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18 Nov 2024
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Faster model-based estimation of ancestry proportions

fastmixture generates fast and accurate estimates of global ancestry proportions and ancestral allele frequencies

Recommended by ORCID_LOGO based on reviews by Oscar Lao Grueso and 2 anonymous reviewers

The estimation of ancestry proportions in individuals is an important analysis in both evolutionary biology and medical genetics. However, popular tools like ADMIXTURE (Alexander et al. 2009) and STRUCTURE (Pritchard et al. 2000) do not scale well with the large amount of data currently available. Recent alternative methods, such as SCOPE (Chiu et al. 2022), favour scalability over accuracy. 

In this study, Santander and coworkers introduce a new software, called fastmixture, which estimates ancestry proportions and ancestral allele frequencies using novel implementations for initialisation and convergence of its model-based algorithm (Santander et al. 2024). In simulated datasets, fastmixture displays desirable properties of speed and accuracy, with its performance surpassing commonly used software (Alexander et al. 2009, Pritchard et al. 2000, Chiu et al. 2022, Mantes et al. 2023). fastmixture is almost 30 times faster than ADMIXTURE under a complex model with five ancestral populations, while retaining similar accuracy levels. When applied to data from the 1000 Genomes Project (1000 Genomes Project Consortium 2025), fastmixture recapitulated expected levels of global ancestry. The new software is freely available on GitHub with an accessible documentation. fastmixture accepts input files in PLINK format.

It remains an open question whether extensive parameter tuning could increase the scalability and accuracy of established methods. A comprehensive assessment of fastmixture over a wide range of data processing options (Hemstrom et al. 2024) is also missing. Finally, whether model-based approaches are fully scalable to ever increasing biobank datasets is still under debate. Nevertheless, the superior computational performance of fastmixture is evident and it is likely that this new software will soon replace existing popular tools to estimate global ancestry proportions. 

References

Alexander DH, Novembre J, Lange K. Fast model-based estimation of ancestry in unrelated individuals. Genome Res. 2009;19(9):1655-1664.  https://doi.org/10.1101/gr.094052.109

Pritchard JK, Stephens M, Donnelly P. Inference of population structure using multilocus genotype data. Genetics. 2000;155(2):945-959.  https://doi.org/10.1093/genetics/155.2.945

Chiu AM, Molloy EK, Tan Z, Talwalkar A, Sankararaman S. Inferring population structure in biobank-scale genomic data. Am J Hum Genet. 2022;109(4):727-737.  https://doi.org/10.1016/j.ajhg.2022.02.015

Santander CG, Refoyo Martinez A, Meisner J. Faster model-based estimation of ancestry proportions. bioRxiv 2024; ver.2 peer-reviewed and recommended by PCI Evol Biol. https://doi.org/10.1101/2024.07.08.602454

Mantes AD, Montserrat DM, Bustamante CD, Giró-I-Nieto X, Ioannidis AG. Neural ADMIXTURE for rapid genomic clustering. Nat Comput Sci. 2023;3(7):621-629.  https://doi.org/10.1038/s43588-023-00482-7

1000 Genomes Project Consortium, Auton A, Brooks LD, et al. A global reference for human genetic variation. Nature. 2015;526(7571):68-74.  https://doi.org/10.1038/nature15393

Hemstrom W, Grummer JA, Luikart G, Christie MR. Next-generation data filtering in the genomics era. Nat Rev Genet. 2024;25(11):750-767.  https://doi.org/10.1038/s41576-024-00738-6

Faster model-based estimation of ancestry proportionsCindy G. Santander, Alba Refoyo Martinez, Jonas Meisner<p>Ancestry estimation from genotype data in unrelated individuals has become an essential tool in population and medical genetics to understand demographic population histories and to model or correct for population structure. The ADMIXTURE softw...Bioinformatics & Computational Biology, Human Evolution, Population Genetics / GenomicsMatteo Fumagalli2024-07-14 11:48:39 View
13 Mar 2025
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Unraveling genetic load dynamics during biological invasion: insights from two invasive insect species

The genetic load of invasive population: how little do we know ?

Recommended by ORCID_LOGO based on reviews by Sylvain Glémin and 2 anonymous reviewers

We live both in a worrying and fascinating time. Worrying because human-induced global change has dramatic consequences on biodiversity around the world. Fascinating because these changes enable us to witness evolutionary processes unfolding on relatively short time scales. One such process is biological invasion. An intriguing evolutionary question is to understand which factor facilitates the success of an invasive species. In particular, serial bottlenecks at the expanding front should reduce the effective population size and decrease genetic diversity. Theoretically, this will increase the fixation of deleterious mutations due to the effect of genetic drift and overall affect the evolutionary potential of the invading species. In the short term, reduced genetic diversity and inbreeding in small populations increases the number of recessive deleterious variants exposed in a homozygous state. This may generate a reduction in mean fitness of the population. However, in the long term and under specific demographic scenarios recessive deleterious alleles may be more efficiently removed by purifying selection. Such purging may explain the success of invasion by reducing inbreeding depression and minimizing loss of fitness. Here, Lombaert et al. estimate the genetic load in two invasive insect species, a predator species, the harlequin ladybird (Harmonia axyridis) and a crop pest species, the western corn rootworm (Diabrotica virgifera virgifera). 

The authors smartly took advantage of a pool-seq transcriptome-based exome capture method to estimate genetic load and assess the purge hypothesis using standard population genetic statistics, such as the ratio of nonsynonymous over synonymous expected heterozygosity, the frequency of derived alleles, and their excess or deficit.

The results revealed different patterns in the two species:

In the western corn rootworm, the authors find a clear signal of reduced genetic diversity in invasive populations. This was associated with a slightly reduced genetic load. However, there was only marginal evidence of purging regarding the most deleterious mutations, and in a single population, with moderately deleterious variants being weakly purged, as theoretically expected. 

In the harlequin ladybird, in contrast, the reduction of genetic diversity in invasive populations has been small, a result related to the mild severity of the bottlenecks. In this species, the authors found a tendency toward fixation of the genetic load and no signal of purging. 

Such results are intriguing, showing that different species seem to exhibit contrasted fate of genetic load. Differences in the invasion history and ecology of the species may explain these patterns. This is one of the first studies to use a population genomics approach to study the genetic load associated with biological invasion. Future studies based on whole genome data collected at the individual level across multiple species are needed to better understand the dynamics of genetic load during biological invasion and to draw more general conclusions. Advances in forward simulations may also be used to shed light on the evolution of the genetic load at different stages of the invasion process and under different strengths of bottlenecks.

 

References

Eric Lombaert, Aurelie Blin, Barbara Porro, Thomas Guillemaud, Julio S Bernal, Gary Chang, Natalia Kirichenko, Thomas W Sappington, Stefan Toepfer, Emeline Deleury (2025) Unraveling genetic load dynamics during biological invasion: insights from two invasive insect species. bioRxiv, ver.3 peer-reviewed and recommended by PCI Evol Biol https://doi.org/10.1101/2024.09.02.610743

Unraveling genetic load dynamics during biological invasion: insights from two invasive insect speciesEric Lombaert, Aurelie Blin, Barbara Porro, Thomas Guillemaud, Julio S Bernal, Gary Chang, Natalia Kirichenko, Thomas W Sappington, Stefan Toepfer, Emeline Deleury<p>Many invasive species undergo a significant reduction in genetic diversity, i.e. a genetic bottleneck, in the early stages of invasion. However, this reduction does not necessarily prevent them from achieving considerable ecological success and...Bioinformatics & Computational Biology, Population Genetics / GenomicsQuentin Rougemont2024-09-04 10:35:53 View