Biology subjects

Veeramah, K. R.

Publications and source records attributed to Veeramah, K. R..

14 recordsLinked to original sources

bioRxiv2026

Genomic signatures of selection are enriched in differentially expressed genes in sticklebacks adapting to contrasting environments

Whole genome scans have identified numerous adaptive alleles in many species; however, linking these alleles to specific phenotypes remains a major challenge. A promising alternative to direct genotype-phenotype mapping, particularly given the complexities introduced by epistasis, pleiotropy, and environmental variability, is to assess whether differentially expressed genes are enriched in regions of genetic divergence between populations adapted to contrasting environments. Here, we study gene expression patterns in threespine stickleback populations adapting to contrasting environments (marine vs freshwater) and investigate how signatures of selection interact with patterns of gene expression. We performed transcriptomic experiments of the brain and gill tissues of wild-caught sticklebacks sampled from one marine and two freshwater environments using TagSeq. We found that differentially expressed genes in the freshwater environments are enriched for single nucleotide polymorphisms (SNPs) previously identified to be involved in rapid adaptation and FST outliers. A majority of these SNPs were located in cis-regulatory regions with predicted low to moderate effects on protein function and structure, although we found a high-impact SNP in the gene col8a1b. Genes such as pvalb4 and acsl4a, involved in calcium regulation in the gill and fatty acid metabolism in the brain, respectively, were enriched with SNPs showing signatures of selection. By linking signatures of selection to tissue-specific gene expression patterns, our study bridges the gap between genomic divergence and the molecular mechanisms underlying physiological adaptation to new environments. Significance StatementUnderstanding how genetic variation translates into adaptive traits remains a central challenge in evolutionary biology. While whole-genome scans routinely identify candidate adaptive alleles, connecting these variants to functional phenotypes is complicated by epistasis, pleiotropy, and environmental effects. Here, we integrate signatures of selection with tissue-specific gene expression in threespine stickleback adapting to contrasting environments (marine and freshwater). We demonstrate that differentially expressed genes in freshwater populations are enriched for previously identified adaptive SNPs and FST outliers, many of which are located in cis-regulatory regions with predicted low to moderate functional effects. Notably, we identify a high-impact variant leading to a premature stop codon in col8a1b and highlight genes such as pvalb4 and acsl4a that link selection to key physiological processes, including ion regulation in gills and fatty acid metabolism in the brain. By connecting genomic divergence to regulatory and tissue-specific expression changes, this work provides a mechanistic framework for understanding how natural selection shapes complex physiological adaptation.

evolutionary biology↗

bioRxiv2025

The shifting dynamics of ancestry and culture at a post-Roman crossroads

The collapse of the western Roman Empire in the 5th century created a period of geopolitical upheaval, driven by Barbarians dispersing into the former Empire and reshaping post-Roman communities. While there is now evidence for a major genetic impact of these migrations into specific regions of Europe, it is unknown whether these changes in ancestry were uniform across the continent. We investigate present-day Slovenia, a crucial crossroad connecting the Roman East and West and the gate to Italy during the Langobard invasion. We conducted paleogenomic and isotopic analyses of 410 individuals from 21 sites across Slovenia and Cividale (Italy), establishing a longitudinal transect, spanning eight centuries. During Late Antiquity, despite changes in burial artifacts, kinship practices, and settlement structures reflecting a shift in culture, we find high levels of genetic continuity with the local Late Roman population and reduced mobility. However, demographic turnover began during the 8th century, when communities with northeastern European ancestry and distinct cultural practices entered the region, gradually advancing westward over the span of three centuries, replacing the local populations. This shows that cultural change in post-Roman Europe could be decoupled from genetic change in transit zones, demonstrating a dynamic spatiotemporal process across the continent.

genetics↗

bioRxiv2025

Gene flow weakens genomic clines while selection maintains adaptive loci: two decades of evolution in Drosophila melanogaster natural populations

Spatial genetic clines suggest local adaptation, but whether they persist or erode over evolutionary time remains largely unknown. Here, we use a unique genomic time series collected over several decades to quantify how gene flow and selection jointly shape spatial genomic structure. We analyzed pooled whole-genome sequencing from 16 natural populations of Drosophila melanogaster sampled along the North American east coast between 1997 and 2023, spanning hundreds of generations. We find pronounced homogenization of populations over time, accompanied by a genome-wide loss of clinal variants. Polymorphisms that remained clinal were less steep on chromosome 3R, reflecting declines in the frequency and clinality of major chromosomal inversions. Genomic context modulates this process: clinal SNPs are preferentially lost in regions of high recombination, whereas remaining clines are increasingly concentrated in coding and splice-associated sites. Despite widespread erosion of spatial structure, we detect signatures of selection shared across space at detoxification loci, including cytochrome P450 genes linked to insecticide resistance. Together, our results show widespread homogenization of neutral spatial variation consistent with gene flow, while spatially varying selection has preserved a subset of functionally important loci.

evolutionary biology↗

bioRxiv2025

Unveiling the complexity of post-Roman polity formation using ancient DNA

The transformation of the Roman world (4th-9th centuries CE) culminating in the dissolution of the Western Roman Empire in the 5th century marked a fundamental transition in European history. "Barbarian" groups and Roman provincial societies merged into enduring political frameworks in some places but not in others. Key questions persist regarding the regionally specific nature of this transformation. Here, we present one of the most densely sampled early medieval datasets to date, enabling the reconstruction of a post-Roman polity at an unprecedented micro-regional resolution. Our integrated genetic and archaeological analysis of two Roman-period (n=68) and five post-Roman (n=246) sites from the Little Hungarian Plain, a former Roman frontier region, reveals a significant increase in Northern European genetic ancestry, likely reflecting a large-scale population movement into the region. Moreover, while all post-Roman sites, dated to the time of the Langobard Kingdom, share similar genetic profiles, burial practices, and material culture, they display distinct patterns of social organization, especially regarding the role that biological relatedness played in each community. Our results suggest that distinct social hierarchies might have existed between sites, and their intensive connectivity probably formed the basis for regional-level organisation within the post-Roman polity. Our study provides a framework for investigating how new polities take shape after the collapse of major political systems. Applied more broadly, this approach can deepen our understanding of societal transformation across early medieval Europe and beyond, offering a richer and more nuanced view of the human past than ever before.

evolutionary biology↗

bioRxiv2025

Rare Jackpot Individuals Drive Rapid Adaptation in Threespine Stickleback

Recombination has long been considered the primary mechanism to bring beneficial alleles together, which can increase the speed of adaptation from standing genetic variation. Recombination is fundamental to the transporter hypothesis proposed to explain precise parallel adaptation in Threespine Stickleback. We studied an instance of freshwater adaptation in the Threespine Stickleback system using whole genomic data from an evolutionary time series to observe the genomic dynamics underlying rapid parallel adaptation. Our experiment showed that rapid adaptation to a freshwater environment depended on a few individuals with large haploblocks of freshwater-adaptive alleles (jackpot carriers) present among the anadromous (i.e., sea-run) founders at low frequencies. Biological kinship analyses indicate that mating among jackpot carriers and between jackpot carriers and non-jackpot individuals led to a rapid increase in freshwater-adaptive alleles within the first few generations. This process allowed the population to overcome a substantial bottleneck likely caused by the low fitness of first-generation stickleback with a few freshwater-adaptive alleles born in the lake. Additionally, we found evidence that the genetic load that emerged from population growth after the bottleneck may have been reduced through an increase in homozygosity by inbreeding, ultimately purging deleterious alleles. Recombination likely played a limited role in this case of very rapid adaptation.

evolutionary biology↗

bioRxiv2022

Investigating community formation through dense spatial and temporal sampling of 5-6th century cemeteries in Pannonia

As the collapse of the Western Roman Empire accelerated during the 4th and 5th centuries, arriving "barbarian" groups began to establish new communities in the border provinces of the declining (and eventually former) empire. This was a time of significant cultural and political change throughout not only these border regions but Europe as a whole.1,2 To better understand post-Roman community formation in one of these key frontier zones after the collapse of the Hunnic movement, we generated new paleogenomic data for a set of 38 burials from a time series of three 5th century cemeteries3-5 at Lake Balaton, Hungary. We utilized a comprehensive sampling approach to characterize these cemeteries along with data from 38 additional burials from a previously published mid-6th century site6 and analyzed them alongside data from over 550 penecontemporaneous individuals7-19. The range of genetic diversity in all four of these local burial communities is extensive and wider ranging than penecontemporaneous Europeans sequenced to date. Despite many commonalities in burial representation and demography, we find that there were substantial differences in genetic ancestry between the sites. We detect evidence of northern European gene flow into the Lake Balaton region. Additionally, we observe a statistically significant association between dress artefacts and genetic ancestry among 5th century genetically female burials. Our analysis shows that the formation of early Medieval communities was a multifarious process even at a local level, consisting of genetically heterogeneous groups.

genetics↗

bioRxiv2022

A benchmarking of human Y-chromosomal haplogroup classifiers from whole-genome and whole-exome sequence data

The non-recombinant region of the Y chromosome (NRY) contains a great number of polymorphic markers that allows to accurately reconstruct pedigree relationships and retrieve ancestral information from study samples. The analysis of NRY is typically implemented in anthropological, medical, and forensic studies. High-throughput sequencing (HTS) has profoundly increased the identification of genetic markers in the NRY genealogy and has prompted the development of automated NRY haplogroup classification tools. Here, we present a benchmarking study of five command-line tools for NRY haplogroup classification. The evaluation was done using empirical short-read HTS data from 50 unrelated donors using paired data from whole-genome sequencing (WGS) and whole-exome sequencing (WES) experiments. Besides, we evaluate the performance of the top-ranked tool in the classification of data of third generation HTS obtained from a subset of donors. Our findings demonstrate that WES can be an efficient approach to infer the NRY haplogroup, albeit generally providing a lower level of genealogical resolution than that recovered by WGS. Among the tools evaluated, YLeaf offers the best performance for both WGS and WES applications. Finally, we demonstrate that YLeaf is able to correctly classify all samples sequenced with nanopore technology from long noisy reads.

genomics↗

bioRxiv2021

Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans

Microbial pathogens grow in a wide range of different morphologies that provide distinct advantages for virulence. In the fungal pathogen Candida albicans, adenylyl cyclase (Cyr1) is thought to be a master regulator of the switch to invasive hyphal morphogenesis and biofilm formation. However, faster growing cyr1{Delta}/{Delta} pseudorevertant (PR) mutants were identified that form hyphae in the absence of cAMP. Isolation of additional PR mutants revealed that their improved growth was due to loss of one copy of BCY1, the negative regulatory subunit of protein kinase (A) from the left arm of chromosome 2. Furthermore, hyphal morphogenesis was improved in some of PR mutants by multigenic haploinsufficiency resulting from loss of large regions of the left arm of chromosome 2, including global transcriptional regulators. Interestingly, hyphal-associated genes were also induced in a manner that was independent of cAMP. This indicates that basal protein kinase A activity is an important prerequisite to induce hyphae, but activation of the cAMP pathway is not needed. Instead, phosphoproteomic analysis indicated that the Cdc28 cyclin-dependent kinase and the casein kinase 1 family member Yck2 play key roles in promoting polarized growth. In addition, integrating transcriptomic and proteomic data reveals hyphal stimuli induce increased production of key transcription factors that contribute to polarized morphogenesis. AUTHOR SUMMARYThe human fungal pathogen Candida albicans switches between budding and filamentous hyphal morphologies to gain advantages for virulence and survival in the host. Although adenylyl cyclase has been thought to be a master regulator that controls this switch, we identified C. albicans pseudorevertant mutants that grow better and form hyphae in the absence of adenylyl cyclase and cAMP. The mutant cells were also able to induce hyphal-associated genes in the absence of cAMP that are needed for virulence. Integrating information from different omics approaches identified cAMP-independent mechanisms that promote hyphal growth. This includes phosphoproteomic studies that revealed key roles for the Cdc28 cyclin-dependent kinase and casein kinase 1 in promoting hyphal growth. In addition, integrating transcriptomic and proteomic data revealed that post-transcriptional mechanisms regulate the levels of a set of key transcription factors that are important for hyphal induction, suggesting a novel form of translational regulation. These studies better define the pathways that stimulate C. albicans to switch from budding to hyphal growth, which is important for invasion into tissues, escape from the immune system, and biofilm formation.

microbiology↗

bioRxiv2020

Predicting future from past: The genomic basis of recurrent and rapid stickleback evolution

Similar forms often evolve repeatedly in nature, raising longstanding questions about the underlying mechanisms. Here we use repeated evolution in sticklebacks to identify a large set of genomic loci that change recurrently during colonization of new freshwater habitats by marine fish. The same loci used repeatedly in extant populations also show rapid allele frequency changes when new freshwater populations are experimentally established from marine ancestors. Dramatic genotypic and phenotypic changes arise within 5-7 years, facilitated by standing genetic variation and linkage between adaptive regions. Both the speed and location of changes can be predicted using empirical observations of recurrence in natural populations or fundamental genomic features like allelic age, recombination rates, density of divergent loci, and overlap with mapped traits. A composite model trained on these stickleback features can also predict the location of key evolutionary loci in Darwins finches, suggesting similar features are important for evolution across diverse taxa.

evolutionary biology↗

bioRxiv2020

Florida Drosophila melanogaster genomes sampled 13 years apart show increases in warm-associated SNP alleles

We studied genetic change in Drosophila melanogaster using whole-genome SNP data from samples taken 13 years apart in Homestead, FL. This population is at the southern tip of a well-studied US latitudinal cline. On the non-inversion-carrying chromosome arms, 11-16% of SNPs show significant frequency changes. These are enriched for latitudinal clines and genic sites. For clinal SNPs each allele is either the northern- or southern-favored. Seventy-eight to 95 percent with significant frequency increase are southern-favored. Five to seven percent of SNPs also show significant seasonal change and involve increases in the northern-favored allele during the season. On the 2L and 3R chromosome arms there are significant seasonal shifts for common inversions. We identify regions and genes that are candidates for selection. These regions also show correspondence with those associated with soft sweeps in Raleigh, NC. This shift towards southern-favored alleles may be caused by climate shifts or increased African-European admixture.

evolutionary biology↗

bioRxiv2020

Kinship, acquired and inherited status, and population structure at the Early Bronze Age Mokrin necropolis in northern Serbia.

Twenty-four ancient genomes with an average sequencing coverage of 0.85{+/-}0.25 X were produced from the Mokrin necropolis, an Early Bronze Age (2,100-1,800 BC) Maros culture site in Serbia, to provide unambiguous identification of biological sex, population structure, and genetic kinship between individuals. Of the 24 investigated individuals, 15 were involved in kinship relationships of varying degrees, including 3 parent-offspring relationships. All observed parent-offspring pairs were mother and son. In addition to the absence of biological daughters, we observed a number of young women and girls with no biological relatives in our sample. These observations, together with the high mitochondrial diversity in our sample, are consistent with the practice of female exogamy in the population served by Mokrin. However, moderate-to-high Y-chromosomal diversity suggests a degree of male mobility greater than that expected under strict patrilocality. Individual status differences at Mokrin, as indicated by grave goods, support the inference that females could inherit status, but could not transmit status to all their sons. The case of a son whose grave good richness outstrips that of his biological mother suggests that sons had the possibility to acquire status during their lifetimes. The Mokrin sample resembles a genetically unstructured population, suggesting that the communitys social hierarchies were not accompanied by strict marriage barriers.

genomics↗

bioRxiv2019

Co-option of the gibbon-specific LAVA retrotransposon in DNA repair pathways

Co-option of transposable elements (TEs) to become part of existing or new enhancers is an important mechanism for evolution of gene regulation. However, contributions of lineage-specific TE insertions to recent regulatory adaptations remain poorly understood. Gibbons present a suitable model to study these contributions as they have evolved a lineage-specific TE called LAVA, which is still active in the gibbon genome. The LAVA retrotransposon is thought to have played a role in the emergence of the unusually rearranged structure of the gibbon genome by disrupting transcription of cell cycle genes. In this study, we investigated whether LAVA may have also contributed to the evolution of gene regulation by adopting enhancer function. We characterized fixed and polymorphic LAVA insertions across multiple gibbons and found 96 LAVA elements overlapping enhancer chromatin states. Moreover, LAVA was enriched in multiple transcription factor binding motifs, was bound by an important transcription factor (PU.1), and was associated with higher levels of gene expression in cis. We found gibbon-specific signatures of purifying/positive selection at 27 LAVA insertions. Two of these insertions were fixed in the gibbon lineage and overlapped with enhancer chromatin states, representing putative co-opted LAVA enhancers. These putative enhancers were located within genes encoding SETD2 and RAD9A, two proteins that facilitate accurate repair of DNA double-strand breaks and prevent chromosomal rearrangement mutations. Thus, LAVAs co-option in these genes may have influenced regulation of processes that preserve genome integrity. Our findings highlight the importance of considering lineage-specific TEs in studying evolution of novel gene regulatory elements.

evolutionary biology↗

bioRxiv2018

Understanding 6th-Century Barbarian Social Organization and Migration through Paleogenomics

ABSTARCTDespite centuries of research, much about the barbarian migrations that took place between the fourth and sixth centuries in Europe remains hotly debated. To better understand this key era that marks the dawn of modern European societies, we obtained ancient genomic DNA from 63 samples from two cemeteries (from Hungary and Northern Italy) that have been previously associated with the Longobards, a barbarian people that ruled large parts of Italy for over 200 years after invading from Pannonia in 568 CE. Our dense cemetery-based sampling revealed that each cemetery was primarily organized around one large pedigree, suggesting that biological relationships played an important role in these early Medieval societies. Moreover, we identified genetic structure in each cemetery involving at least two groups with different ancestry that were very distinct in terms of their funerary customs. Finally, our data was consistent with the proposed long-distance migration from Pannonia to Northern Italy.

genetics↗

bioRxiv2017

Selective sweep analysis using village dogs highlights the pivotal role of the neural crest in dog domestication

BackgroundDogs (Canis lupus familiaris) were domesticated from gray wolves between 10-40 kya in Eurasia, yet details surrounding the process of domestication remain unclear. The vast array of phenotypes exhibited by dogs mirror other domesticated animal species, a phenomenon known as the Domestication Syndrome. Here, we use signatures persisting in the dog genome to identify genes and pathways altered by the intensive selective pressures of domestication.\n\nResultsWe identified 246 candidate domestication regions containing 10.8Mb of genome sequence and 178 genes through whole-genome SNP analysis of 43 globally distributed village dogs and 10 wolves. Comparisons with ancient dog genomes suggest that these regions reflect signatures of domestication rather than breed formation. The strongest hit is located in the Retinoic Acid-Induced 1 (RAI1) gene, mutations of which cause Smith-Magenis syndrome. The identified regions contain a significant enrichment of genes linked to neural crest cell migration, differentiation and development. Read depth analysis suggests that copy number variation played a minor role in dog domestication.\n\nConclusionOur results indicate that phenotypes distinguishing domesticated dogs from wolves, such as tameness, smaller jaws, floppy ears, and diminished craniofacial development, are determined by genes which act early in embryogenesis. These differences are all phenotypes of the Domestication Syndrome, which can be explained by decreases in neural crest cells at these sites. We propose that initial selection during early dog domestication was for behavior, a trait also influenced by genes which act in the neural crest, which secondarily gave rise to the phenotypes of modern dogs.

evolutionary biology↗