Biology subjects

Avila-Arcos, M. C.

Publications and source records attributed to Avila-Arcos, M. C..

13 recordsLinked to original sources

bioRxiv2026

Improving Local Ancestry Inference through Neural Networks

MotivationLocal Ancestry Inference (LAI) allows us to study evolutionary processes in admixed populations[1], uncover ancestry-specific disease risk factors[2], and to better understand the demographic history of these populations[3]. Many methods for LAI exist, however, these methods usually focus on cases of intercontinental admixture. In this work, we evaluate both existing and novel methods in challenging scenarios, such as downsampled reference panels, intracontinental admixture, and distant admixture events. ResultsWe present four novel LAI implementations based on neural network architectures, including Bidirectional Long Short-Term Memory and Transformer networks which have not previously been used for LAI. We compare these novel implementations to existing methods for LAI across a variety of scenarios using the 1 Thousand Genomes dataset and other synthetic datasets. We find that while all networks achieve high performance for intercontinental admixture scenarios, inference power is comparatively low for scenarios of intracontinental or distant admixture. We further show how our implementations achieve the best performance of all methods through specialized preprocessing and inference smoothing steps. AvailabilityAll implementations and benchmarking code available at https://github.com/Jazpy/LAINNs.

bioinformatics↗

bioRxiv2025

Ancient genomic insights into Salmonella enterica Paratyphi C in Central Mexico

Salmonella enterica is a widespread pathogen of major global health relevance, with over 2,500 serovars classified into non-typhoidal and typhoidal groups. Within the typhoidal group, S. enterica Paratyphi C causes paratyphoid fever in humans. Ancient DNA from this bacterium has previously been recovered from epidemic-associated burials in Eurasia and Mexico, dating back 6,000 to 300 years. Here, we analyzed dental DNA from seven individuals (radiocarbon dated to 1800-1940 CE) buried at the Temple of the Immaculate Conception in Mexico City, Central Mexico, and identified ancient S. enterica Paratyphi C DNA in a young female with Native American ancestry. Using an in-house targeted enrichment strategy and deep shotgun sequencing, we reconstructed a S. enterica Paratyphi C genome (COYC5) with [~]11X coverage. Phylogenetic and comparative genomic analyses place COYC5 in close association with previously reported S. enterica Paratyphi C genomes associated with the 1545 cocoliztli epidemic in southern Mexico, as well as with European strains. Divergence estimates indicate that the Mexican and European lineages shared a common ancestor approximately 1,400 years before present (yBP), reflecting an ancient evolutionary split predating European colonization of Mexico. In contrast, the divergence between COYC5 and the southern Mexican genomes occurred around 516 yBP, coinciding with the onset of the colonial period. This pattern supports a European introduction of S. enterica Paratyphi C during colonization, followed by its local diversification within Mexico. Despite this regional differentiation, the conserved presence of key virulence loci--such as SPI-7 and an active shufflon system--across COYC5, southern Mexican, and European genomes underscores the enduring pathogenic potential of S. enterica Paratyphi C. The identification of this bacterium in 19th-century Mexico City provides the first genomic evidence of its persistence in urban contexts beyond major epidemic outbreaks, offering new insights into its evolutionary trajectory in Mexico. These findings raise new questions about how the pathogen spread and persisted across different ecological, social, and epidemiological contexts in ancient Mexico and the Americas.

evolutionary biology↗

bioRxiv2025

Archaic ancestry inference in imputed ancient human genomes

When modern humans expanded from Africa into Eurasia, they interbred with archaic hominins such as Neanderthals and Denisovans. This groundbreaking discovery, made in part possible through the genomic analysis of archaic remains, reshaped our understanding of human origins, and opened new research avenues to study the effects and consequences of archaic introgression. While significant progress has been made in identifying and quantifying archaic introgression, most studies have focused on contemporary individual genomic data. As a result, relatively little is known about the evolution of archaic variants within modern human populations shortly after interbreeding occurred. While analysis of ancient DNA from modern humans offers the potential to address this scientific gap, its poor quality has hindered its exploration. However, recent studies have shown that imputation using contemporary reference panels can accurately infer missing genotypes in ancient genomes. Here, we investigate the feasibility of using imputation to improve both global and local archaic ancestry inference in ancient genomes, by downsampling to different low-coverage values and imputing 20 high-coverage (>10X) ancient genomes, representing individuals from diverse temporal and geographical contexts. We tested the reliability of detecting and quantifying archaic introgression using D-statistics and the f4-ratio. We identified consistent results from the imputed and the original ancient genomes, suggesting that genomic estimates to detect and quantify introgression work well in imputed genomes. Regarding Local Ancestry Inference we find that we can identify more introgressed segments in imputed genomes than in non-imputed genomes. Surprisingly, we find that imputation accuracy is even higher in regions of archaic ancestry compared to other regions of the genome, facilitating the detection of introgressed segments in imputed genomes. Imputation also allows detection of Denisovan segments in Siberian and Alaskan individuals. We show that segments identified even at 0.0625X coverage can be used to reconstruct the history of introgressed haplotypes. For example, comparisons with archaic segments in contemporary humans reveal that the oldest individual analyzed, UstIshim, carried segments that are now found exclusively in either European or East Eurasian populations, indicating that these segments co-occurred in a shared ancestral population. By comparing only ancient individuals, we demonstrate that clustering based solely on the identified archaic segments effectively groups individuals into genetic clusters that correspond to populations defined by geography and time. This analysis shows a clear distinction between individuals with Denisovan introgression and those without, as well as a more detailed separation between Mesolithic and Neolithic Europeans, with the latter closely resembling Central Eurasian individuals. Furthermore, despite the small sample size in this study, we are able to reconstruct the origins of genes identified as candidates for adaptive introgression in contemporary populations, such as the BCN2 gene, which is an adaptively introgressed gene identified in contemporary West Eurasians. Additionally, we identify new candidates for adaptive introgression including LEMD2 and MLN in Europe. In this gene-region, imputation helps resolve the introgressed haplotype, which is closest to the Vindija Neanderthal haplotype.

genomics↗

bioRxiv2025

An archaic reference-free method to jointly infer Neanderthal and Denisovan introgressed segments in modern human genomes

Admixture between populations is a common feature of human history. Admixture events introduce new genetic variation that can fuel evolution. Characterizing the significance of admixture events on the evolution of a population across various species is of great interest to evolutionary geneticists. Local Ancestry Inference (LAI) methods infer genetic ancestry of an individual at a particular chromosomal location. Certain methods specialize in detecting archaic introgression, which consists of interbreeding between modern and archaic humans like Neanderthals and Denisovans. Most current LAI methods allow the detection of a single archaic ancestry, and post-processing may distinguish between multiple waves of introgression. These methods vary in how they choose archaic or modern reference genomes for the inference. Here, we present a new HMM-based method (DAIseg), which has the advantage of simultaneously distinguishing between multiple waves of ancient and recent admixture, using only modern human reference genomes. Simulations demonstrate that DAIseg achieves higher overall performance than state-of-the-art methods. We also apply DAIseg to Papuan populations to jointly detect Denisovan and Neanderthal introgressed segments, and identify a higher number of archaic segments than previous methods. Analysis of inferred introgressed segments, shows that we can identify evidence for two Denisovan introgression events in Papuans without having any post-processing and filtering. Overall, on top of being able to deal with both Archaic and recent admixture, DAIseg provides a more principled approach for detecting and classifying Denisovan and Neanderthal segments which will improve downstream analysis of introgressed segments to infer the impact of archaic introgression in humans.

bioinformatics↗

bioRxiv2023

Simulation-based Benchmarking of Ancient Haplotype Inference for Detecting Population Structure

Paleogenomic data has informed us about the movements, growth, and relationships of ancient populations. It has also given us context for medically relevant adaptations that appear in present-day humans due to introgression from other hominids, and it continues to help us characterize the evolutionary history of humans. However, ancient DNA (aDNA) presents several practical challenges as various factors such as deamination, high fragmentation, environmental contamination of aDNA, and low amounts of recoverable endogenous DNA, make aDNA recovery and analysis more difficult than modern DNA. Most studies with aDNA leverage only SNP data, and only a few studies have made inferences on human demographic history based on haplotype data, possibly because haplotype estimation (or phasing) has not yet been systematically evaluated in the context of aDNA. Here, we evaluate how the unique challenges of aDNA can impact phasing quality. We also develop a software tool that simulates aDNA taking into account the features of aDNA as well as the evolutionary history of the population. We measured phasing error as a function of aDNA quality and demographic history, and found that low phasing error is achievable even for very ancient individuals ([~] 400 generations in the past) as long as contamination and read depth are adequate. Our results show that population splits or bottleneck events occurring between the reference and phased populations affect phasing quality, with bottlenecks resulting in the highest average error rates. Finally, we found that using estimated haplotypes, even if not completely accurate, is superior to using the simulated genotype data when reconstructing changes in population structure after population splits between present-day and ancient populations. AvailabilityAll software used for simulation and analysis is available at github.com/Jazpy/Paleogenomic-Datasim

bioinformatics↗

bioRxiv2023

The MUC19 gene in Denisovans, Neanderthals, and Modern Humans: An Evolutionary History of Recurrent Introgression and Natural Selection

We study the gene MUC19, for which some modern humans carry a Denisovan-like haplotype. MUC19 is a mucin, a glycoprotein that forms gels with various biological functions. We find diagnostic variants for the Denisovan-like MUC19 haplotype at high frequencies in admixed Latin American individuals, and at highest frequency in 23 ancient Indigenous American individuals, all predating population admixture with Europeans and Africans. We find that the Denisovan-like MUC19 haplotype is under positive selection and carries a higher copy number of a 30 base-pair variable number tandem repeat, and that copy numbers of this repeat are exceedingly high in American populations. Finally, some Neanderthals carry the Denisovan-like MUC19 haplotype, and that it was likely introgressed into human populations through Neanderthal introgression rather than Denisovan introgression. One-Sentence SummaryModern humans and Neanderthals carry a Denisovan variant of the MUC19 gene, which is under positive selection in populations of Indigenous American ancestry.

evolutionary biology↗

bioRxiv2022

Demographic history and genetic structure in pre-Hispanic Central Mexico

Aridoamerica and Mesoamerica are two distinct cultural areas that hosted numerous pre-Hispanic civilizations between 2,500 BCE and 1,521 CE. The division between these regions shifted southward due to severe droughts ca. 1,100 years ago, allegedly driving demographic changes and population replacement in some sites in central Mexico. Here, we present shotgun genome-wide data from 12 individuals and 26 mitochondrial genomes from eight pre-Hispanic archaeological sites across Mexico, including two at the shifting border of Aridoamerica and Mesoamerica. We find population continuity spanning the climate change episode and a broad preservation of the genetic structure across present-day Mexico for the last 2,300 years. Lastly, we identify a contribution to pre-Hispanic populations of northern and central Mexico from an ancient unsampled ghost population.

genomics↗

bioRxiv2022

Indigenous peoples in eastern Brazil: insights from 19th century genomes and metagenomes

Although Brazil was inhabited by more than 3,000 Indigenous populations prior to European colonization, todays Indigenous peoples represent less than 1% of Brazils census population. Some of the decimated communities belonged to the so-called "Botocudos" from central-eastern Brazil. These peoples are thought to represent a case of long-standing genetic continuity bearing a strong craniometric resemblance to that of the oldest Indigenous Americans ("Paleoamericans"). Yet, little is known about their origins and genetic relationship to other Native Americans, as only two "Botocudo" genomes have been sequenced so far and those were surprisingly of Polynesian ancestry. To deepen our knowledge on the genomic history of pre-contact Indigenous Americans and the pathogens they were exposed to, we carbon-dated and sequenced 24 ancient Brazilians (including 22 "Botocudos") whose remains were hosted at the National Museum of Rio de Janeiro and recovered prior to the tragic 2018 fire. The resulting genomes depth of coverage ranged from 0.001x to 24x. Their genetic ancestry was found to be Indigenous American without gene flow from external populations such as Europeans, Africans or Polynesians. Unlike Mesoamericans, the "Botocudos" and Amazonians do not seem to have experienced a population expansion once in the Americas. Moreover, remarkably, their genomes exhibit amongst the lowest levels of heterozygosity worldwide and long runs of homozygosity, which could be explained by unique social practices or a very small effective size. Finally, whole genomes of likely ancient pathogens were recovered, including lineages of Human parvovirus B19 that were possibly introduced after the European contact. Significance statementTo better understand the genetic relationship among Indigenous populations in Brazil, we sequenced the genomes of 24 ancient individuals (22 of which labelled as "Botocudos", a term used to describe hunter-gatherer tribes) whose remains were hosted at the Museu Nacional of Rio de Janeiro prior to the tragic fire that consumed it in 2018. Unlike two previously published "Botocudo" genomes, the 22 "Botocudos" from this study have Indigenous American-related ancestry without any Polynesian-related ancestry, and they are similarly related to several Native Brazilian populations. Finally, unlike Eurasian hunter-gatherers, the "Botocudos" exhibit among the lowest heterozygosity and longest runs of homozygosity worldwide - compatible with a very small effective size and suggesting a unique social structure among hunter-gatherers in the Americas.

genomics↗

bioRxiv2020

Ancient viral genomes reveal introduction of HBV and B19V to Mexico during the transatlantic slave trade.

After the European colonization of the Americas there was a dramatic population collapse of the Indigenous inhabitants caused in part by the introduction of new pathogens. Although there is much speculation on the etiology of the Colonial epidemics, direct evidence for the presence of specific viruses during the Colonial era is lacking. To uncover the diversity of viral pathogens during this period, we designed an enrichment assay targeting ancient DNA (aDNA) from viruses of clinical importance and applied it on DNA extracts from individuals found in a Colonial hospital and a Colonial chapel (16th c. - 18th c.) where records suggest victims of epidemics were buried during important outbreaks in Mexico City. This allowed us to reconstruct three ancient human parvovirus B19 genomes, and one ancient human hepatitis B virus genome from distinct individuals. The viral genomes are similar to African strains, consistent with the inferred morphological and genetic African ancestry of the hosts as well as with the isotopic analysis of the human remains, suggesting an origin on the African continent. This study provides direct molecular evidence of ancient viruses being transported to the Americas during the transatlantic slave trade and their subsequent introduction to New Spain. Altogether, our observations enrich the discussion about the etiology of infectious diseases during the Colonial period in Mexico.

genomics↗

bioRxiv2019

The genetic origins of Saint Helena’s liberated Africans

Between the early 16th and late 19th centuries, an estimated 12 million Africans were transported to the Americas as part of the transatlantic slave trade. Following Britains abolition of slave trade in 1807, the Royal Navy patrolled the Atlantic and intercepted slave ships that continued to operate. During this period, the island of St Helena in the middle of the South Atlantic served as a depot for \"liberated\" Africans. Between 1840 and 1867, approximately 27,000 Africans were disembarked on the island. To investigate their origins, we generated genome-wide ancient DNA data for 20 individuals recovered from St Helena. The genetic data indicate that they came from West Central Africa, possibly the area of present-day Gabon and Angola. The data further suggest that they did not belong to a single population, confirming historical reports of cultural heterogeneity among the islands African community. Our results shed new light on the origins of enslaved Africans during the final stages of the slave trade and illustrate how genetic data can be used to complement and validate existing historical sources.

genomics↗

bioRxiv2019

Population history and gene divergence in Native Mexicans inferred from 76 human exomes

Native American genetic variation remains underrepresented in most catalogs of human genome sequencing data. Previous genotyping efforts have revealed that Mexicos indigenous population is highly differentiated and substructured, thus potentially harboring higher proportions of private genetic variants of functional and biomedical relevance. Here we have targeted the coding fraction of the genome and characterized its full site frequency spectrum by sequencing 76 exomes from five indigenous populations across Mexico. Using diffusion approximations, we modeled the demographic history of indigenous populations from Mexico with northern and southern ethnic groups splitting 7.2 kya and subsequently diverging locally 6.5 kya and 5.7 kya, respectively. Selection scans for positive selection revealed BCL2L13 and KBTBD8 genes as potential candidates for adaptive evolution in Raramuris and Triquis, respectively. BCL2L13 is highly expressed in skeletal muscle and could be related to physical endurance, a well-known phenotype of the northern Mexico Raramuri. The KBTBD8 gene has been associated with idiopathic short stature and we found it to be highly differentiated in Triqui, a southern indigenous group from Oaxaca whose height is extremely low compared to other native populations.

genomics↗

bioRxiv2017

In-solution Y-chromosome capture-enrichment on ancient DNA libraries

BackgroundAs most ancient biological samples have low levels of endogenous DNA, it is advantageous to enrich for specific genomic regions prior to sequencing. One approach - in-solution capture-enrichment - retrieves sequences of interest and reduces the fraction of microbial DNA. In this work, we implement a capture-enrichment approach targeting informative regions of the Y chromosome in six human archaeological remains excavated in the Caribbean and dated between 200 and 3,000 years BP. We compare the recovery rate of Y-chromosome capture (YCC) alone, whole-genome capture followed by YCC (WGC+Y) versus non-enriched (pre-capture) libraries.\n\nResultsWe recovered 17-4,152 times more targeted unique Y-chromosome sequences after capture, where 0.01-6.2% (WGC+Y) and 0.01-23.5% (YCC) of the sequence reads were on-target, compared to 0.0002-0.004% pre-capture. In samples with endogenous DNA content greater than 0.1%, we found that WGC followed by YCC (WGC+Y) yields lower enrichment due to the loss of complexity in consecutive capture experiments, whereas in samples with lower endogenous content, WGC+Y yielded greater enrichment than YCC alone. Finally, increasing recovery of informative sites enabled us to assign Y-chromosome haplogroups to some of the archeological remains and gain insights about their paternal lineages and origins.\n\nConclusionsWe present to our knowledge the first in-solution capture-enrichment method targeting the human Y-chromosome in aDNA sequencing libraries. YCC and WGC+Y enrichments lead to an increase in the amount of Y-DNA sequences, as compared to libraries not enriched for the Y-chromosome. Our probe design effectively recovers regions of the Y-chromosome bearing phylogenetically informative sites, allowing us to identify paternal lineages with less sequencing than needed for pre-capture libraries. Finally we recommend considering the endogenous content in the experimental design and avoiding consecutive rounds of capture for low-complexity libraries, as clonality increases considerably with each round.

genomics↗

bioRxiv2017

Neolithization of North Africa involved the migration of people from both the Levant and Europe

The extent to which prehistoric migrations of farmers influenced the genetic pool of western North Africans remains unclear. Archaeological evidence suggests the Neolithization process may have happened through the adoption of innovations by local Epipaleolithic communities, or by demic diffusion from the Eastern Mediterranean shores or Iberia. Here, we present the first analysis of individuals genome sequences from early and late Neolithic sites in Morocco, as well as Early Neolithic individuals from southern Iberia. We show that Early Neolithic Moroccans are distinct from any other reported ancient individuals and possess an endemic element retained in present-day Maghrebi populations, confirming a long-term genetic continuity in the region. Among ancient populations, Early Neolithic Moroccans are distantly related to Levantine Natufian hunter-gatherers ([~]9,000 BCE) and Pre-Pottery Neolithic farmers ([~]6,500 BCE). Although an expansion in Early Neolithic times is also plausible, the high divergence observed in Early Neolithic Moroccans suggests a long-term isolation and an early arrival in North Africa for this population. This scenario is consistent with early Neolithic traditions in North Africa deriving from Epipaleolithic communities who adopted certain innovations from neighbouring populations. Late Neolithic ([~]3,000 BCE) Moroccans, in contrast, share an Iberian component, supporting theories of trans-Gibraltar gene flow. Finally, the southern Iberian Early Neolithic samples share the same genetic composition as the Cardial Mediterranean Neolithic culture that reached Iberia [~]5,500 BCE. The cultural and genetic similarities of the Iberian Neolithic cultures with that of North African Neolithic sites further reinforce the model of an Iberian migration into the Maghreb.\n\nSIGNIFICANCE STATEMENTThe acquisition of agricultural techniques during the so-called Neolithic revolution has been one of the major steps forward in human history. Using next-generation sequencing and ancient DNA techniques, we directly test if Neolithization in North Africa occurred through the transmission of ideas or by demic diffusion. We show that Early Neolithic Moroccans are composed of an endemic Maghrebi element still retained in present-day North African populations and distantly related to Epipaleolithic communities from the Levant. However, late Neolithic individuals from North Africa are admixed, with a North African and a European component. Our results support the idea that the Neolithization of North Africa might have involved both the development of Epipaleolithic communities and the migration of people from Europe.

genetics↗