Evolutionary theory holds that all living things came about through random, natural processes. So conventional scientists believe the genome has developed through these means, and large sections of it have therefore been assumed to be nonfunctional. These alleged nonfunctional regions supposedly are a source of new gene evolution. But these evolutionary presuppositions of nonfunctionality are being challenged by an unexpected group—members of the biomedical genomics community.

These scientists, healthcare providers, industry professionals, and others are dedicated to studying the role of all parts of the genome in health and disease. Their practical focus on developing and improving diagnoses and treatments means they are freer to follow evidence where it leads. And that evidence doesn’t lead to evolution.

Background

The genome is the complete set of chromosomes in a cell. It’s like a computer hard drive that encodes critical information for growth, development, physiology, and adaptation. Protein-coding genes are DNA segments that carry instructions for making proteins. These segments are copied (transcribed) into RNA in a temporary fashion, just like copies of software programs are put into short-term memory on a computer.¹ These temporary RNA instructions are then used as templates to make proteins.

As genome research technologies became more advanced and comprehensive, scientists realized that protein-coding genes are only a small portion of the genome transcribed into RNA. In fact, researchers discovered that nearly the entire genome is transcribed. This is called pervasive transcription.^2,3 The initial and ongoing discovery of pervasive transcription has led some scientists to call the genome an “RNA machine.”³

One significantly large component of this transcriptional landscape is produced from long non-coding RNAs (lncRNA). This diverse class of genes doesn’t code for proteins but instead produces a variety of structural or functional RNAs typically longer than 200 bases. These lncRNA genes outnumber protein-coding genes by at least three to one and perform a wide variety of critical activities in the cell.^4,5

Figure 1. Diagram illustrating alternative splicing of an lncRNA gene

Because evolutionists didn’t understand lncRNA gene function in the early days of the human genome project, they originally and prematurely labeled these regions “junk DNA.” A wide variety of these genes have since been investigated and found to have important functions,^6–11 although it has been difficult to assign specific functions to many of the human lncRNAs.¹² As far as gene structure goes, lncRNAs have essentially the same exon-intron system that proteincoding genes have along with the same regulatory regions such as promoters and enhancers (Figure 1).¹³

On a historical note, the first nearly complete draft of the human genome was published about 20 years ago. The assessment of its information content attributed only a small percentage of the genome to protein-coding sequences (exons as represented in mRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), and introns from protein-coding genes.^14,8

As of 2023, the known landscape of the human genome had not changed much concerning these features, which make up about 25% of the genome. The overall information content, however, has been radically altered by the addition of numerous lncRNAs, which constitute about 75% of the genome (Figure 2).⁸ Numerically speaking, there are about 20,000 protein-coding genes and over 100,000 lncRNA genes in the human genome.⁶

Figure 2. A comparison of the known genomic landscape between 1980 and 2020. Image adapted from figure 1 in reference 8.

Role and Function of lncRNAs

The cell’s nucleus contains a greater proportion of lncRNAs than protein-coding mRNAs. The lncRNAs’ roles there are both functional and structural. Functionally, they are important for regulating gene transcription, stabilizing chromosomes, assisting in epigenetic modifications of both the DNA and histones, binding to certain proteins and acting as nuclear address delivery guides, and helping modify the three-dimensional structure of the genome. In fact, one interesting study showed that all the chromosomes of the human genome are literally painted with a specific class of repeat-rich lncRNAs. When these lncRNAs are eliminated with an enzyme called RNAse, the chromosomes literally collapse.¹⁵

Many studies show that lncRNAs participate in virtually all levels of chromosome organization and in defining cell type and structure, and they widely regulate gene expression. These functional roles are formed through RNA-RNA, RNA-DNA, and RNA-protein interactions. Regarding RNA-RNA interactions, lncRNAs form complex networks with both microRNAs¹⁶ and messenger RNAs in the nucleus and cytoplasm.^17,18 In the nucleus these three-way interaction networks regulate gene expression, and in the cytoplasm they regulate protein production (translation). One particularly interesting class of regulatory lncRNAs are those produced from the opposite DNA strand of a gene.¹⁹ Called antisense RNAs, they’re key to regulating the splicing of a newly copied RNA from a gene.

In the cell’s cytoplasm, lncRNA interactions are involved in protein production and the subsequent transport and localization of that protein to a specific location in the cell. While RNA editing primarily takes place in the nucleus of a cell via the aid of lncRNAs,²⁰ it can also take place within cytoplasm organelles like the mitochondria and chloroplasts (photosynthetic sites in plants).

Many lncRNAs are also involved in the regulation of cell differentiation and development in animals and plants. In mice, we now know that five different lncRNAs are involved in maintaining the proper amount of developmental and growth-related proteins in a process called dosage compensation.⁹ Several other lncRNAs have been shown to regulate mouse brain development, and others control limb development (one lncRNA), organism viability (seven lncRNAs), the immune system (six lncRNAs), fertility (one lncRNA), and overall chromosome stability (one lncRNA).

Brown mouse

Besides growth and development, lncRNAs also play a wide range of roles in mammals’ physiological processes.⁹ Some of these processes are involved in DNA damage control and repair, antibody diversity in immune cells, secretion by immune cells of specialized disease-fighting substances (cytokines), inflammation and neuropathic pain, cholesterol biosynthesis and homeostasis, growth hormone and prolactin production, glucose metabolism, cellular signal transduction and transport pathways, and brain cell synapse function. Research also shows lncRNAs are important for the structure and function of the cell membrane.⁹

Adaptation and lncRNAs

Fruit Flies

Cold tolerance is an important adaptive trait that allows creatures to inhabit a wide array of latitudes on a continent. The fruit fly (Drosophila melanogaster) is one of the most studied creatures in researching genetic mechanisms of adaptation. In a 2008 study, researchers captured hundreds of fruit flies on the east coast of Australia from 41 different locations along a latitudinal cline from 15° to 43°.²¹ The gene associated with heat tolerance that they targeted for analysis was hsr-omega, which encodes a large lncRNA. In fact, the gene itself encodes two different lncRNAs: omega-c operates in the cell cytoplasm, and omega-n stays in the nucleus.

Fruit flies (Drosophila melanogaster)

Additionally, the gene encodes a long series of tandem repeats where the repeated unit is 280 nucleotides long. The omega-n variant in the nucleus is the long version of the gene that includes the repeats. The omega-c variant is much shorter and excludes the long section of repeats. It only comprises the front section of the gene minus a small section.

As location shifts from north to south, the transcription of the hsr-omega gene as a whole decreases in response to latitude. The amount of repeats in the omega-n variant decreases in response to cold, and the quantity of the omega-n RNAs decreases. Finally, during fly recovery from cold exposure, there is a large increase of the omega-c variant in the cytoplasm.

Butterflies and Moths

Hawk moth

Variations in the wing pigmentation of butterflies and moths (lepidopteran insects) are striking examples of adaptation. They allow the insect to hide itself from predators by blending into its environment or even mimicking another creature’s appearance. In lepidopterans, there is a chromosomal region called the cortex locus, a complex segment containing multiple genes and regulatory elements that work together to control wing patterns.²² While the specific number of genes within the cortex locus varies depending on the kind of lepidopteran, the region is vital for understanding the genetic basis of wing pattern diversity in these insects.

A recent study revealed the pivotal role of an lncRNA gene transcribed from the cortex locus.²² Named ivory, the gene modulates and controls color patterning in butterflies and kicks in gear during pupal development in the cocoon, which is the metamorphosis stage of the lepidopteran. The gene is turned on after about 20% of pupal development and persists until about 60 hours after pupal formation stops. Overall, the data show that the ivory lncRNA gene functions as a master switch for color pattern specification, making it invaluable for adaptive diversification of wing patterns in butterflies and moths.

Plants

Grass

Since plants are sessile organisms and can’t move around, they need a robust molecular genetic toolkit to adapt to a wide variety of environmental challenges. lncRNA genes and their RNA products play an important role in this.²³ And because plants are more easily studied than animals due to fewer regulations and less required maintenance, lncRNA research in various grasses, herbaceous plants, vines, shrubs, and trees has exploded in the past 10 years.

These lncRNAs in plants are encoded in genes outside protein-coding genes, in the introns of protein-coding genes, on the opposite strand of protein-coding genes (producing antisense transcripts), and are even produced from the promoters of protein-coding genes. Their functions range from regulating gene transcription to regulating protein production, regulating epigenetic modifications, and modifying the genome’s 3-D structure.

The major environmental cues they respond to are cold, heat, salt stress, light, and water availability. They also help regulate plant growth and development by coordinating changes in plant hormones in response to all sorts of environmental stimuli. Nearly every aspect of plant adaptation and physiology involves the precise coordinated action of lncRNAs.

Conclusion

Biomedical researcher

In the evolutionary paradigm, the incredible complexity of the genome is believed to have somehow evolved by random processes. Much of it is therefore thought to be useless evolutionary junk. The leading proponents of evolution are steeped in this type of speculation, called theoretical evolution, and have tried to downplay recent discoveries of pervasive function across the genome, which is largely based on lncRNAs.

However, the biomedical genomics community is pragmatically focused on diagnosing and curing disease. As a result, biomedical researchers are not as limited by false evolutionary presuppositions and have associated lncRNAs with many different aspects of human health. Thanks to these efforts and the work of plant and animal researchers in adaptive systems, the incredible functionality of the entire genome and all of its seemingly infinite complex workings are glorifying the omnipotent Creator, the Lord Jesus Christ who made it all.

References

1. The beginning section of this article contains revised material from Tomkins, J. P. 2017. Pervasive Genome Function Debunks Junk DNA. Acts & Facts. 46 (5): 14.
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12. Even many protein-coding genes in humans still have unknown functions because of the ethical limitations of conducting research with human subjects. Human cells grown in the lab are commonly studied for RNA transcription from both protein and non-coding RNA genes, but they’re not necessarily indicative of what goes on inside a living human being.
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19. DNA is double-stranded with information running on both strands.
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