The molecular evolution and popgen field is known to have the most mathematics among all branches of biology. But precisely because of that, it needs many simplifying assumptions or premises, which often lead to the fallacy of begging the question. I here gave a few examples regarding the concept of the mutation or genetic load and the genetic load argument for junk DNA, based on reading a paper on the genetic load (Lesecque et al 2012). Some have used the genetic load as the best argument for the junk DNA notion (Palazzo and Gregory, 2014; Graur, 2015). I also discuss the assumption of non-conservation equaling non function and the assumption of infinite sites.
Lesecque et al say: “The mutation load was more formally defined as the proportional reduction in mean fitness of a population relative to that of a mutation-free genotype, brought about by deleterious mutations (Crow 1970):
L = (Wmax - Wmean)/Wmax
where Wmean is the mean fitness of the population at equilibrium and Wmax is the mean fitness of a deleterious mutation-free individual.”
Is there a deleterious mutation-free individual in a real world or even an imagined world? All mutations, as random mistakes, have a deleterious aspect to an ordered system, if not individually, then collectively. Many mutations could be both deleterious and beneficial. For example, they could be beneficial to adaptive immunity that requires genome variation for producing diverse antibody responses but deleterious to innate immunity that requires conserved proteins to recognize conserved sequences shared by a certain class of microorganisms. By failing to recognize the both deleterious and beneficial nature of most mutations and by classifying mutations into two kinds (deleterious and non-deleterious with the latter consisted of mostly neutral ones), the assumption on the concept of deleterious and non-deleterious mutations eventually led to the genetic load argument for the conclusion that most mutations must be neutral. Here, one sees that the neutral conclusion is already embedded in the premise that led to it. The premise does not recognize the fact that most mutations appear neutral or nearly neutral as a result of balancing selection, and the fact that all mutations have a deleterious aspect as noises to a finely tuned system. Of course, that premise works for a junkyard like system.
Lesecque et al say: ““If the fitness effects of deleterious mutations are independent from one another, the mutation load across all loci subject to recurrent mutation is approximately
L = 1-e-U
(Kimura and Maruyama 1966), where U is the overall rate of deleterious mutation per diploid genome per generation. This simple formula is a classic result of evolutionary genetics.”
So, a classic formula for the genetic load argument is based on the assumption that the fitness effects of deleterious mutations are independent from one another. For a junk yard, yes, the consequences of errors in the building parts are independent from one another. However, for a system that is ordered and built by network-like interactions among the building parts, no, the consequences of errors in the building parts are NOT independent from one another. In fact, recent studies in genomics are constantly discovering epistatic interactions among mutations. So, here one sees clearly again, the neutral or junk DNA conclusion is already embedded in the premise that treats an organism more as a junkyard than a highly ordered system with components organized in a network fashion. When you have already assumed an organism to be junk like, why bother showing us the math formula and deduction leading to the junk DNA conclusion? You should just say that most DNAs are junks because I said so.
Finally, none of the premises related to the genetic load concept recognized the fact that a large collection of otherwise harmless mutations within an individual could be deleterious, as our recent papers have shown. Well, again, such a fact certainly does not exist for a junkyard-like system. By not recognizing that fact or being too naïve to see it, the practitioners in the popgen field have again and again assumed biological systems to be junk like before setting out to prove/deduce that they are made of largely junks.
I also briefly comment on a paper by the Ponting group concluding that human genome is only about 8% functional (Rands et al, 2014). The premise for that deduction is that non-conservation means non-function. Again, building parts for different junk yards are not conserved and nonfunctional. So, non-conservation means non function holds for junk yards. But for organisms relying on mutations to adapt to fast changing environments, recurrent or repeated mutations at the same sites at different time points in their life history are absolutely essential for their survival. Less conserved sequences are more important for adaptation to external environment, while the more conserved ones are important for internal integrity of a system. For bacteria or flu viruses to escape human immunity or medicines, the fast changing or non-conserved parts of their genome are absolutely essential. So, here again, by assuming non-function for the non-conserved parts of the genome, one is assuming an organism to be like a junk yard.
Other key assumptions like the infinite sites model (means neutral sites) are critical for phylogenetics as it is practiced today and for the absurd Out of Africa model of human origin that uses imagined bottlenecks to explain away the extremely low genetic diversity of humans. Well, a junk yard can certainly have an infinite number of parts and tolerate an infinite number of errors. An organism’s genome is finite in size and essentially nothing compared to infinite size. Within such finite size genomes, the proportion that can be free to change without consequences is even more limited or finite.
A paradigm shift (or revolutionary science) is, according to Thomas Kuhn, a change in the basic assumptions, or paradigms, within the ruling theory of science. The above analyses show that the assumptions for the popgen and molecular evolution field are largely out of touch with reality as more reality becomes known, and must be changed quickly if the field wants to avoid fading into oblivion and stay relevant to mainstream bench biology, genomic medicine, archeology, and paleontology. Those assumptions have produced few useful and definitive deductions that can be independently verified and avoid the fate of constant and endless revisions, like we have seen from 1987 to now for the Out of Africa model or the Neanderthals.
Lesecque Y, Keightley PD, Eyre-Walker A (2012) A resolution of the mutation load paradox in humans. Genetics 191: 1321–1330 .
Palazzo AF, Gregory TR (2014) The Case for Junk DNA. PLoS Genet 10(5): e1004351. doi:10.1371/journal.pgen.1004351
Dan Graur (2015) If @ENCODE_NIH is right each of us should have on average from 3 × 10^19 to 5 × 10^35 children. https://www.dropbox.com/s/4bj3andtlu3y9hk/Genetic%20mutational%20load.docx?dl=0 …
Rands CM, Meader S, Ponting CP, Lunter G (2014) 8.2% of the Human Genome Is Constrained: Variation in Rates of Turnover across Functional Element Classes in the Human Lineage. PLoS Genet 10(7): e1004525.