The prevailing wisdom in the field of molecular evolution was that new genes could only evolve from duplicated or rearranged versions of preexisting genes. It seemed highly unlikely that evolutionary processes could produce a functional protein-coding gene from what was once inactive DNA.
However, recent evidence suggests that this phenomenon does in fact occur. Researchers have found genes that arose from non-coding DNA in flies, yeast, and primates. No such genes had been found to be unique to humans until now, and the discovery raises fascinating questions about how these genes might make us different from other primates.
In this work, David Knowles and Aoife McLysaght of the Smurfit Institute of Genetics at Trinity College Dublin undertook the painstaking task of finding protein-coding genes in the human genome that are absent from the chimp genome. Once they had performed a rigorous search and systematically ruled out false results, their list of candidate genes was trimmed down to just three. Then came the next challenge. "We needed to demonstrate that the DNA in human is really active as a gene," said McLysaght.
The authors gathered evidence from other studies that these three genes are actively transcribed and translated into proteins, but furthermore, they needed to show that the corresponding DNA sequences in other primates are inactive. They found that these DNA sequences in several species of apes and monkeys contained differences that would likely disable a protein-coding gene, suggesting that these genes were inactive in the ancestral primate.
The authors also note that because of the strict set of filters employed, only about 20% of human genes were amenable to analysis. Therefore they estimate there may be approximately 18 human-specific genes that have arisen from non-coding DNA during human evolution.
This discovery of novel protein-coding genes in humans is a significant finding, but raises a bigger question: What are the proteins encoded by these genes doing? "They are unlike any other human genes and have the potential to have a profound impact," McLysaght noted. While these genes have not been characterized yet and their functions remain unknown, McLysaght added that it is tempting to speculate that human-specific genes are important for human-specific traits.
Scientists from the Smurfit Institute of Genetics, Trinity College Dublin (Dublin, Ireland) contributed to this study.
This work was supported by a President of Ireland Young Researcher Award from Science Foundation Ireland.
Aoife McLysaght, Ph.D. (email@example.com, +353-1-8963161 [office] or +353-86-1725488 [mobile]) has agreed to be contacted for more information.
Interested reporters may obtain copies of the manuscript from Peggy Calicchia, Editorial Secretary, Genome Research (firstname.lastname@example.org; +1-516-422-4012).
About the article:
The manuscript will be published online ahead of print on September 2, 2009. Its full citation is as follows: Knowles DG, McLysaght A. Recent de novo origin of human protein-coding genes. Genome Res doi:10.1101/gr.095026.109.
About Genome Research:
Launched in 1995, Genome Research (www.genome.org) is an international, continuously published, peer-reviewed journal that focuses on research that provides novel insights into the genome biology of all organisms, including advances in genomic medicine. Among the topics considered by the journal are genome structure and function, comparative genomics, molecular evolution, genome-scale quantitative and population genetics, proteomics, epigenomics, and systems biology. The journal also features exciting gene discoveries and reports of cutting-edge computational biology and high-throughput methodologies.
About Cold Spring Harbor Laboratory Press:
Cold Spring Harbor Laboratory is a private, nonprofit institution in New York that conducts research in cancer and other life sciences and has a variety of educational programs. Its Press, originating in 1933, is the largest of the Laboratory's five education divisions and is a publisher of books, journals, and electronic media for scientists, students, and the general public.
Genome Research issues press releases to highlight significant research studies that are published in the journal.
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