Evolutionary comparison finds new human genes

Nov 16, 2007
Over millions of years of evolution, a gene called GRIA2 has continued to do it's job of making a receptor for neurotransmitters. The portions of the gene that code for amino acids that make up a protein change in different ways from other parts of the genome, so computer algorithms can use these distinctive patterns of evolutionary change to identify new genes that have been missed by other methods. A portion of GRIA2 is shown here in an alignment of the genomes of several species, beneath a graph of the computer analysis. Peaks in the graph identify exons (regions that are expressed), separated by introns (non-coding regions). When a cell reads the gene to make a protein the introns are edited out. Credit: Provided/Siepel

Using supercomputers to compare portions of the human genome with those of other mammals, researchers at Cornell have discovered some 300 previously unidentified human genes, and found extensions of several hundred genes already known.

The discovery is based on the idea that as organisms evolve, sections of genetic code that do something useful for the organism change in different ways.

The research is reported by Adam Siepel, Cornell assistant professor of biological statistics and computational biology, Cornell postdoctoral researcher Brona Brejova and colleagues at several other institutions in the online version of the journal Genome Research, and it will appear in the December print edition.

The complete human genome was sequenced several years ago, but that simply means that the order of the 3 billion or so chemical units, called bases, that make up the genetic code is known. What remains is the identification of the exact location of all the short sections that code for proteins or perform regulatory or other functions.

More than 20,000 protein-coding genes have been identified, so the Cornell contribution, while significant, doesn't dramatically change the number of known genes. What's important, the researchers say, is that their discovery shows there still could be many more genes that have been missed using current biological methods. These methods are very effective at finding genes that are widely expressed but may miss those that are expressed only in certain tissues or at early stages of embryonic development, Siepel said.

"What's exciting is using evolution to identify these genes," Siepel said. "Evolution has been doing this experiment for millions of years. The computer is our microscope to observe the results."

Four different bases -- commonly referred to by the letters G, C, A and T -- make up DNA. Three bases in a row can code for an amino acid (the building blocks of proteins), and a string of these three-letter codes can be a gene, coding for a string of amino acids that a cell can make into a protein.

Siepel and colleagues set out to find genes that have been "conserved" -- that are fundamental to all life and that have stayed the same, or nearly so, over millions of years of evolution.

The researchers started with "alignments" discovered by other workers -- stretches up to several thousand bases long that are mostly alike across two or more species. Using large-scale computer clusters, including an 850-node cluster at the Cornell Center for Advanced Computing, the researchers ran three different algorithms, or computing designs -- one of which Siepel created -- to compare these alignments between human, mouse, rat and chicken in various combinations.

Over millions of years, individual bases can be swapped -- C to G, T to A, for example -- by damage or miscopying. Changes that alter the structure of a protein can kill the organism or send it down a dead-end evolutionary path. But conserved genes contain only minor changes that leave the protein able to do its job. The computer looked for regions with those sorts of changes by creating a mathematical model of how the gene might have changed, then looking for matches to this model.

After eliminating predictions that matched already known genes, the researchers tested the remainder in the laboratory, proving that many of the genes could in fact be found in samples of human tissue and could code for proteins. The researchers were sometimes able to identify the proteins by comparison with databases of known proteins. The discovered genes mainly have to do with motor activity, cell adhesion, connective tissue and central nervous system development, functions that might be expected to be common to many different creatures.

The entire project, from building and testing the mathematical models to running final laboratory tests, took about three years, Siepel said. The work was supported by the National Cancer Institute, a National Science Foundation Early Career Development Grant and a University of California graduate research fellowship.

Source: Cornell University

Explore further: Why do snakes flick their tongues?

add to favorites email to friend print save as pdf

Related Stories

Findings may advance iron-rich, cadmium-free crops

May 29, 2014

With news reports of toxic cadmium-tainted rice in China, a new study describes a protein that transports metals in Arabidopsis plants and holds promise for developing iron-rich but cadmium-free crops.

Algal genes may boost efficiency, yield in staple crops

May 19, 2014

(Phys.org) —As humanity faces more mouths to feed thanks to a swelling global population, new research has taken a step toward employing genes from blue-green algae to improve staple crop photosynthesis ...

UV-B light zaps cucumber disease

May 07, 2014

(Phys.org) —A collaborative project by Cornell researchers and colleagues in Norway has literally shed light on a perplexing pathogen problem by harnessing the power of the sun.

Famine fear won't sway minds on GM crops

May 02, 2014

A sack-hauling time traveler from the 21st century lands in an Irish potato field in 1849, just before a terrible famine, and asks: If you thought genetically modified (GM) potatoes could avert late blight disease, spare ...

Aluminum tolerance fix could open arable land

Apr 30, 2014

(Phys.org) —With as much as 40 percent of the world's potentially arable land unusable due to aluminum toxicity, a solution may be near: Cornell agricultural scientists report that a gene – and the protein ...

New alfalfa variety resists ravenous local pest

Apr 23, 2014

(Phys.org) —Cornell plant breeders have released a new alfalfa variety with some resistance against the alfalfa snout beetle, which has ravaged alfalfa fields in nine northern New York counties and across ...

Recommended for you

Why do snakes flick their tongues?

1 hour ago

Many people think a snake's forked tongue is creepy. Every so often, the snake waves it around rapidly, then retracts it. Theories explaining the forked tongues of snakes have been around for thousands of ...

Boat noise impacts development and survival of sea hares

1 hour ago

While previous studies have shown that marine noise can affect animal movement and communication, with unknown ecological consequences, scientists from the Universities of Bristol and Exeter and the École Pratique des Hautes ...

User comments : 2

Adjust slider to filter visible comments by rank

Display comments: newest first

docatomic
1 / 5 (1) Nov 17, 2007
It would be interesting to sequence some DNA from human remains of some centuries ago, in order to run the comparison again. Would this action provide sufficient proof of human evolution to finally dispell the myths of the Creationists? I personally doubt it would - yet I would surely wish to see some of the arguements they may attempt to pose as "counter-proofs"! ;-))
HeRoze
not rated yet Mar 31, 2008
What makes you think creationists don't believe in evolution within a species?