Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2023.08.07.552269

Purifying selection and adaptive evolution proximate to the zoonosis of SARS-CoV-1 and SARS-CoV-2

Townsend, J. P.·Gaughran, S.·Hassler, H. B.·Fisk, J. N.·Nagib, M.·Wu, Y.·Wang, Y.·Wang, Z.·Galvani, A. P.·Dornburg, A.
View original source ↗Export metadata ↓

Abstract

Over the past two decades the pace of spillovers from animal viruses to humans has accelerated, with COVID-19 becoming the most deadly zoonotic disease in living memory. Prior to zoonosis, it is conceivable that the virus might largely be subjected to purifying selection, requiring no additional selective changes for successful zoonotic transmission. Alternatively, selective changes occurring in the reservoir species may coincidentally preadapt the virus for human-to-human transmission, facilitating spread upon cross-species exposure. Here we quantify changes in the genomes of SARS-CoV-2 and SARS-CoV-1 proximate to zoonosis to evaluate the selection pressures acting on the viruses. Application of molecular-evolutionary and population-genetic approaches to quantify site-specific selection within both SARS-CoV genomes revealed strong purifying selection across many genes at the time of zoonosis. Even in the viral surface-protein Spike that has been fast-evolving in humans, there is little evidence of positive selection proximate to zoonosis. Nevertheless, in SARS-CoV-2, NSP12, a core protein for viral replication, exhibited a region under adaptive selection proximate to zoonosis. Furthermore, in both SARS-CoV-1 and SARS-CoV-2, regions of adaptive selection proximate to zoonosis were found in ORF7a, a putative Major Histocompatibility Complex modulatory gene. These findings suggest that these replication and immunomodulatory proteins have played a previously underappreciated role in the adaptation of SARS coronaviruses to human hosts.

Explore related subjects

evolutionary biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Townsend, J. P., Gaughran, S., Hassler, H. B., Fisk, J. N., Nagib, M., Wu, Y., Wang, Y., Wang, Z., Galvani, A. P., Dornburg, A.. 2023-08-07. Purifying selection and adaptive evolution proximate to the zoonosis of SARS-CoV-1 and SARS-CoV-2. https://doi.org/10.1101/2023.08.07.552269

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↗