21 Feb 2005: Duplication Makes A New Primate Gene What'sNEW

Next the biologists looked at other primates to reconstruct the more recent history of RGP. They write, "Although it is not possible to assess the temporal order of the events, the ancestor locus underwent duplication, inversion, partial deletion of the long RanBP2 exon 20, and acquisition of the 3'-end of the GCC2 gene coding for the GRIP domain.... The resulting progenitor locus contains the core coding and noncoding regions common to all the duplicated copies." At least some of the later duplications apparently occurred before the evolutionary split between the human and chimp lineages. Furthermore, "positive selection is acting on the first 20 exons of the RGP genes." That is, nucleotides which would code for different amino acids are substituted more frequently than synonymous nucleotides. The account seems well supported, and is consistent with other recent accounts for new genes.

We would like to ask how this reconstruction fits with the mainstream darwin theory of evolution and with our amended version, cosmic ancestry. In the latter, new genetic programs must first be installed by gene transfer. That source looks likely here, because the main progenitor gene, RANBP2, has no obvious ancestors. Rather, it is entirely absent in earlier-diverging eukaryotes like plants and fungi. Next, imported programs must be pieced together by a sophisticated software management system, as this story seems to illustrate. And the programs must then be optimized, as in the "positive selection" observed here. This process would also depend on sophisticated software management that can recognize an installed program. If the components of a genetic program may serve in more than one function, as in this example, we are not surprised. In sum, the processes described above may have merely reassembled and optimized a genetic program that already existed.

For the strictly darwinian interpretation of the history of RGP, we have questions. When point mutations were thought to be the primary source for new programs, it was at least possible to imagine stepwise paths, guided by natural selection, leading to new functions. But if wholesale recombinations of exon- and larger-sized sequences can write programs that never existed before, the first steps must be entirely hit-or-miss. How does the process find the right recombinations? How large is the sequence space of all possible recombinations? How many trials would be required? We are suspicious of the mathematics behind blind recombinations in a strictly darwinian world.

Next, when it is time for optimization within a narower range, we do not doubt the efficacy of natural selection acting on genes that have undergone "directed mutation." This seems to be the engine behind "positive selection." But without a powerful software management system, how is the darwinian genome able to preferentially substitute for the adaptive nucletides, and not the synonymous or essential ones? Under the darwinian philosophy, this phenomenon seems teleological.

For a question we have asked before, can recombination, mutation and darwinian natural selection write new programs without limit, as the history of life on Earth would seem to require? If so, closed system experiments, in biology or computer models, should be able to demonstrate that capability. To date, those experiments encounter a very near limit. We think those experimental results may reveal a basic fact about our world. But if the experimental environment is open to new programs supplied from elsewhere, obviously the original inventory of programs can expand as long as the external supply lasts.

In conclusion, the evidence concerning this new primate gene does not demonstrate that darwinian evolution can produce new genetic programs. Rather, it may demonstrate how pre-existing programs acquired in an open system are assembled and optimized.

What'sNEW

Alexander DeLuna et al., "Exposing the fitness contribution of duplicated genes" [

abstract], doi:10.1038/ng.123, p 676-681 v 40, Nature Genetics, online 13 Apr 2008. "These results suggest that most metabolic functions encoded by WGD genes are important today and were also important at the time of duplication."
Steffen Beisswanger and Wolfgang Stephan, "Evidence that strong positive selection drives neofunctionalization in the tandemly duplicated polyhomeotic genes in Drosophila" [abstract], 10.1073/pnas.0710892105, p 5447-5452 v 105, Proc. Natl. Acad. Sci. USA, 8 Apr (online 1 Apr) 2008. "Our results suggest that neofunctionalization has been achieved ...through the action of strong positive selection and the inactivation of gene conversion in part of the gene."
20 Oct 2007: New genetic functions arise when selection is imposed on a minor side function of a preexisting gene.
26 Sep 2007: The genomes of 17 species of fungi have been analysed to reconstruct gene duplication....
Jakob Lewin Rukov, Manuel Irimia et al., "High Qualitative and Quantitative Conservation of Alternative Splicing in Caenorhabditis elegans and Caenorhabditis briggsae" [abstract], 10.1093/molbev/msm023, p 909-917 v 24, Molecular Biology and Evolution, Apr (online 1 Feb) 2007. "...Gene duplication may be the major evolutionary mechanism for the origin of novel transcripts in these 2 species."
Eduard D. Akhunov et al., "Mechanisms and Rates of Birth and Death of Dispersed Duplicated Genes during the Evolution of a Multigene Family in Diploid and Tetraploid Wheats" [abstract], 10.1093/molbev/msl183, p 539-550 v 24, Molecular Biology and Evolution, Feb 2007 (online 29 Nov 2006). "Strong purifying selection acting on the ancestral gene ...was undiminished by the evolution of duplicated genes."
5 Dec 2006: Almost all human genes contain duplicated sequences.
Vaishali Katju and Michael Lynch, "On the Formation of Novel Genes by Duplication in the Caenorhabditis elegans Genome" [abstract], 10.1093/molbev/msj114, p 1056-1067 v 23, Molecular Biology and Evolution, May (online 24 Feb) 2006. "...More than 50% of newborn duplicates in Caenorhabditis elegans had unique exons in one or both members of a duplicate pair, indicating that many duplicates are not functionally identical to the progenitor copy at birth."
Brad A. Chapman et al., "Buffering of crucial functions by paleologous duplicated genes may contribute cyclicality to angiosperm genome duplication" [abstract], doi: 10.1073/pnas.0507782103, Proc. Natl. Acad. Sci. USA, online 8 Feb 2006. "Contrary to classical predictions that duplicated genes may be relatively free to acquire unique functionality, we find ...that SNPs encode less radical amino acid changes in genes for which there exists a duplicated copy at a 'paleologous' locus than in 'singleton' genes. Preferential retention of duplicated genes encoding long complex proteins and their unexpectedly slow divergence ...suggest that a primary advantage of retaining duplicated paleologs may be the buffering of crucial functions."
30 Sep 2005: The chimp genome has been sequenced. At least seventeen human genes contain exons missing in chimps.
Lars Kuepfer et al., "Metabolic functions of duplicate genes in Saccharomyces cerevisiae" [abstract], doi: 10.1101/gr.3992505, p 1421-1430 v 15, Genome Research, Oct 2005. "Thus, at least for metabolism, persistence of the paralog fraction in the genome can be better explained with an array of different, often overlapping functional roles."
27 Jun 2005: "Gene duplication is the primary source of new genes."
28 Feb 2005: Can pre-existing genetic programs be pieced together?
21 Feb 2005: Duplication Makes A New Primate Gene — our announcement of this new page.
17 Jan 2003: Duplicated genes serve backup functions.

References

1. Francesca D. Ciccarelli et al., "Complex genomic rearrangements lead to novel primate gene function" [abstract], DOI: 10.1101/gr.3266405, Genome Research, online 14 Feb 2005. Also see: Scientists Document Complex Genomic Events Leading To The Birth Of New Genes, ScienceDaily, 15 Feb 2005.