Biology subjects

Amos, W.

Publications and source records attributed to Amos, W..

11 recordsLinked to original sources

bioRxiv2025

Unexpected D-tour Ahead: Why the D-Statistic, applied to Humans, Measures Mutation Rate Variation not Neanderthal Introgression

The D statistic is widely used to infer introgression and played a pivotal role in establishing as fact that humans interbred with Neanderthals, leaving a lasting genetic legacy. However, D relies on two untested assumptions: mutation rate constancy between groups and a negligible contribution from recurrent mutations. Together, these preclude a previously ignored alternative explanation of the data based on mutation-rate variation across human populations. Here we show that neither assumption is valid and infer that essentially all sites contributing to non-zero D carry recurrent mutations. When D is calculated separately for different sequence motifs, it varies far more than can be explained using a model based on introgressed haplotypes, where non-independence due to being located on the same haplotype largely prevents different motifs from generating different values of D. Large variation in D between triplets appears only possible if D is driven by processes acting at the level of individual bases. We further show that D is dominated by sites where the Neanderthal allele matches the human major allele and, more specifically, where the Neanderthal allele is fixed in humans outside Africa. This is the exact opposite of expectations under the introgression hypothesis, where Neanderthal alleles should mostly be rare and found only outside Africa. Finally, we tested a new model in which heterozygosity modulates mutation rate. Remarkably, heterozygosity differences, relative mutation rate, and D are all strongly inter-correlated, not only in African - non-African comparisons but also in comparisons among African and among non-African population pairs, and even across the genome. We conclude that the mutation rate variation hypothesis provides a more compelling explanation for the observed patterns in human-Neanderthal genetic relationships than the introgression hypothesis and that the concept of archaic introgression into humans and its implications for hominin-derived traits must be rethought.

evolutionary biology↗

bioRxiv2022

Eusocial evolution without a nest: kin structure of social aphids forming open colonies on bamboo

Living in nests is an almost universal feature of eusocial animals. In some aphids, however, sterile soldier castes have evolved in open colonies without a nest. To clarify the factors promoting the evolution of eusociality in these colonies, we used newly developed microsatellite markers to compare the kin structure of the open colonies of two aphid species on bamboo: the non-eusocial colonies of Astegopteryx bambucifoliae and the eusocial colonies of Pseudoregma alexanderi on Dendrocalamus latiflorus. Our samples, from over 1,000 hectares, contained 99 clones of A. bambucifoliae and 19 of P. alexanderi. Clonal mixing occurred in both species: average pairwise relatedness within a colony was 0.54 in A. bambucifoliae and 0.71 in P. alexanderi. Each clone of A. bambucifoliae occurred in a unique location, whereas those of P. alexanderi occurred in multiple locations and more than 90% of individuals came from just four clones. There was significant genetic variation among different colonies in the same clump (stem-cluster) in A. bambucifoliae but not in P. alexanderi, indicating that P. alexanderi colonies in a single clump are genetically homogenized, functioning as a large colony. In P. alexanderi, the proportion of sterile soldiers to normal first-instar nymphs was significantly different across the four clones. Our results indicate that the lack of input of migrants from the primary host and feeding on a large, stable host plant are important ecological factors that might favour the evolution of eusociality, enabling the production of genetically homogenised, large, and long-lived colonies. After eusociality evolves on the secondary host, the optimal strategy of soldier production might vary between different clones. Significance StatementNest-living has often been considered to be a necessary condition for the evolution of eusociality. In a small number of aphid species, however, sterile soldier castes have evolved in open colonies without a nest. To understand why these aphids are unique, we examined the kin structure and genetic relatedness of individuals within eusocial and non-eusocial open colonies of two aphid species on bamboo. We found that clonal mixing occurred in both species, but the eusocial colonies are more genetically homogenized, functioning as a large colony. Our results suggest that ecological conditions that promote genetically homogenized, large and long-lived colonies are important for the evolution of eusociality in these aphids. We propose that the open colonies of social aphids provide an ideal model system in which to study the evolution of altruism.

evolutionary biology↗

bioRxiv2021

Decomposing the admixture statistic, D, suggests a negligible contribution due to archaic introgression into humans.

It is widely accepted that non-African humans carry a few percent of Neanderthal DNA due to historical inter-breeding. However, methods used to infer a legacy all assume that mutation rate is constant and that back-mutations can be ignored. Here I decompose the widely used admixture statistic, D, in a way that allows the overall signal to be apportioned to different classes of contributing site. I explore three main characteristics: whether the putative Neanderthal allele is likely derived or ancestral; whether an allele is fixed in one of the two human populations; and the type of mutation that created the polymorphism, defined by the base that mutated and immediately flanking bases. The entire signal used to infer introgression can be attributed to a subset of sites where the putative Neanderthal base is common in Africans and fixed in non-Africans. Moreover, the four triplets containing highly mutable CpG motifs alone contribute 29%. In contrast, sites expected to dominate the signal if introgression has occurred, where the putative Neanderthal allele is absent from Africa and rare outside Africa, contribute negligibly. Together, these observations show that D does not capture a signal due to introgression but instead they support an alternative model in which a higher mutation rate in Africa drives increased divergence from the ancestral state.

evolutionary biology↗

bioRxiv2020

A test of the hypothesis that variable mutation rates create signals that have previously been interpreted as evidence of archaic introgression into humans.

It is widely accepted that non-African humans carry 1-2% Neanderthal DNA due to historical inter-breeding. However, inferences about introgression rely on a critical assumption that mutation rate is constant and that back-mutations are too rare to be important. Both these assumptions have been challenged, and recent evidence points towards an alternative model where signals interpreted as introgression are driven mainly by higher mutation rates in Africa. In this model, non-Africans appear closer to archaics not because they harbour introgressed fragments but because Africans have diverged more. Here I test this idea by using the density of rare, human-specific variants (RHSVs) as a proxy for recent mutation rate. I find that sites that contribute most to the signal interpreted as introgression tend to occur in tightly defined regions spanning only a few hundred bases in which mutation rate differs greatly between the two human populations being compared. Mutation rate is invariably higher in the population into which introgression is not inferred. I confirmed that RHSV density reflects mutation rate by conducting a parallel analysis looking at the density of RHSVs around sites with three alleles, an independent class of site that also requires recurrent mutations to form. Near-identical peaks in RHSV density are found, suggesting a common cause. Similarly, coalescent simulations confirm that, with constant mutation rate, introgressed fragments do not occur preferentially in regions with a high density of rare, human-specific variants. Together, these observations are difficult to reconcile with a model where excess base-sharing is driven by archaic legacies but instead provide support for a higher mutation rate inside Africa driving increased divergence from the ancestral human state.

evolutionary biology↗

bioRxiv2020

Allelic diversity of the PRDM9 coding minisatellite in minke whales

We explored the structure and variability of the Prdm9 gene, which codes for the PRDM9 protein, in samples of the minke whales from the Atlantic, Pacific and Southern Oceans. The PRDM9 protein controls the reshuffling of parental genomes in most metazoans and we show that minke whale possess all the features characteristic of PRDM9-directed recombination initiation, including complete KRAB, SSXRD and SET domains and a rapidly evolving array of C2H2-type-Zincfingers (ZnF). We uncovered eighteen novel PRDM9 variants and evidence of rapid evolution, particularly at DNA-recognizing positions that evolve under positive selection. At different geographical scales, we observed extensive Prdm9 allelic diversity in Antarctic minke whales (Balaenoptera bonarensis) that, conversely, lack observable population differentiation in mitochondrial DNA and microsatellites. In contrast, a single PRDM9 variant is shared between all Common Minke whales and even across subspecies boundaries of North Atlantic (B. a. acutorostrata) and North Pacific (B. a. scammoni) minke whale, which do show clear population differentiation. PRDM9 variation of whales predicts distinct recombination initiation landscapes genome-wide, which has possible consequences for speciation.

genetics↗

bioRxiv2020

Statistics used to infer inter-breeding between humans and Neanderthals are strongly predicted by flanking sequence heterozygosity.

A large and rapidly expanding literature has grown out of the observation that humans carry a genetic legacy reflecting ancient inter-breeding with archaic hominins such as Neanderthals and Denisovans. However, a recent study suggests that a commonly used statistic used to assess legacy size, D, is driven mainly by heterozygous sites in Africa acting to increase divergence from our common ancestor rather than introgressed fragments outside Africa reducing divergence. To test this new model, I analysed how D is influenced by heterozygosity within a kilobase of each putative introgressed base. I find that flanking heterozygosity is a potent predictor of D, with introgression always being inferred as having occurred into the population with lower heterozygosity. This pattern cannot be driven by any introgressed fragments themselves, which simulations show create the exact converse pattern, but instead appears to be generated by heterozygosity acting to drive increased divergence from the ancestral sequence. This new model explains why introgression of haploid or semi-haploid regions is essentially lacking and why introgression is often inferred around immune genes and other regions under strong selection. More generally, these results raise the possibility that reported legacies are largely an artefact arising out of the false assumption that mutation rate is constant.

evolutionary biology↗

bioRxiv2020

Genetic signatures of human brain structure: A comparison between GWAS and relatedness-based regression

Identifying the genetic variations impacting human brain structure and their further effects on cognitive functions, is important for our understanding of the fundamental bases of cognition. In this study, we take two different approaches to this issue: classical genome-wide association analysis (GWAS) and a relatedness-based regression approach (REL) to search for associations between genotype and brain structural measures of gray matter and white matter. Instead of searching genetic variants by testing the association between a phenotype trait and the genotype of each single-nucleotide polymorphism (SNP) as in GWAS, REL takes advantage of multiple SNPs within a genomic window as a single measure, which potentially find associations wherever the functional SNP is in linkage disequilibrium (LD) with SNPs that have been sampled. We also conducted a simulation analysis to systemically compare GWAS and REL with respect to different levels of LD. Both methods succeed in identifying genetic variations associated with regional and global brain structural measures and tend to give complementary results due to the different aspects of genetic properties used. Simulation results suggest that GWAS outperforms REL when the signal is relatively weak. However, the collective effects due to local LD boost the performance of REL with increasing signal strength, resulting in better performance than GWAS. Our study suggests that the optimal approach may vary across the genome and that pre-testing for LD could allow GWAS to be preferred where LD is high and REL to be used where LD is low, or the local pattern of LD is complex.

genetics↗

bioRxiv2020

Signatures of introgression across the allele frequency spectrum

The detection of introgression from genomic data is transforming our view of species and the origins of adaptive variation. Among the most widely used approaches to detect introgression is the so-called ABBA BABA test or D statistic, which identifies excess allele sharing between non-sister taxa. Part of the appeal of D is its simplicity, but this also limits its informativeness, particularly about the timing and direction of introgression. Here we present a simple extension, D frequency spectrum or DFS, in which D is partitioned according to the frequencies of derived alleles. We use simulations over a large parameter space to show how DFS caries information about various factors. In particular, recent introgression reliably leads to a peak in DFS among low-frequency derived alleles, whereas violation of model assumptions can lead to a lack of signal at low-frequencies. We also reanalyse published empirical data from six different animal and plant taxa, and interpret the results in the light of our simulations, showing how DFS provides novel insights. We currently see DFS as a descriptive tool that will augment both simple and sophisticated tests for introgression, but in the future it may be usefully incorporated into probabilistic inference frameworks.

evolutionary biology↗

bioRxiv2019

mtDNA-based reconstructions of change in effective population sizes of Holarctic birds do not agree with their reconstructed range sizes based on paleoclimates

During the Quaternary, large climate oscillations had profound impacts on the distribution, demography and diversity of species globally. Birds offer a special opportunity for studying these impacts because surveys of geographical distributions, publicly-available genetic sequence data, and the existence of species with adaptations to life in structurally different habitats, permit large-scale comparative analyses. We use Bayesian Skyline Plot (BSP) analysis of mitochondrial DNA to reconstruct profiles depicting how effective population size (Ne) may have changed over time, focussing on variation in the effect of the last deglaciation among 102 Holarctic species. Only 3 species showed a decline in Ne since the Last Glacial Maximum (LGM) and 7 showed no sizeable change, whilst 92 profiles revealed an increase in Ne. Using bioclimatic Species Distribution Models (SDMs), we also estimated changes in species potential range extent since the LGM. Whilst most modelled ranges also increased, we found no correlation across species between the magnitude of change in range size and change in Ne. The lack of correlation between SDM and BSP reconstructions could not be reconciled even when range shifts were considered. We suggest the lack of agreement between these measures might be linked to changes in population densities which can be independent of range changes. We caution that interpreting either SDM or BSPs independently is problematic and potentially misleading. Additionally, we found that Ne of wetland species tended to increase later than species from terrestrial habitats, possibly reflecting a delayed increase in the extent of this habitat type after the LGM.

evolutionary biology↗

bioRxiv2019

Differential base-sharing between humans and Neanderthals: inter-breeding or greater mutability in heterozygotes?

The idea that humans interbred with other Hominins, most notably Neanderthals, is now accepted as fact. The finding of hybrid skeletons shows that fertile matings did occur. However, inferences about the size of the resulting legacy assume that back-mutations are rare enough to be ignored and that mutation rate does not vary. In reality, back-mutations are common, mutation rate does vary between populations and there is mounting evidence that heterozygosity and mutation rate covary. If so, the large loss of heterozygosity that occurred when humans migrated out of Africa would have reduced the mutation rate, leaving Africans to diverge faster from our common ancestor and from related lineages like Neanderthals. To test whether this idea impacts estimates of introgressed fraction, I calculated D, a measure of relative base-sharing with Neanderthals, and heterozygosity difference between all pairwise combinations of populations in the 1000 genomes Phase 3 data. D and heterozygosity difference are ubiquitously negatively correlated across all comparisons, between all regions and even between populations within each major region including Africa. In addition, the larger sample of populations in the Simons Genome Diversity project reveals a pan-Eurasian correlation between Neanderthal and Denisovan fraction. These correlations challenge a simple hybridisation model but do seem consistent with a model where more heterozygous human populations tend to diverge faster from Neanderthals than populations with lower heterozygosity. Indeed, the strongest correlation between Neanderthal content and geography indicates and origin where humans likely left Africa, exactly mimicking the pattern seen for loss of heterozygosity. Such a model explains why evidence for inter-breeding is found more or less wherever archaic and human populations are compared. How much of variation in D is due to introgression and how much is due to heterozygosity-mediated variation in mutation rate remains to be determined.\n\nAuthor summaryThe idea that humans inter-bred with related lineages such as Neanderthals, leaving an appreciable legacy in modern genomes, has rapidly progressed from shocking revelation to accepted dogma. My analysis explores an alternative model in which mutation rate slowed when diversity was lost in a population bottleneck as humans moved out of Africa to colonise the world. I find that, across Eurasia, the size of inferred legacy closely matches the pattern of diversity loss but shows no relationship to where human and Neanderthal populations likely overlapped. My results do not challenge the idea that some inter-breeding occurred, but they do indicate that some, much or even most of the signal that has be attributed entirely to archaic legacies, arises from unexpected variation in mutation rate. More generally, my analysis helps explain why inter-breeding is inferred almost wherever tests are conducted even though most species avoid hybridisation.

evolutionary biology↗

bioRxiv2017

Testing an alternative explanation for relatively greater base-sharing between Neanderthals and non-African humans

Most accept that non-African humans share [~]2% of their genome with Neanderthals (1) and that inter-breeding occurred between several archaic lineages (2-4). However, most evidence assumes that mutation rate is constant. It has been suggested that heterozygosity is mutagenic (5-8). If so, an alternative explanation of the data becomes possible. Instead of non-Africans sharing relatively more bases with Neanderthals due to interbreeding, Africans could appear unexpectedly divergent due to their mutation rate not having been lowered when diversity was lost during the out of Africa bottleneck. I therefore tested a series of predictions aimed at distinguishing mutation slowdown from inter-breeding. Predictions from mutation slowdown are generally better supported. For example, the signal used to infer inter-breeding remains even when Neanderthal sequences are excluded. I conclude that, while some inter-breeding probably did occur, an appreciable component of the signal seems better explained by mutation slowdown.

genomics↗