Biology subjects

Mackintosh, A.

Publications and source records attributed to Mackintosh, A..

13 recordsLinked to original sources

bioRxiv2026

The Nature of Centromeric Repeat Turnovers in the genus Arabidopsis

Centromeres are critical for accurate segregation of chromosomes and are often composed of megabases of tandemly arranged satellite repeats. Yet, despite their conserved function, the DNA sequence of centromeres is, paradoxically, rapidly evolving. To understand the nature of centromeric sequence turnover, we assembled 417 centromeres from nine species representing the entire Arabidopsis genus. In the genus, centromeres are formed by four main satellite repeats with homologous sequences forming central arrays and minor repeat types. We identify the ancestral centromeric repeat type for the Arabidopsis genus and three independent turnovers to different repeats: (1) a complete turnover in A. thaliana, (2) a turnover of seven out of the eight centromeres in the ancestor of A. cebennensis and A. pedemontana, (3) turnovers of three to five centromeres in the genomes of A. halleri and A. lyrata. Most centromeric repeats are also present throughout the genome with shared syntenic locations between Arabidopsis species, and some being similar to parts of transposable elements and genes, suggesting that centromeric repeats originate outside of the centromeres. In allotetraploid A. suecica we find that the repeats from centromeric arrays on one subgenome can transpose and invade the other, likely via transposable element activity. All four main centromeric repeats can recruit the CENH3 (CENP-A) histone variant, however, when a new repeat successfully proliferates in an old array, CENH3 is primarily recruited to the new array marking functional take over. Complete centromeric turnovers occurred in species that experienced severe bottlenecks in their evolutionary history, where new centromeric alleles may have been fixed by genetic drift. Yet, we also observe segregation distortion between two different centromeric repeat types in A. lyrata, suggestive of centromere drive and we propose that both drift and drive contribute to centromeric repeat turnover. Together, our findings reveal the origin of centromeric repeats, mechanisms of repeat proliferation and spread, and the evolutionary dynamics of centromeric repeat turnovers in the Arabidopsis genus.

evolutionary biology↗

bioRxiv2026

The distribution of integer partitions in human genome-wide genealogies reflects gene flow from a super-archaic lineage

Several recent studies have found evidence for ancient gene flow between the ancestors of modern humans and an unsampled super-archaic lineage. Here we present a new, simple approach for characterising this process given genome-wide genealogies sampled from a single population. We summarise genealogies as distributions of integer partitions and show that this captures the temporal signal of tree imbalance left by ancient gene flow. We analyse genealogies from modern humans and find that the integer partition distributions are inconsistent with a history of panmixia but can be explained by gene flow from a super-archaic lineage. Our analysis favours a model of continuous gene flow over pulse-admixture and also recovers a bottleneck in the ancestors of modern humans. This work highlights a clear signal of ancient structure in genealogies of modern humans and provides an inference approach that complements existing methods.

evolutionary biology↗

bioRxiv2025

Estimating the reduction in genetic diversity from background selection under non-equilibrium demography and partial selfing

The effect of natural selection on linked sites has been suggested to be a major determinant of genetic diversity. While it is in principle possible to estimate this effect from genome sequence data, interactions between selection, demography and inbreeding are expected to make inference less reliable. Here we investigate whether the genome-wide reduction in diversity due to background selection ([B]) can be accurately estimated when populations are at demographic non-equilibrium and/or reproduce by partial self-fertilisation. We show that the classic-BGS model is surprisingly robust to both demographic non-equilibrium and low rates of selfing, although both processes do lead to biased estimation of the distribution of fitness effects (DFE) of deleterious mutations. A high rate of selfing leads to poor estimation of both[B] and DFE parameters. We propose an alternative inference approach where background selection, demography and partial selfing are jointly estimated from windowed site frequency spectra. This approach, while approximate in nature, resolves most of the bias observed under the classic-BGS model and can also generate estimates of past demography that account for the effect of background selection and partial selfing. We apply the approach to genome sequence data from Capsella grandiflora and C. orientalis, which have contrasting mating systems and display a forty-fold difference in nucleotide diversity. Our results suggest that background selection has a weak effect on levels of genetic diversity in the outcrosser C. grandiflora ([B] = 0.89) and a more substantial effect in the predominantly selfing species C. orientalis ([B] = 0.44), but that background selection alone cannot explain their disparity in genetic diversity.

evolutionary biology↗

bioRxiv2024

Genealogical asymmetry under the IM model and a two-taxon test for gene flow

Methods for detecting gene flow between populations often rely on asymmetry in the average length of particular genealogical branches, with the ABBA-BABA test being a well known example. Currently, asymmetry-based methods cannot be applied to a pair of populations and such analyses are instead performed using model-based methods. Here we investigate genealogical asymmetry under a two-population isolation-migration model. We focus on genealogies where the first coalescence event is between lineages sampled from different populations, as the external branches of these genealogies have equal expected length as long as there is no post-divergence gene flow. We show that unidirectional gene flow breaks this symmetry and results in the recipient population having longer external branches. We derive expectations for the probability of this genealogical asymmetry under the isolation-migration model and propose a simple statistic (Am) to detect it from genome sequence data. Am provides a two-taxon test for gene flow that only requires a single unphased diploid genome from each population, with no outgroup information. We use analytic expectations and coalescent simulations to explore how recombination, unequal effective population sizes and bidirectional gene flow influence Am and find that the statistic provides unambiguous evidence for gene flow under a continent-island history. We estimate Am for genome sequence data from Heliconius butterflies and Odocoileus deer, generating results consistent with previous model-based analyses. Our work highlights a signal of gene flow overlooked to date and provides a method that complements existing approaches for investigating the demographic history of recently diverged populations.

evolutionary biology↗

bioRxiv2024

Rewinding the ratchet: rare recombination locally rescues neo-W degeneration and generates plateaus of sex-chromosome divergence

Natural selection is less efficient in the absence of recombination. As a result, non-recombining sequences, such as sex chromosomes, tend to degenerate over time. Although the outcomes of recombination arrest are typically observed after many millions of generations, recent neo-sex chromosomes can give insight into the early stages of this process. Here we investigate the evolution of neo-sex chromosomes in the Spanish marbled white butterfly, Melanargia ines, where a Z-autosome fusion has turned the homologous autosome into a non-recombining neo-W chromosome. We show that these neo-sex chromosomes are likely limited to the Iberian population of M. ines, and that they arose around the time when populations in Iberia and North-Africa split, around 1.5 million years ago. Recombination arrest of the neo-W chromosome has led to an excess of premature stop codons and frameshift mutations, while levels of gene expression have remained similar for the neo-W and neo-Z chromosomes, even for genes with loss-of-function mutations. Surprisingly, we identified two regions of[~] 1 Mb at one end of the neo-W that are both less diverged from the neo-Z and less degraded than the rest of the chromosome, suggesting a history of rare but repeated genetic exchange between the two neo-sex chromosomes. These plateaus of neo-sex chromosome divergence suggest that neo-W degradation can be locally reversed by rare recombination between neo-W and neo-Z chromosomes.

evolutionary biology↗

bioRxiv2023

Inferring inter-chromosomal rearrangements and ancestral linkage groups from synteny

Chromosome rearrangements shape the structure of the genome and influence evolutionary processes. Inferring ancestral chromosomes and rearrangements across a phylogenetic tree is therefore an important analysis within evolutionary genetics. One approach to this inference problem is to focus on synteny information, i.e. the co-occurrence of loci on the same chromosome. Although algorithms for inferring ancestral linkage groups (ALGs) and inter-chromosomal rearrangements from synteny have been previously described, they have seldom been applied to modern genome data. Here we implement these algorithms in a command-line tool, syngraph, and evaluate their performance using simulations that include a mix of different rearrangements and types of error. We show that ALGs and rearrangements can be recovered when the rearrangement frequency per-branch is well below the number of chromosomes. We demonstrate that competing models of rearrangement can be inferred by comparing observed results to simulations. Finally, we reanalyse genome assemblies of rhabditid nematodes and find that independent fusions of the same ALGs pose a challenge that is difficult to overcome without gene-order information. Our simulations and analysis of real data demonstrate both the promise and limitations of using synteny information to infer patterns of genome evolution.

evolutionary biology↗

bioRxiv2023

Do chromosome rearrangements fix by genetic drift or natural selection? A test in Brenthis butterflies

Large-scale chromosome rearrangements, such as fissions and fusions, are a common feature of eukaryote evolution. They can have considerable influence on the evolution of populations, yet it remains unclear exactly how rearrangements become established and eventually fix. Rearrangements could fix by genetic drift if they are weakly deleterious or neutral, or they may instead be favoured by positive natural selection. Here we compare genome assemblies of three closely related Brenthis butterfly species and characterise a complex history of fission and fusion rearrangements. An inferred demographic history of these species suggests that rearrangements became fixed in populations with large long-term effective size (Ne). However, we also find large runs of homozygosity within individual genomes and show that a model of population structure with smaller local Ne can reconcile these observations. Using a recently developed analytic framework for characterising hard selective sweeps, we find that chromosome fusions are not enriched for evidence of past sweeps compared to other regions of the genome. Nonetheless, one chromosome fusion in the B. daphne genome is associated with a valley of diversity where genealogical branch lengths are distorted, consistent with a selective sweep. Our results suggest that drift is a stronger force in these populations than suggested by overall genetic diversity, but that the fixation of strongly underdominant rearrangements remains unlikely. Additionally, although chromosome fusions do not typically exhibit signatures of selective sweeps, a single example raises the possibility that natural selection may sometimes play a role in their fixation.

evolutionary biology↗

bioRxiv2023

Chromosome evolution in Lepidoptera

Chromosomes are a central unit of genome organisation. One tenth of all described species on Earth are Lepidoptera, butterflies and moths, and these generally possess 31 holocentric chromosomes. However, a subset of lepidopteran species display dramatic variation in chromosome counts. By analysing 210 chromosomally-complete lepidopteran genomes, the largest analysis of eukaryotic chromosomal-level reference genomes to date, we show that the diverse karyotypes of extant species are derived from 32 ancestral linkage groups, which we term Merian elements. Merian elements have remained largely intact across 250 million years of evolution and diversification. Against this stable background, we identify eight independent lineages that have evaded constraint and undergone extensive reorganisation - either by numerous fissions or a combination of fusion and fission events. Outside these lineages, fusions are rare and fissions are rarer still. Fusions tend to involve small, repeat-rich Merian elements and/or the Z chromosome. Together, our results reveal the constraints on genome architecture in Lepidoptera and enable a deeper understanding of the importance of chromosomal rearrangements in shaping the evolution of eukaryotic genomes.

evolutionary biology↗

bioRxiv2022

Chromosome fissions and fusions act as barriers to gene flow between Brenthis fritillary butterflies

Chromosome rearrangements are thought to promote reproductive isolation between incipient species. However, it is unclear how often, and under what conditions, fission and fusion rearrangements act as barriers to gene flow. Here we investigate speciation between two largely sympatric fritillary butterflies, Brenthis daphne and B. ino. We use a composite likelihood approach to infer the demographic history of these species from whole genome sequence data. We then compare chromosome-level genome assemblies of individuals from each species and identify a total of nine chromosome fissions and fusions. Finally, we fit a demographic model where effective population sizes and effective migration rate vary across the genome, allowing us to quantify the effects of chromosome rearrangements on reproductive isolation. We show that chromosomes involved in rearrangements experienced less effective migration since the onset of species divergence and that genomic regions near rearrangement points have a further reduction in effective migration rate. Our results suggest that the evolution of multiple rearrangements in the B. daphne and B. ino populations, including alternative fusions of the same chromosomes, have resulted in a reduction in gene flow. While fission and fusion of chromosomes are unlikely to be the only processes that have led to speciation between these butterflies, this study shows that these rearrangements can directly promote reproductive isolation and may be involved in speciation when karyotypes evolve quickly.

evolutionary biology↗

bioRxiv2022

The genome sequence of the scarce swallowtail, Iphiclides podalirius

The scarce swallowtail, Iphiclides podalirius (Linnaeus, 1758), is a species of butterfly in the family Papilionidae. Here we present a chromosome-level genome assembly for I. podalirius as well as gene and transposable element annotations. We estimate heterozygosity within different partitions of the genome and find a negative correlation between chromosome length and heterozygosity at fourfold-degenerate sites. This high quality genome assembly, the first for any species in the tribe Leptocircini, will be a valuable resource for population genomics in the genus Iphiclides and comparative genomics more generally.

evolutionary biology↗

bioRxiv2021

The genome sequence of the lesser marbled fritillary, Brenthis ino, and evidence for a segregating neo-Z chromosome

The lesser marbled fritillary, Brenthis ino (Rottemburg, 1775), is a species of Palearctic butterfly. Male B. ino individuals have been reported to have between 12 and 14 pairs of chromosomes, a much reduced chromosome number than is typical in butterflies. Here we present a chromosome-level genome assembly for B. ino, as well as gene and transposable element annotations. The assembly is 411.8 Mb in span with contig and scaffold N50s of 9.6 and 29.5 Mb respectively. We also show evidence that the male individual from which we generated HiC data was heterozygous for a neo-Z chromosome, consistent with inheriting 14 chromosomes from one parent and 13 from the other. This genome assembly will be a valuable resource for studying chromosome evolution in Lepidoptera, as well as for comparative and population genomics more generally.

evolutionary biology↗

bioRxiv2021

Inversions maintain differences between migratory phenotypes of a songbird

Long-distance migration requires adaptations in a suite of behavioral, physiological and morphological traits. However, almost nothing is known about the genetic basis of these adaptations. The willow warbler Phylloscopus trochilus occurs in Europe with a northern and southern subspecies that show drastically different migration routes and wintering areas. Previous studies have demonstrated that the subspecies are genetically extremely similar except for three divergent chromosome regions, of which two are associated with the differences in migratory phenotypes and one is associated with an environmental gradient. Here we use a combination of long-read sequencing, linked-read sequencing and optical mapping to construct more complete and contiguous assemblies for both of the subspecies. We find evidence for inversions in each of the three divergent regions, which range from 0.4 to 13 Mb in size, and that breakpoints are associated with tandem repeat arrays or segmental duplications. The divergence times between inverted and non-inverted haplotypes are similar across the regions ([~]1.2 Myrs), which is compatible with a scenario where the inversions arose in either of two allopatric populations that subsequently hybridized. The improved genome assemblies and annotation also allowed us to detect additional functional differences in the divergent regions that provide candidate genes for migration and local adaptations to environmental gradients.

evolutionary biology↗

bioRxiv2019

The determinants of genetic diversity in butterflies - Lewontin's paradox revisited

Under the neutral theory genetic diversity is expected to be a simple function of population size. However, comparative studies have consistently failed to find any strong correlation between measures of census population size and genetic diversity. Instead, a recent comparative study across several animal phyla identified propagule size as the strongest predictor of genetic diversity, suggesting that r-strategists that produce many offspring but invest little in each, have greater long-term effective population sizes. We present a comparison of genome-wide levels of genetic diversity across 38 species of European butterflies (Papilionoidea). We show that across butterflies, genetic diversity varies over an order of magnitude and that this variation cannot be explained by differences in abundance, fecundity, host plant use or geographic range. Instead, we find that genetic diversity is negatively correlated with body size and positively with the length of the genetic map. This suggests that variation in genetic diversity is determined both by fluctuation in Ne and the effect of selection on linked neutral sites.

evolutionary biology↗