Are 'orphaned genes' a thing?

A Reader Asks, "Are De Novo Genes Real?"
Ann Gauger 

We get good questions here at Evolution News. (Give us yours by hitting the orange Email Us button at the top of the page.) Today, a reader writes to ask, "Are de novo genes real?" This is a question that touches on a number of topics relevant to evolutionary biology, dealing with one of the most exciting aspects of genomic research today. So what are these things called de novo genes?

De novo genes are genes that are present in a particular species or taxonomic group, and not present in any others. Why are they there and where did they come from? To answer these questions we have to first deal with some important assumptions of evolutionary biology.

The first assumption is that sibling species are the product of descent with modification. The evidence cited in favor of this idea is that there is similarity of DNA sequence between sibling species, and that organisms can be grouped in nested hierarchies based on sequence comparisons. Now this hypothesis of common descent may be right. However, there are unresolved contradictions in the literature. So common descent is not unequivocally proven. De novo genes are one of those challenges to common descent. Let me explain why.

De novo genes, new genes present in one taxonomic group but not in others, are sometimes called orphan genes because they have no parent genes. They are also called taxonomically restricted genes (TRGs), because they may be shared by closely related species of the same taxon, but not others. What's a taxon? It's a level of classification, such as species, genus, family, order, class or phylum. Species of the same genus, for example, may share genes in common that are missing from all other species.

Because the field of research is still developing, different research groups use different criteria for deciding what counts as a TRG. For example, one recent estimate says that there are 634 genes that appear to have arisen de novo in the human genome, as compared with the chimpanzee and macaque genomes. But they counted RNA transcripts as genes, even if they have not yet been shown to code for protein. Another older estimate of over a thousand transcripts was finally reduced to a much lower number of de novo genes, because the researchers ruled out almost all of those candidate genes as non-protein coding. For a discussion about why this is, go here.

Despite these disagreements, de novo genes do exist. But when their origin -- where they came from -- is discussed, it reveals yet another assumption of evolutionary biologists. Evolutionists say, "Look, these orphan genes arose de novo. We can see how they might have been spliced together from similar DNA present elsewhere in the genome, or they might have come from non-coding DNA that has acquired a promoter or transcription factor binding site, and so is now expressed, and makes a functional protein, in the right place and at the right time."

These sentences reveal the second assumption -- that the existence of these new genes indicates there are natural processes to make them. After all, it must be possible to splice or activate new sequences to make TRGs, because there are TRGs.

That's an assumption of naturalism. The problem is there is no evidence to show that those proposed mechanisms actually work. There are no experiments that I know of to demonstrate that splicing yields functional products. Attempts in the lab show that splicing together even related protein domains yields non-functional products. Also, no one has shown that it is easy to acquire a promoter or transcription factor binding site so as to turn inactive, non-coding DNA into expressed, functional DNA. Getting a functional protein from random non-coding sequence is impossibly hard and would have to be demonstrated. If the function is regulating other genes via RNA, that would have to be proven to be feasible, too.

So do we know where TRGs came from? If no one tests how hard it is to splice together random sequence and get functional stuff, or how hard it is to acquire a new promoter, then we don't know whether de novo genes can be developed by evolutionary processes. If not, the alternative is shocking to evolutionary biologists -- perhaps, just perhaps they were made by a designer for that particular species or group. Perhaps the non-coding DNA was already ready to be functional, like an actor waiting in the wings for his cue, and was only activated in that one particular taxonomic group.

Bear in mind that TRGs can be up to 10-20 percent of a taxonomic group's genome, and may encode many of the special proteins unique to that taxonomic group. That's a huge chunk of DNA to arise by natural processes alone, and a big challenge for common descent. I am thinking of the phylum Cnidaria here. All Cnidaria (sea anemones, jelly fish, and Hydra for example) have tentacles with specialized cells called cnidocytes or nematocysts, which eject a little barbed tubule with a toxin into whatever touches them. They use these cells to capture and immobilize their prey. Many of the specialized proteins needed to make the nematocysts are TRGs specific to the phylum Cnidaria. Cnidaria are among the oldest of all extant phyla. Was their origin unique?

Take home lesson: Are de novo genes real? Yes. Do we know where they came from? No. Do they say something important about evolutionary processes? Indeed. But what they say remains to be seen.

Between physics and abiogenesis an unbridgeable chasm?

The Origin of Life, Self-Organization, and Information
Brian Miller

In an  article here yesterday, I described the thermodynamic challenges to any purely materialistic theory for the origin of life. Now, I will address one of the most popular and misunderstood claims that the first cell emerged through a process that demonstrated the property known as self-organization.

As I mentioned in the previous article, origin-of-life researchers often argue that life developed in an environment that was driven far from equilibrium, often referred to as a non-equilibrium dissipative system. In such systems, energy and/or mass constantly enters and leaves, and this flow spontaneously generates “order” such as the roll patterns in boiling water, the funnel of a tornado, or wave patterns in the Belousov-Zhabotinsky reaction. The assertion is that some analogous type of self-organizational process could have created the order in the first cell. Such claims sound reasonable at first, but they completely break down when the differences between self-organizational order and cellular order are examined in detail. Instead, the origin of life required complex cellular machinery and preexisting sources of information.

The main reason for the differences between self-organizational and cellular order is that the driving tendencies in non-equilibrium systems move in the opposite direction to what is needed for both the origin and maintenance of life. First, all realistic experiments on the genesis of life’s building blocks produce most of the needed molecules in very small concentrations, if at all. And, they are mixed together with  contaminants, which would hinder the next stages of cell formation. Nature would have needed to spontaneously concentrate and purify life’s precursors. However, the natural tendency would have been for them to diffuse and to mix with other chemicals, particularly in such environments as the bottom of the ocean.

Concentration of some of life’s precursors could have taken place in an evaporating pool, but the contamination problem would then become much worse since precursors would be greatly outnumbered by contaminants. Moreover, the next stages of forming a cell would require the concentrated chemicals to dissolve back into some larger body of water, since different precursors would have had to form in different locations with starkly different initial conditions. In  his  book on Origins, Robert Shapiro described these details in relation to the exquisite orchestration required to produce life.

In addition, many of life’s building blocks come in both right and left-handed versions, which are mirror opposites. Both forms are produced in all realistic experiments in equal proportions, but life can only use one of them: in today’s life, left-handed amino acids and right-handed sugars. The  origin of life would have required one form to become increasingly dominant, but nature would drive a mixture of the two forms toward equal percentages, the opposite direction. As a related but more general challenge, all spontaneous chemical reactions move downhill toward lower free energy. However, a large portion of the needed reactions in the origin and maintenance of life move uphill toward higher free energy. Even those that move downhill typically proceed too slowly to be useful. Nature would have had to reverse most of its natural tendencies in any scenario for extended periods of time. Scientists have never observed any such event at any time in the history of the universe.

These challenges taken together help clarify the dramatic differences between the two types of order:

Self-organizational processes create order (i.e. funnel cloud) at the macroscopic (visible) level, but they generate entropy at the microscopic level. In contrast, life requires the entropy at the cellular size scale to decrease.

Self-organizational patterns are driven by processes which move toward lower free energy. Many processes which generate cellular order move toward higher free energy.

Self-organizational order is dynamic — material is in motion and the patterns are changing over time. The cellular order is static — molecules are in fixed configurations, such as the sequence of nucleotides in DNA or the structure of cellular machines.

Self-organizational order is driven by natural laws. The order in cells represents specified complexity — molecules take on highly improbable arrangements which are not the product of natural processes but instead are arranged to achieve functional goals.

These differences demonstrate that self-organizational processes could not have produced the order in the first cell. Instead, cellular order required molecular machinery to process energy from outside sources and to store it in easily accessible repositories. And, it needed information to direct the use of that energy toward properly organizing and maintaining the cell.

A simple analogy will demonstrate why machinery and information were essential. Scientists often claim that any ancient energy source could have provided the needed free energy to generate life. However, this claim is like a couple returning home from a long vacation to find that their children left their house in complete disarray, with clothes on the floor, unwashed dishes in the sink, and papers scattered across all of the desks. The couple recently heard an origin-of-life researcher claim that order could be produced for free from any generic source of energy. Based on this idea, they pour gasoline on their furniture and then set it on fire. They assume that the energy released from the fire will organize their house. However, they soon realize that unprocessed energy creates an even greater mess.

Based on this experience, the couple instead purchase a solar powered robot. The solar cells process the energy from the sun and convert it into useful work. But, to the couple’s disappointment the robot then starts throwing objects in all directions. They look more closely at the owner’s manual and realize they need to program the robot with instructions on how to perform the desired tasks to properly clean up the house.

In the same way, the simplest cell required machinery, such as some ancient equivalent to ATP synthase or chloroplasts, to process basic chemicals or sunlight. It also needed proteins with the proper information contained in their amino acid sequences to fold into other essential cellular structures, such as portals in the cell membrane. And, it needed proteins with the proper sequences to fold into enzymes to drive the metabolism. A key role of the enzymes is to  link reactions moving toward lower free energy (e.g. ATP → ADP + P) to reactions, such as combining amino acids into long chains, which go uphill. The energy from the former can then be used to drive the latter, since the net change in free energy is negative. The free-energy barrier is thus overcome.

However, the energy-processing machinery and information-rich proteins were still not enough. Proteins eventually break down, and they cannot self-replicate. Additional machinery was also needed to constantly produce new protein replacements. Also, the proteins’ sequence information had to have been stored in DNA using some  genetic code, where each amino acid was represented by a series of three nucleotides know as a codon in the same way English letters are represented in Morse Code by dots and dashes. However,  no identifiable physical connection exists between individual amino acids and their respective codons. In particular, no amino acid (e.g., valine) is much more strongly attracted to any particular codon (e.g., GTT) than to any other.  Without such a physical connection, no purely materialistic process could plausibly explain how amino acid sequences were encoded into DNA. Therefore, the same information in proteins and in DNA must have been encoded separately.

In addition, the information in  DNA is decoded back into proteins  through the use of ribosomes, tRNAs, and special enzymes called aminoacyl tRNA sythetases (aaRS). The aaRSs bind the correct amino acids to the correct tRNAs associated with the correct codons, so these enzymes contain the decoding key in their 3D structures. All life uses this same process, so the first cell almost certainly functioned similarly. However, no possible connection could exist between the encoding and the decoding processes, since the aaRSs’ structures are a result of their amino acid sequences, which happen to be part of the information encoded in the DNA. Therefore, the decoding had to have developed independently of the encoding, but they had to use the same code. And, they had to originate at the same time, since each is useless without the other.

All of these facts indicate that the code and the sequence information in proteins/DNA preexisted the original cell. And, the only place that they could exist outside of a physical medium is in a mind, which points to design.