper includes a gene known to be involved in colorectal cancer. Whether individuals polymorphic for this inversion are at increased risk for the development of colorectal cancer is not yet known.

Scherer said that his group looked at only a very small subset of the human population when assessing the prevalence of polymorphisms. He suspects that polymorphisms, and structural variations in general, may be much more common than his preliminary analyses suggest.

"These findings may cause people to rethink their ideas about how species evolved," Scherer said. "They also highlight how the mechanisms of evolution may be associated with disease."

Scherer determined that about 10 percent of the presumed inversions either contain a complete gene within the flipped region, constitute a flipped region within a gene, or cause a breakpoint somewhere within a gene. These inversions represent prime targets for disease gene discovery, which Scherer’s team is exploring further.

Jennifer Donovan | EurekAlert!
Further information:
http://www.hhmi.org

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>