ABSTRACT
African antelope diversity is a globally unique vestige of a much richer world-wide Pleistocene megafauna. Despite this, the evolutionary processes leading to the prolific radiation of African antelopes are not well understood. Here, we sequenced 145 whole genomes from both subspecies of the waterbuck (Kobus ellipsiprymnus), an African antelope believed to be in the process of speciation. We investigated genetic structure and population divergence and found evidence of a mid-Pleistocene separation on either side of the eastern Great Rift Valley, consistent with vicariance caused by a rain shadow along the so-called 'Kingdon's Line'. However, we also found pervasive evidence of both recent and widespread historical gene flow across the Rift Valley barrier. By inferring the genome-wide landscape of variation among subspecies, we found 14 genomic regions of elevated differentiation, including a locus that may be related to each subspecies' distinctive coat pigmentation pattern. We investigated these regions as candidate speciation islands. However, we observed no significant reduction in gene flow in these regions, nor any indications of selection against hybrids. Altogether, these results suggest a pattern whereby climatically driven vicariance is the most important process driving the African antelope radiation, and suggest that reproductive isolation may not set in until very late in the divergence process. This has a significant impact on taxonomic inference, as many taxa will be in a gray area of ambiguous systematic status, possibly explaining why it has been hard to achieve consensus regarding the species status of many African antelopes. Our analyses demonstrate how population genetics based on low-depth whole genome sequencing can provide new insights that can help resolve how far lineages have gone along the path to speciation.
ABSTRACT
The microbial communities of the oral cavity are important elements of oral and systemic health. With emerging evidence highlighting the heritability of oral bacterial microbiota, this study aimed to identify host genome variants that influence oral microbial traits. Using data from 16S rRNA gene amplicon sequencing, we performed genome-wide association studies with univariate and multivariate traits of the salivary microbiota from 610 unrelated adults from the Danish ADDITION-PRO cohort. We identified six single nucleotide polymorphisms (SNPs) in human genomes that showed associations with abundance of bacterial taxa at different taxonomical tiers (P < 5 × 10-8). Notably, SNP rs17793860 surpassed our study-wide significance threshold (P < 1.19 × 10-9). Additionally, rs4530093 was linked to bacterial beta diversity (P < 5 × 10-8). Out of these seven SNPs identified, six exerted effects on metabolic traits, including glycated hemoglobin A1c, triglyceride and high-density lipoprotein cholesterol levels, the risk of type 2 diabetes and stroke. Our findings highlight the impact of specific host SNPs on the composition and diversity of the oral bacterial community. Importantly, our results indicate an intricate interplay between host genetics, the oral microbiota, and metabolic health. We emphasize the need for integrative approaches considering genetic, microbial, and metabolic factors.
Subject(s)
Genome-Wide Association Study , Microbiota , Mouth , Polymorphism, Single Nucleotide , Humans , Female , Microbiota/genetics , Male , Middle Aged , Mouth/microbiology , Adult , RNA, Ribosomal, 16S/genetics , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/microbiology , Saliva/microbiology , AgedABSTRACT
The blue wildebeest (Connochaetes taurinus) is a keystone species in savanna ecosystems from southern to eastern Africa, and is well known for its spectacular migrations and locally extreme abundance. In contrast, the black wildebeest (C. gnou) is endemic to southern Africa, barely escaped extinction in the 1900s and is feared to be in danger of genetic swamping from the blue wildebeest. Despite the ecological importance of the wildebeest, there is a lack of understanding of how its unique migratory ecology has affected its gene flow, genetic structure and phylogeography. Here, we analyze whole genomes from 121 blue and 22 black wildebeest across the genus' range. We find discrete genetic structure consistent with the morphologically defined subspecies. Unexpectedly, our analyses reveal no signs of recent interspecific admixture, but rather a late Pleistocene introgression of black wildebeest into the southern blue wildebeest populations. Finally, we find that migratory blue wildebeest populations exhibit a combination of long-range panmixia, higher genetic diversity and lower inbreeding levels compared to neighboring populations whose migration has recently been disrupted. These findings provide crucial insights into the evolutionary history of the wildebeest, and tangible genetic evidence for the negative effects of anthropogenic activities on highly migratory ungulates.
Subject(s)
Antelopes , Animals , Antelopes/genetics , Ecosystem , Africa, Eastern , Africa, Southern , Anthropogenic EffectsABSTRACT
CONTEXT: Insulin sensitivity (IS) is an important factor in type 2 diabetes (T2D) and can be estimated by many different indices. OBJECTIVE: We aimed to compare the genetic components underlying IS indices obtained from fasting and oral glucose-stimulated plasma glucose and serum insulin levels. METHODS: We computed 21 IS indices, classified as fasting, OGTT0,120 and OGTT0,30,120 indices, using fasting and oral glucose tolerance test (OGTT) data in two cohorts. We used data from a family cohort (n=313) to estimate the heritability and the genetic and phenotypic correlations of IS indices. The population cohort, Inter99 (n=5,343), was used to test for associations between IS indices and 426 genetic variants known to be associated with T2D. RESULTS: Heritability estimates of IS indices ranged between 19% and 38%. Fasting and OGTT0,30,120 indices had high genetic (ρG) and phenotypic (ρP) pairwise correlations (ρG and ρP: 0.88 to 1) The OGTT0,120 indices displayed a wide range of pairwise correlations (ρG: 0.17-1.00 and ρP: 0.13-0.97). We identified statistically significant associations between IS indices and established T2D-associated variants. The PPARG rs11709077 was associated only with fasting indices, and PIK3R rs4976033 only with OGTT0,30,120 indices. The variants in FAM63A/MINDY1, GCK, C2CD4A/B, and FTO loci were associated only with OGTT0,120 indices. CONCLUSION: Even though the IS indices mostly share a common genetic background, notable differences emerged between OGTT0,120 indices. The fasting and OGTT based indices have distinct associations with T2D risk variants. This work provides a basis for future large-scale genetic investigations into the differences between IS indices.
ABSTRACT
Strong genetic structure has prompted discussion regarding giraffe taxonomy,1,2,3 including a suggestion to split the giraffe into four species: Northern (Giraffa c. camelopardalis), Reticulated (G. c. reticulata), Masai (G. c. tippelskirchi), and Southern giraffes (G. c. giraffa).4,5,6 However, their evolutionary history is not yet fully resolved, as previous studies used a simple bifurcating model and did not explore the presence or extent of gene flow between lineages. We therefore inferred a model that incorporates various evolutionary processes to assess the drivers of contemporary giraffe diversity. We analyzed whole-genome sequencing data from 90 wild giraffes from 29 localities across their current distribution. The most basal divergence was dated to 280 kya. Genetic differentiation, FST, among major lineages ranged between 0.28 and 0.62, and we found significant levels of ancient gene flow between them. In particular, several analyses suggested that the Reticulated lineage evolved through admixture, with almost equal contribution from the Northern lineage and an ancestral lineage related to Masai and Southern giraffes. These new results highlight a scenario of strong differentiation despite gene flow, providing further context for the interpretation of giraffe diversity and the process of speciation in general. They also illustrate that conservation measures need to target various lineages and sublineages and that separate management strategies are needed to conserve giraffe diversity effectively. Given local extinctions and recent dramatic declines in many giraffe populations, this improved understanding of giraffe evolutionary history is relevant for conservation interventions, including reintroductions and reinforcements of existing populations.
Subject(s)
Giraffes , Animals , Giraffes/genetics , Ruminants/genetics , Biological Evolution , Phylogeny , Genetic DriftABSTRACT
Several African mammals exhibit a phylogeographic pattern where closely related taxa are split between West/Central and East/Southern Africa, but their evolutionary relationships and histories remain controversial. Bushpigs (Potamochoerus larvatus) and red river hogs (P. porcus) are recognised as separate species due to morphological distinctions, a perceived lack of interbreeding at contact, and putatively old divergence times, but historically, they were considered conspecific. Moreover, the presence of Malagasy bushpigs as the sole large terrestrial mammal shared with the African mainland raises intriguing questions about its origin and arrival in Madagascar. Analyses of 67 whole genomes revealed a genetic continuum between the two species, with putative signatures of historical gene flow, variable FST values, and a recent divergence time (<500,000 years). Thus, our study challenges key arguments for splitting Potamochoerus into two species and suggests their speciation might be incomplete. Our findings also indicate that Malagasy bushpigs diverged from southern African populations and underwent a limited bottleneck 1000-5000 years ago, concurrent with human arrival in Madagascar. These results shed light on the evolutionary history of an iconic and widespread African mammal and provide insight into the longstanding biogeographic puzzle surrounding the bushpig's presence in Madagascar.
Subject(s)
Mammals , Humans , Animals , Swine , Madagascar , Phylogeny , Porosity , Phylogeography , Mammals/geneticsABSTRACT
Mucopolysaccharidoses (MPSs) are inherited lysosomal storage disorders (LSDs). MPSs are caused by excessive accumulation of mucopolysaccharides due to missing or deficiency of enzymes required for the degradation of specific macromolecules. MPS I-IV, MPS VI, MPS VII, and MPS IX are sub-types of mucopolysaccharidoses. Among these, MPS III (also known as Sanfilippo) and MPS IV (Morquio) syndromes are lethal and prevalent sub-types. This study aimed to identify causal genetic variants in cases of MPS III and MPS IV and characterize genotype-phenotype relations in Pakistan. We performed clinical, biochemical and genetic analysis using Whole Genome Sequencing (WGS) in 14 Pakistani families affected with MPS III or MPS IV. Patients were classified into MPS III by history of aggressive behaviors, dementia, clear cornea and into MPS IV by short trunk, short stature, reversed ratio of upper segment to lower segment with a short upper segment. Data analysis and variant selections were made based on segregation analysis, examination of known MPS III and MPS IV genes, gene function, gene expression, the pathogenicity of variants based on ACMG guidelines and in silico analysis. In total, 58 individuals from 14 families were included in the present study. Six families were clinically diagnosed with MPS III and eight families with MPS IV. WGS revealed variants in MPS-associated genes including NAGLU, SGSH, GALNS, GNPTG as well as the genes VWA3B, BTD, and GNPTG which have not previously associated with MPS. One family had causal variants in both GALNS and BTD. Accurate and early diagnosis of MPS in children represents a helpful step for designing therapeutic strategies to protect different organs from permanent damage. In addition, pre-natal screening and identification of genetic etiology will facilitate genetic counselling of the affected families. Identification of novel causal MPS genes might help identifying new targeted therapies to treat LSDs.
ABSTRACT
Background: Lysosomal storage disorders (LSDs) are a group of inherited metabolic diseases, which encompass more than 50 different subtypes of pathologies. These disorders are caused by defects in lysosomal enzymes, transporters, and other non-lysosomal proteins. Mucopolysaccharidosis (MPS) is the most common subgroup of lysosomal storage disorders in which the body is unable to properly breakdown mucopolysaccharides. The aim of the present study was to identify novel genes and pathogenic variants in families from diverse regions of Pakistan with clinically diagnosed mucopolysaccharidosis type I and mucopolysaccharidosis type II. Methods: Clinical diagnosis identified 12 with mucopolysaccharidosis I and 2 with mucopolysaccharidosis II in 14 families and whole genome sequencing (WGS) was performed to identify the causative variations in 15 affected individuals. Twenty-two unaffected individuals including parents or normal siblings of patients were also sequenced. Putative causal variants were identified by co-segregation and functional annotation. Results: Analysis of whole genome sequencing data revealed ten novel and six previously reported variants in lysosomal storage disorders-associated genes (IDUA, GALNS, SGSH, GAA, IDS, ALDOB, TRAPPC4, MASP1, SMARCAL, KIAA1109, HERC1, RRAS2) and a novel candidate gene (ABCA5) for lysosomal storage disorder-like phenotypes, which has previously been associated with symptoms strongly related with lysosomal storage disorder in animal models. Conclusion: Multigenic inheritance was found in several families highlighting the importance of searching for homozygous pathogenic variants in several genes also in families with a high degree of consanguinity.
ABSTRACT
In recombinant protein expression using Chinese hamster ovary (CHO) cells, chemically defined media contain essential amino acids such as branched chain amino acids (BCAAs) leucine, isoleucine and valine. Availability of amino acids is critical as these are building blocks for protein synthesis. However, breakdown of amino acids can lead to build up of toxic intermediates and metabolites that decrease cell growth, productivity and product quality. BCAA catabolism also hampers the usage of BCAAs for protein synthesis. In this work we studied the effects of disrupting the genes responsible for the first step of BCAA catabolism: branched chain aminotransferase 1 (Bcat1) and branched chain aminotransferase 2 (Bcat2). We evaluated the effect of disrupting the genes individually and in combination, and examined the effects in producer and non-producer host cells. Our experiments show that Bcat1 disruption improves cell growth in producer cells, but not in non-producers. Conversely, Bcat2 has a minor negative effect on growth in producer cells, and none in non-producers. Combined Bcat1 and Bcat2 disruption improves growth in producer cells. By-product metabolism is cell line-, clone- and producer-dependent. Overall, our results show that the effects of targeting Bcat1 and/or Bcat2 are cell line-dependent, and seemingly linked to the burden of recombinant protein expression.
Subject(s)
Amino Acids, Branched-Chain/metabolism , Transaminases/metabolism , Animals , CHO Cells , Cell Proliferation , Cell Survival , Cricetulus , Culture Media/metabolism , Mutation , Protein Biosynthesis , Transaminases/geneticsABSTRACT
Contamination from both present-day humans and postmortem microbial sources is a common challenge in ancient DNA studies. Here we present a suite of tools to assist in the assessment of contamination in ancient DNA data sets. These tools perform standard tests of authenticity of ancient DNA data including detecting the presence of postmortem damage signatures in sequence alignments and quantifying the amount of present-day human contamination.
Subject(s)
Cell Nucleus/genetics , DNA Contamination , DNA, Ancient/analysis , DNA, Mitochondrial/genetics , Sequence Analysis, DNA/methods , Genome, Mitochondrial , HumansABSTRACT
Dynamic evolutionary processes and complex structure make the Y chromosome among the most diverse and least understood regions in mammalian genomes. Here, we present an annotated assembly of the male specific region of the horse Y chromosome (eMSY), representing the first comprehensive Y assembly in odd-toed ungulates. The eMSY comprises single-copy, equine specific multi-copy, PAR transposed, and novel ampliconic sequence classes. The eMSY gene density approaches that of autosomes with the highest number of retained X-Y gametologs recorded in eutherians, in addition to novel Y-born and transposed genes. Horse, donkey and mule testis RNAseq reveals several candidate genes for stallion fertility. A novel testis-expressed XY ampliconic sequence class, ETSTY7, is shared with the parasite Parascaris genome, providing evidence for eukaryotic horizontal transfer and inter-chromosomal mobility. Our study highlights the dynamic nature of the Y and provides a reference sequence for improved understanding of equine male development and fertility.
Subject(s)
Evolution, Molecular , Fertility/genetics , Horses/genetics , Y Chromosome/genetics , Animals , Ascaridoidea/genetics , Equidae/genetics , Gene Dosage/genetics , Gene Transfer, Horizontal , Hybridization, Genetic , Male , Phylogeny , Testis/metabolism , X Chromosome/geneticsABSTRACT
The Eneolithic Botai culture of the Central Asian steppes provides the earliest archaeological evidence for horse husbandry, ~5500 years ago, but the exact nature of early horse domestication remains controversial. We generated 42 ancient-horse genomes, including 20 from Botai. Compared to 46 published ancient- and modern-horse genomes, our data indicate that Przewalski's horses are the feral descendants of horses herded at Botai and not truly wild horses. All domestic horses dated from ~4000 years ago to present only show ~2.7% of Botai-related ancestry. This indicates that a massive genomic turnover underpins the expansion of the horse stock that gave rise to modern domesticates, which coincides with large-scale human population expansions during the Early Bronze Age.
Subject(s)
Horses/classification , Horses/genetics , Animals , DNA, Ancient , Genome , Horses/anatomy & histology , Phenotype , PhylogenyABSTRACT
Reconstructing the colonization and demographic dynamics that gave rise to extant forests is essential to forecasts of forest responses to environmental changes. Classical approaches to map how population of trees changed through space and time largely rely on pollen distribution patterns, with only a limited number of studies exploiting DNA molecules preserved in wooden tree archaeological and subfossil remains. Here, we advance such analyses by applying high-throughput (HTS) DNA sequencing to wood archaeological and subfossil material for the first time, using a comprehensive sample of 167 European white oak waterlogged remains spanning a large temporal (from 550 to 9,800 years) and geographical range across Europe. The successful characterization of the endogenous DNA and exogenous microbial DNA of 140 (~83%) samples helped the identification of environmental conditions favouring long-term DNA preservation in wood remains, and started to unveil the first trends in the DNA decay process in wood material. Additionally, the maternally inherited chloroplast haplotypes of 21 samples from three periods of forest human-induced use (Neolithic, Bronze Age and Middle Ages) were found to be consistent with those of modern populations growing in the same geographic areas. Our work paves the way for further studies aiming at using ancient DNA preserved in wood to reconstruct the micro-evolutionary response of trees to climate change and human forest management.
Subject(s)
DNA, Ancient/chemistry , Sequence Analysis, DNA/methods , Wood , Biodiversity , Biological Evolution , Climate Change , Forests , Quercus/geneticsABSTRACT
BACKGROUND: To date, genome-scale analyses in the domestic horse have been limited by suboptimal single nucleotide polymorphism (SNP) density and uneven genomic coverage of the current SNP genotyping arrays. The recent availability of whole genome sequences has created the opportunity to develop a next generation, high-density equine SNP array. RESULTS: Using whole genome sequence from 153 individuals representing 24 distinct breeds collated by the equine genomics community, we cataloged over 23 million de novo discovered genetic variants. Leveraging genotype data from individuals with both whole genome sequence, and genotypes from lower-density, legacy SNP arrays, a subset of ~5 million high-quality, high-density array candidate SNPs were selected based on breed representation and uniform spacing across the genome. Considering probe design recommendations from a commercial vendor (Affymetrix, now Thermo Fisher Scientific) a set of ~2 million SNPs were selected for a next-generation high-density SNP chip (MNEc2M). Genotype data were generated using the MNEc2M array from a cohort of 332 horses from 20 breeds and a lower-density array, consisting of ~670 thousand SNPs (MNEc670k), was designed for genotype imputation. CONCLUSIONS: Here, we document the steps taken to design both the MNEc2M and MNEc670k arrays, report genomic and technical properties of these genotyping platforms, and demonstrate the imputation capabilities of these tools for the domestic horse.
Subject(s)
Genotyping Techniques/methods , Horses/genetics , Oligonucleotide Array Sequence Analysis/methods , Polymorphism, Single Nucleotide , Animals , Gene Frequency , Genotyping Techniques/standards , Linkage Disequilibrium , Oligonucleotide Array Sequence Analysis/standards , Reference Standards , Whole Genome SequencingABSTRACT
The genomic changes underlying both early and late stages of horse domestication remain largely unknown. We examined the genomes of 14 early domestic horses from the Bronze and Iron Ages, dating to between ~4.1 and 2.3 thousand years before present. We find early domestication selection patterns supporting the neural crest hypothesis, which provides a unified developmental origin for common domestic traits. Within the past 2.3 thousand years, horses lost genetic diversity and archaic DNA tracts introgressed from a now-extinct lineage. They accumulated deleterious mutations later than expected under the cost-of-domestication hypothesis, probably because of breeding from limited numbers of stallions. We also reveal that Iron Age Scythian steppe nomads implemented breeding strategies involving no detectable inbreeding and selection for coat-color variation and robust forelimbs.
Subject(s)
Breeding , Domestication , Horses/genetics , Animals , DNA, Ancient , DNA, Mitochondrial/genetics , Genetic Variation , Genome , Neural Crest , Quantitative Trait, Heritable , Selection, GeneticABSTRACT
Ever since its emergence in 1984, the field of ancient DNA has struggled to overcome the challenges related to the decay of DNA molecules in the fossil record. With the recent development of high-throughput DNA sequencing technologies and molecular techniques tailored to ultra-damaged templates, it has now come of age, merging together approaches in phylogenomics, population genomics, epigenomics, and metagenomics. Leveraging on complete temporal sample series, ancient DNA provides direct access to the most important dimension in evolutiontime, allowing a wealth of fundamental evolutionary processes to be addressed at unprecedented resolution. This review taps into the most recent findings in ancient DNA research to present analyses of ancient genomic and metagenomic data.
Subject(s)
Biological Evolution , DNA, Ancient , Research/trends , Evolution, Molecular , Fossils , Genomics/trendsABSTRACT
The horse was domesticated only 5.5 KYA, thousands of years after dogs, cattle, pigs, sheep, and goats. The horse nonetheless represents the domestic animal that most impacted human history; providing us with rapid transportation, which has considerably changed the speed and magnitude of the circulation of goods and people, as well as their cultures and diseases. By revolutionizing warfare and agriculture, horses also deeply influenced the politico-economic trajectory of human societies. Reciprocally, human activities have circled back on the recent evolution of the horse, by creating hundreds of domestic breeds through selective programs, while leading all wild populations to near extinction. Despite being tightly associated with humans, several aspects in the evolution of the domestic horse remain controversial. Here, we review recent advances in comparative genomics and paleogenomics that helped advance our understanding of the genetic foundation of domestic horses.
Subject(s)
Animals, Domestic/genetics , Biological Evolution , Horses/genetics , Selective Breeding/genetics , Animals , Cattle , Dogs , HumansABSTRACT
The first epigenomes from archaic hominins (AH) and ancient anatomically modern humans (AMH) have recently been characterized, based, however, on a limited number of samples. The extent to which ancient genome-wide epigenetic landscapes can be reconstructed thus remains contentious. Here, we present epiPALEOMIX, an open-source and user-friendly pipeline that exploits post-mortem DNA degradation patterns to reconstruct ancient methylomes and nucleosome maps from shotgun and/or capture-enrichment data. Applying epiPALEOMIX to the sequence data underlying 35 ancient genomes including AMH, AH, equids and aurochs, we investigate the temporal, geographical and preservation range of ancient epigenetic signatures. We first assess the quality of inferred ancient epigenetic signatures within well-characterized genomic regions. We find that tissue-specific methylation signatures can be obtained across a wider range of DNA preparation types than previously thought, including when no particular experimental procedures have been used to remove deaminated cytosines prior to sequencing. We identify a large subset of samples for which DNA associated with nucleosomes is protected from post-mortem degradation, and nucleosome positioning patterns can be reconstructed. Finally, we describe parameters and conditions such as DNA damage levels and sequencing depth that limit the preservation of epigenetic signatures in ancient samples. When such conditions are met, we propose that epigenetic profiles of CTCF binding regions can be used to help data authentication. Our work, including epiPALEOMIX, opens for further investigations of ancient epigenomes through time especially aimed at tracking possible epigenetic changes during major evolutionary, environmental, socioeconomic, and cultural shifts.
Subject(s)
DNA Methylation , DNA, Ancient/analysis , High-Throughput Nucleotide Sequencing/methods , Nucleosomes/genetics , Sequence Analysis, DNA/methods , Chromatin Assembly and Disassembly , Computer Simulation , Cytosine/metabolism , DNA/genetics , Epigenesis, Genetic , Genome , Humans , SoftwareABSTRACT
BACKGROUND: As high-throughput sequencing platforms produce longer and longer reads, sequences generated from short inserts, such as those obtained from fossil and degraded material, are increasingly expected to contain adapter sequences. Efficient adapter trimming algorithms are also needed to process the growing amount of data generated per sequencing run. FINDINGS: We introduce AdapterRemoval v2, a major revision of AdapterRemoval v1, which introduces (i) striking improvements in throughput, through the use of single instruction, multiple data (SIMD; SSE1 and SSE2) instructions and multi-threading support, (ii) the ability to handle datasets containing reads or read-pairs with different adapters or adapter pairs, (iii) simultaneous demultiplexing and adapter trimming, (iv) the ability to reconstruct adapter sequences from paired-end reads for poorly documented data sets, and (v) native gzip and bzip2 support. CONCLUSIONS: We show that AdapterRemoval v2 compares favorably with existing tools, while offering superior throughput to most alternatives examined here, both for single and multi-threaded operations.
Subject(s)
Algorithms , High-Throughput Nucleotide Sequencing/methods , Base SequenceABSTRACT
As the oomycete pathogen causing potato late blight disease, Phytophthora infestans triggered the famous 19th-century Irish potato famine and remains the leading cause of global commercial potato crop destruction. But the geographic origin of the genotype that caused this devastating initial outbreak remains disputed, as does the New World center of origin of the species itself. Both Mexico and South America have been proposed, generating considerable controversy. Here, we readdress the pathogen's origins using a genomic data set encompassing 71 globally sourced modern and historical samples of P. infestans and the hybrid species P. andina, a close relative known only from the Andean highlands. Previous studies have suggested that the nuclear DNA lineage behind the initial outbreaks in Europe in 1845 is now extinct. Analysis of P. andina's phased haplotypes recovered eight haploid genome sequences, four of which represent a previously unknown basal lineage of P. infestans closely related to the famine-era lineage. Our analyses further reveal that clonal lineages of both P. andina and historical P. infestans diverged earlier than modern Mexican lineages, casting doubt on recent claims of a Mexican center of origin. Finally, we use haplotype phasing to demonstrate that basal branches of the clade comprising Mexican samples are occupied by clonal isolates collected from wild Solanum hosts, suggesting that modern Mexican P. infestans diversified on Solanum tuberosum after a host jump from a wild species and that the origins of P. infestans are more complex than was previously thought.