Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Identify Human DNA on the Fast Track

17.08.2006
Since completing the sequencing of the chimpanzee genome last year, geneticists have spent many hours comparing human DNA sequences to those of our closest evolutionary relative, looking for the differences that distinguish the two species. Now a team of researchers has found the human DNA sequence with the most dramatically increased rate of change.

The function of this region of DNA is still unknown, but it appears to be directly involved in the development of the human brain. “It's very exciting to use evolution to look at regions of our genome that haven't been explored yet,” said Howard Hughes Medical Institute investigator David Haussler, the leader of the team that included scientists from the University of California, Santa Cruz, the University of California, Davis, the University of Brussels, and Université Claude Bernard in France.

Their article will be published in an advance online publication on August 16, 2006, in the journal Nature.

Haussler's group found the DNA region using a technique developed by Katherine Pollard, a former postdoctoral fellow in Haussler's lab who is now an assistant professor at the University of California, Davis. Pollard compared the DNA sequences of chimps, mice, and rats to find the regions that had remained largely unchanged over the 80 million years or so since the common ancestor of those organisms. She then examined the same regions in humans to identify those that had changed markedly in the 6 million years since humans and chimps diverged from a common ancestor.

“Some DNA regions have hardly changed at all over many millions of years in most species,” said Pollard. “My twist was to look for the subset of these regions that have changed just in humans.”

Forty-nine regions, which the team called human accelerated regions (HARs), rose to the top of the list. Surprisingly, only two of these regions code for proteins. The majority of the regions tend to be located near genes that are involved in regulating the function of genes. Furthermore, 12 of the regions are adjacent to genes involved in the development of the brain.

The Nature paper looks in depth at the region that has undergone the most change in the human lineage, which the researchers called HAR1 (for human accelerated region 1). Only two of the region's 118 bases changed in the 310 million years separating the evolutionary lineages of the chicken and the chimp. Incredibly, since the human lineage separated from that of the chimp, 18 of the 118 nucleotides have changed. This region “stood out,” said Pollard.

But what does it do? To find out, Pollard began working with the wet lab, led by Sofie Salama. Haussler established the wet lab following his appointment as an HHMI investigator. After months of work, Salama and her lab mates determined that HAR1 is part of a larger DNA that is transcribed into RNA in the brain.

Then Salama got lucky. Pierre Vanderhaegen, a neuroscientist at the University of Brussels, was visiting Santa Cruz because he knew Salama's husband, who is also a neuroscientist. “I learned that Pierre was setting up to do in-situ hybridizations [at his lab in Brussels] to look at gene expression patterns in human embryonic brain samples,” said Salama. “So I gave him a DNA probe from the HAR1 region and said, `Try this.'”

A few months later Vanderhaegen e-mailed Salama with exciting news. He had discovered that RNA including the HAR1 region is first produced between the 7th and 9th weeks of gestation in human embryos. Furthermore, the RNA was produced by a Cajal-Retzius neuron, a particular type of cell that plays a critical role in creating the six layers of neurons in the human cortex.

Salama then determined that HAR1 actually lies in the region of overlap of two RNA genes that are transcribed in opposite directions along the DNA. Both genes appear to make RNAs that are not translated into proteins. The UC Santa Cruz team showed that these RNAs fold into particular shapes characterized by several helices. The changes to HAR1 during human evolution seem to have altered the length and configuration of some of these helices. “It's a brand new structure, unique,” said Salama. “The downside is that we don't have many good clues as to how it functions.”

Haussler's team is now following up on the clues that they do have. Other DNA regions produce stable RNA structures that have a variety of functions such as gene regulation or controlling the action of proteins. Furthermore, the same cells that express the HAR1 genes also produce a protein called reelin, which helps establish the architecture of the brain.

According to Haussler, the possibility that the HAR1 regions may play a role in the function of reelin is especially interesting since defects in reelin expression have been associated with schizophrenia and other mental disorders. “We still can't say much about the function [of the DNA containing HAR1],” said Haussler, “but it's a very exciting finding because it is expressed in cells that have a fundamental role in the design and development of the mammalian cortex.”

And beyond HAR1 lie HAR2, HAR3, and so on through the 49 regions Pollard identified with her DNA screen. “We've only studied one of these regions carefully,” said Haussler. “Now we have to go through the other 48.”

Jim Keeley | EurekAlert!
Further information:
http://www.hhmi.org

More articles from Life Sciences:

nachricht Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

nachricht First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>