So-called pseudogenes become unable to code for proteins at a certain point, and natural selection has been said in the past to acknowledge them. A new study reaffirms this notion but adds that natural selection influences said pseudogenes. The study was conducted by experts from Moscow State University out of the Faculty of Bioengineering and Bioinformatics, and it was published in Genome Biology and Evolution.
To this day, mind you, it remains a broadly embraced consensus that genes are the building blocks of life in much the same way that atoms are the building blocks of matter. In spite of this, both scientists and philosophers are coming to doubt how pertinent genes are to the holistic understanding of biology. In lieu of the centrality of genes to this subject for more than a hundred years now, the scientific community has never managed to reach a universally acceptable, unchanging definition of what a gene even is. They've always tried to correlate its working definitions with human characteristics being explained by genes, but there's never been any legitimate success in that regard.
The accepted comprehension of genes thus far has been, instead, in relation to how determinative they are of those characteristics, and even that hasn't been consistent on issues like hereditary diseases. This is why University of Exeter Professor Staffan Müeller-Wille and Max Planck Institute Emeritus Scientific Member for the History of Science Hans-Jörg Rheinberger have just written a new book, The Gene: From Genetics to Postgenomics, in which they analyze the inconsistencies of how genes have been understood over time. In the recent history, they focus at least in part on how technology has made it possible to sequence entire genomes in very short time and at very little cost. They also look at the study of biomolecular systems and the gradual evolution thereof.
"The most important insight associated with the discovery of the gene in the early 20th century was that the order in which genes operate does not reflect the order in which the human (or plant or animal) body develops," write Müeller-Wille and Rheinberger for The Conversation in discussing the topics of the new text they've co-authored. "One gene is not linked to one physical trait — many genes control many traits. Likewise, a single trait is often controlled by hundred [sic] of genes forming complex networks of interaction."
The Moscow study looks just at natural selection's role in pseudogenes encoding proteins. There are times when protein plays a less significant role in the adaptation and survival of a living organism perhaps due to environmental changes for example. Regardless of the circumstances, whatever mutations occur in the gene coding for that specific protein suddenly become no longer germane to the functions of that organism overall. "Scientists have known for a long time that, after a gene undergoes a harmful mutation, e.g. a nonsense mutation, it stops working and turns into a pseudogene," according to Nadezhda Potapova, one of the Moscow study's co-authors and a postgraduate in the Faculty of Bioengineering and Bioinformatics.
"In this case, negative selection (the one that removes harmful mutations from the population) stops applying to it, and nonsynonymous mutations (the ones that cause the replacement of one amino acid in a protein with another) start to accumulate in the gene at the same speed as synonymous ones (the ones in which amino acids are not replaced)," Potapova adds. "Previously, this was indirectly referred to in many works with individual examples, but no full-scale research of the effect of nonsense mutations has been ever conducted before."
Now, a human genome consists of between 53 and 100 non-functioning alleles, and about 21-27 of those alleles were switched off specifically because of nonsense mutations. They're called nonsense mutations because they can deprive a gene of its purpose and function; it's a kind of mutation that yields terminating codon occurrence, and at terminating codons, protein synthesis just stops. Nonsense mutations can happen by way of insertions, replacements or even deletions of whole nucleic acid bases in the genetic code. It's the large number of alleles that involve nonsense mutations that made scientists consider the possibility that there might be more sense to this than we give these mutations credit for.
The research team studied Zambian population genomes from Drosophila melanogaster and found them to consist of 35 nonsense mutations on average. They focused on nonsense alleles that popped up due to the replacement of a single nucleotide. Their findings reveal that negative selection, which is the selective reduction of the rate at which a specific feature of the target population occurs) didn't impact those facets of the flies' coding genes, yet natural selection did to a minimal degree. They suspect this might have to do with alternative splicing, which is another way to read the same region of DNA by shifting the start and end points of the loci being read.
"We used Drosophila melanogaster genomes. Based on it, we managed to confirm that nonsense mutations actually switch off single exon genes (i.e. the genes that contain no introns cut out during protein synthesis), and they start to accumulate both synonymous and nonsynonymous mutations at the same speed. In multi-exon genes (genes with several introns) only the exon with the mutation seems to be left out, and the others remain under the influence of negative selection, though slightly weakened," Potapova explains.
[researchpaper 리서치페이퍼=Cedric Dent 기자]