Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2023.06.14.545040

A generalized approach to genetic drift and its applications -- I. An example of the evolution of ribosomal RNA genes

Wang, X.·Ruan, Y.·Zhang, L.·Chen, X.·Shi, Z.·Wen, H.·Wu, C.-I.
View original source ↗Export metadata ↓

Abstract

Multi-copy gene systems that evolve within, as well as between, individuals are common. They include viruses, mitochondrial DNAs, multi-gene families etc. The paradox is that neutral evolution in two stages should be slower than single-copy systems but the opposite is often true. We now apply the Haldane model, recently generalized as the GH model (1), to quantify genetic drift in mammalian ribosomal RNA genes (rDNAs). On average, the copy number (C) is 150 - 300 per haploid. A neutral mutation in rDNA should take 4NC* generations to become fixed (N, the population size; C *, the effective copy number within individuals). While C > C* >> 1 is expected, the observed fixation time in mouse is < 4N, leading to the paradox of C* < 1. Genetic drift of rRNA genes thus appears 10-100 times stronger than in single-copy genes. The large increases are driven by a host of molecular mechanisms such as gene conversion and unequal crossover. Although each mechanism of drift is very difficult to quantify, the GH model permits the estimation of their total effects that constitute the aggregate "evolutionary noises". In humans, the fixation rate of rRNA genes is higher than the theoretical maximum of drift, hence, justifying the inference of adaptive evolution. In conclusion, the stochastic evolution in multi-copy gene systems, including viruses and others, can be effectively tracked by GH model.

Explore related subjects

evolutionary biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Wang, X., Ruan, Y., Zhang, L., Chen, X., Shi, Z., Wen, H., Wu, C.-I.. 2023-06-15. A generalized approach to genetic drift and its applications -- I. An example of the evolution of ribosomal RNA genes. https://doi.org/10.1101/2023.06.14.545040

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Denisovan introgression left differential selection regimes in Humans and Neanderthals on the SLC30A9 gene

Signals of positive selection around the SLC30A9 gene have been reported in human populations outside Africa. Selection likely acted on a highly differentiated single-nucleotide polymorphism, rs1047626, leading to a non-synonymous substitution in the encoded zinc transporter. Because of the striking similarity between the putatively selected SLC30A9 haplotype observed in several current human populations and the Denisovan individual, previous work has proposed adaptive introgression. Yet alternative explanations, including ancient human variation, and the precise archaic source -Neanderthal or Denisovan- remained unresolved. Considering the potentially complex evolution of SLC30A9, we applied Approximate Bayesian Computation (ABC) algorithms coupled to machine learning to investigate the most plausible evolutionary origin of this substitution. After modelling different evolutionary scenarios with forward-in-time simulations, our results highlight that the most probable scenario is a Denisovan origin of the rs1047626 polymorphism. However, the allele likely introgressed into Neanderthals first and was then passed into non-African modern humans. Moreover, the derived allele frequency for rs1047626 across several African populations is consistent with back-to-Africa migrations. Finally, our ABC analyses indicate strong positive selection in East Asian populations and other out-of-Africa populations, whereas in Neanderthal populations, the selection coefficient was probably neutral or slightly deleterious.

evolutionary biology↗
bioRxiv2026

RELAX does not reproduce its own estimates at default settings, and its output does not show it

Selection-intensity estimates from RELAX are reported as a point value of K with a likelihood-ratio P. We report that, at default settings and on data of ordinary size, the program does not reproduce its own fits. Of 27 enzyme entries refitted under two optimiser configurations, none reproduced its log-likelihood to within 0.01 units; the median change was 103 units, the largest over 3,400, and four verdicts reversed. Eighty null orthologues reproduced none. A byte-identical command returned a distinct likelihood on every repetition, single-threaded, across three releases, and on alignments simulated under the fitted model, where 3.3 per cent of replicates reproduced. The documented random-number seed never reaches the generator when assigned on the command line, yet reads back as the value supplied. PAML localises the cause: its two-ratio model, without site classes, reproduced its log-likelihood for all 288 genes; its site-class models agreed for 27 to 67 per cent. The instability follows the mixture over sites, not the program. The output does not show it: 46 of 410 fits ended with a negative likelihood-ratio statistic, impossible under convergence, and 123 of 410 report a K re-estimated under a domain restriction rather than the unconstrained maximum. Of 234 published studies using RELAX, none reported a seed. Seeding while holding the thread count at one reproduced sixty of sixty runs on twenty genes under two releases; the seed alone reproduced none of five, and no documentation states the second condition. We recommend that fits be repeated and their dispersion published.

evolutionary biology↗
bioRxiv2026

Sequential accumulation of adaptive alleles forms an inversion supergene in deer mice

Supergenes are clusters of co-inherited loci that affect multiple or complex phenotypes. Despite the growing number of chromosomal inversions identified as supergenes in natural populations, their molecular basis and evolutionary history often remain obscure. Here, we identified two candidate genes, Slc45a2 and Npr3, within a 41-Mb inversion supergene in the deer mouse (Peromyscus maniculatus) that respectively drive darker coats and longer tails - two traits associated with forest adaptation. Mice homozygous for the inversion (inv/inv) exhibit elevated Slc45a2 expression in melanocytes relative to the congenic standard genotype (std/std), disrupting pheomelanin production. In parallel, downregulation of Npr3 in inv/inv mouse growth plates prolongs postnatal growth of caudal vertebrae, resulting in tail elongation. Population-level analyses further implicate that this supergene arose through the subsequent accumulation of the Npr3 allele within the inversion, rather than by capturing all beneficial mutations at its origin.

evolutionary biology↗