'smORFs': Functional Little Genome Gems Confront Evolution
by Jeffrey Tomkins, Ph.D. *
Until recently, thousands of tiny, potential protein-coding regions in the genome called "small open reading frames" or "smORFs" have been difficult to identify. They are now getting well-deserved attention for the important biochemical functions they play in the cell—like making your heart beat.1
In the present study published in Science, researchers found two smORF-encoded proteins in fruit fly genomes that were 28 to 29 amino acids in length and involved in regulating calcium transport and calcium intake in muscle and heart cells.1 And based on these proteins' 3-D shape and function in flies, the researchers found two counterparts in humans, which they also characterized and found to be involved in calcium uptake and heart muscle function as well.
Based on their 3-D shape, the researchers claimed that the human smORF proteins evolved from fly smORFs over a span of 550 million years, despite the fact that the DNA sequences that encode them showed virtually no similarity. The authors of the report revealed this contradiction burying it in the middle of their report where they said, "We searched for conservation of these smORFs in other species by using Basic Local Alignment Search Tool (BLAST) and only identified them in other Drosophilids [other fruit flies] (page 1118)."1 In other words, the DNA sequences for these smORFs were specific only to fruit flies and showed no evolutionary relationship to humans or any other creature. For all practical purposes, the evolutionary story behind this discovery was marginal all along.
Most of the proteins produced in the human genome are about 500 amino acids long on average. The proteins encoded by smORFs are only about 10 to 30 amino acids long and have been largely found by happenstance while studying gene mutations. Noted Harvard University physiologist, Alan Saghatelian (not an author on the current study) said, "These things have fallen through the cracks of traditional gene-finding algorithms, and most of the ones we know about have been serendipitously discovered."2
Interestingly, the smORF-related genes that contain segments that encode these small proteins—called long non-coding RNAs or lncRNAs—are often quite long (much like protein-coding genes), are complexly regulated, and highly multifunctional.1 These lncRNA genes occupy the regions of the genome once thought to be nothing but junk DNA. However, lncRNAs have been found to be highly cell and tissue specific in their function and also encode other important regulatory molecules like micro RNAs. Some lncRNAs also combine with various proteins to make different types of important cell machinery and are key players in epigenetic modifications (chemical tagging) in controlling the genome's function.3 Amazingly, lncRNAs are also proving to be key players in DNA repair, 3-D chromosomal positioning in the nucleus, and overall genome stability and function.4
Since no real DNA sequence-based evolutionary relationships exist for these human and fruit fly smORFs encoded within lncRNA genes, the most important news about this discovery is the continuing revelation of pervasive design and function in the genome—further negating the weak evolutionary paradigm of junk DNA.
- Magny, E. et al. 2013. Conserved Regulation of Cardiac Calcium Uptake by Peptides Encoded in Small Open Reading Frames. Science. 341 (6150): 1116-1120.
- Yong, E. Hidden Treasures. The Scientist. Posted on the-scientist.com August 22, 2013, accessed September 20, 2013.
- Rinn, J. L. and H. Y. Chang. 2012. Genome Regulation by Long Noncoding RNAs. Annual Review Biochemistry. 81:145–166.
- Ohsawa, R. J. H. Seol, and J. K. Tyler. 2013. At the intersection of non-coding transcription, DNA repair, chromatin structure, and cellular senescence. Frontiers in Genetics. 4 (36). doi:10.3389/fgene.2013.00136.
*Dr. Tomkins is Research Associate at the Institute for Creation Research and received his Ph.D. in genetics from Clemson University.
Article posted on October 14, 2013.