ORCID Profile
0000-0003-1936-0236
Current Organisation
University of Otago
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Gene Expression (incl. Microarray and other genome-wide approaches) | Genome Structure and Regulation | Aboriginal and Torres Strait Islander History | Genetics | Anthropological Genetics | Biogeography and Phylogeography | Evolutionary Biology | Biological Adaptation
Expanding Knowledge in the Biological Sciences | Understanding Australia's Past | Understanding Past Societies not elsewhere classified | Conserving Aboriginal and Torres Strait Islander Heritage |
Publisher: Cold Spring Harbor Laboratory
Date: 13-03-2015
Abstract: It is commonly thought that human genetic ersity in non-African populations was shaped primarily by an out-of-Africa dispersal 50–100 thousand yr ago (kya). Here, we present a study of 456 geographically erse high-coverage Y chromosome sequences, including 299 newly reported s les. Applying ancient DNA calibration, we date the Y-chromosomal most recent common ancestor (MRCA) in Africa at 254 (95% CI 192–307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47–52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.
Publisher: Springer Science and Business Media LLC
Date: 18-09-2019
DOI: 10.1038/S41590-019-0492-0
Abstract: Resisting and tolerating microbes are alternative strategies to survive infection, but little is known about the evolutionary mechanisms controlling this balance. Here genomic analyses of anatomically modern humans, extinct Denisovan hominins and mice revealed a TNFAIP3 allelic series with alterations in the encoded immune response inhibitor A20. Each TNFAIP3 allele encoded substitutions at non-catalytic residues of the ubiquitin protease OTU domain that diminished IκB kinase-dependent phosphorylation and activation of A20. Two TNFAIP3 alleles encoding A20 proteins with partial phosphorylation deficits seemed to be beneficial by increasing immunity without causing spontaneous inflammatory disease: A20 T108A I207L, originating in Denisovans and introgressed in modern humans throughout Oceania, and A20 I325N, from an N-ethyl-N-nitrosourea (ENU)-mutagenized mouse strain. By contrast, a rare human TNFAIP3 allele encoding an A20 protein with 95% loss of phosphorylation, C243Y, caused spontaneous inflammatory disease in humans and mice. Analysis of the partial-phosphorylation A20 I325N allele in mice revealed diminished tolerance of bacterial lipopolysaccharide and poxvirus inoculation as tradeoffs for enhanced immunity.
Publisher: The Royal Society
Date: 08-2019
DOI: 10.1098/RSOS.190733
Abstract: Population genetics has been successful at identifying the relationships between human groups and their interconnected histories. However, the link between genetic demography inferred at large scales and the in idual human behaviours that ultimately generate that demography is not always clear. While anthropological and historical context are routinely presented as adjuncts in population genetic studies to help describe the past, determining how underlying patterns of human sociocultural behaviour impact genetics still remains challenging. Here, we analyse patterns of genetic variation in village-scale s les from two islands in eastern Indonesia, patrilocal Sumba and a matrilocal region of Timor. Adopting a ‘process modelling’ approach, we iteratively explore combinations of structurally different models as a thinking tool. We find interconnected socio-genetic interactions involving sex-biased migration, lineage-focused founder effects, and on Sumba, heritable social dominance. Strikingly, founder ideology, a cultural model derived from anthropological and archaeological studies at larger regional scales, has both its origins and impact at the scale of villages. Process modelling lets us explore these complex interactions, first by circumventing the complexity of formal inference when studying large datasets with many interacting parts, and then by explicitly testing complex anthropological hypotheses about sociocultural behaviour from a more familiar population genetic standpoint.
Publisher: Cold Spring Harbor Laboratory
Date: 09-07-2020
DOI: 10.1101/2020.07.09.196444
Abstract: Modern humans have substantially admixed with multiple archaic hominins. Papuans, in particular, owe up to 5% of their genome to Denisovans, a sister group to Neanderthals, whose remains have only been identified in Siberia and Tibet. Unfortunately, the biological and evolutionary significance of these introgression events remain poorly understood. Here we investigate the function of archaic alleles of both Denisovan and Neanderthal ancestry characterised within a previously published set of 56 genomes from in iduals of Papuan genetic ancestry living in the island of New Guinea. By comparing the distribution of archaic and modern human variants, we are able to assess the consequences of archaic admixture across a multitude of different cell types and functional elements. We detect a consistent signal across Denisovan variants of strong involvement in immune-related processes throughout our analyses. Archaic alleles are often located within cis-regulatory elements and transcribed regions of the genome, suggesting that they are capable of contributing to a wide range of cellular regulatory processes. We identify 3,538 high-confidence Denisovan variants that fall within annotated cis-regulatory elements and have the potential to alter the affinity of multiple transcription factors to their cognate DNA motifs, highlighting a likely mechanism by which introgressed DNA can impact phenotypes in present-day humans. Lastly, we experimentally validate these predictions by testing the regulatory potential of five Denisovan variants segregating at high frequency within Papuan in iduals, and find that two are associated with a significant reduction of transcriptional activities in plasmid reporter assays relative to modern human alleles. Together, these data provide support for the hypothesis that, despite their broadly deleterious nature, archaic alleles actively contribute to modern human phenotypic ersity to this day, and might have facilitated early adaptation to non-African environments.
Publisher: Springer Science and Business Media LLC
Date: 29-01-2018
DOI: 10.1038/S41598-018-20026-8
Abstract: The debate concerning the origin of the Polynesian speaking peoples has been recently reinvigorated by genetic evidence for secondary migrations to western Polynesia from the New Guinea region during the 2nd millennium BP. Using genome-wide autosomal data from the Leeward Society Islands, the ancient cultural hub of eastern Polynesia, we find that the inhabitants’ genomes also demonstrate evidence of this episode of admixture, dating to 1,700–1,200 BP. This supports a late settlement chronology for eastern Polynesia, commencing ~1,000 BP, after the internal differentiation of Polynesian society. More than 70% of the autosomal ancestry of Leeward Society Islanders derives from Island Southeast Asia with the lowland populations of the Philippines as the single largest potential source. These long-distance migrants into Polynesia experienced additional admixture with northern Melanesians prior to the secondary migrations of the 2nd millennium BP. Moreover, the genetic ersity of mtDNA and Y chromosome lineages in the Leeward Society Islands is consistent with linguistic evidence for settlement of eastern Polynesia proceeding from the central northern Polynesian outliers in the Solomon Islands. These results stress the complex demographic history of the Leeward Society Islands and challenge phylogenetic models of cultural evolution predicated on eastern Polynesia being settled from Samoa.
Publisher: Springer Science and Business Media LLC
Date: 11-11-2020
Publisher: Oxford University Press (OUP)
Date: 12-05-2015
Publisher: Springer Science and Business Media LLC
Date: 2011
Publisher: Wiley
Date: 15-02-2020
DOI: 10.1111/MPP.12913
Publisher: Cold Spring Harbor Laboratory
Date: 23-03-2022
DOI: 10.1101/2022.03.22.482717
Abstract: Scab, caused by the biotrophic fungus Venturia inaequalis , is the most economically important disease of apples worldwide. During infection, V. inaequalis occupies the subcuticular environment, where it secretes virulence factors, termed effectors, to promote host colonization. Consistent with other plant-pathogenic fungi, many of these effectors are expected to be non-enzymatic proteins, some of which can be recognized by corresponding host resistance proteins to activate plant defences, thus acting as avirulence determinants. To develop durable control strategies against scab, a better understanding of the roles that these effector proteins play in promoting subcuticular growth by V. inaequalis , as well as in activating, suppressing or circumventing resistance protein-mediated defences in apple, is required. We generated the first comprehensive RNA-seq transcriptome of V. inaequalis during colonization of apple. Analysis of this transcriptome revealed five temporal waves of gene expression that peaked during early, mid or mid-late infection. While the number of genes encoding secreted, non-enzymatic proteinaceous effector candidates (ECs) varied in each wave, most belonged to waves that peaked in expression during mid-late infection. Spectral clustering based on sequence similarity determined that the majority of ECs belonged to expanded protein families. To gain insights into function, the tertiary structures of ECs were predicted using AlphaFold2. Strikingly, despite an absence of sequence similarity, many ECs were predicted to have structural similarity to avirulence proteins from other plant-pathogenic fungi, including members of the MAX, LARS, ToxA and FOLD effector families. In addition, several other ECs, including an EC family with sequence similarity to the AvrLm6 avirulence effector from Leptosphaeria maculans , were predicted to adopt a KP6-like fold. Thus, proteins with a KP6-like fold represent another structural family of effectors shared among plant-pathogenic fungi. Our study reveals the transcriptomic profile underpinning subcuticular growth by V. inaequalis and provides an enriched list of ECs that can be investigated for roles in virulence and avirulence. Furthermore, our study supports the idea that numerous sequence-unrelated effectors across plant-pathogenic fungi share common structural folds. In doing so, our study gives weight to the hypothesis that many fungal effectors evolved from ancestral genes through duplication, followed by sequence ersification, to produce sequence-unrelated but structurally similar proteins.
Publisher: Cold Spring Harbor Laboratory
Date: 24-07-2020
DOI: 10.1101/2020.07.24.219048
Abstract: The hominin fossil record of Island Southeast Asia (ISEA) indicates that at least two endemic ‘super-archaic’ species – Homo luzonensis and H. floresiensis – were present around the time anatomically modern humans (AMH) arrived in the region ,000 years ago. Contemporary human populations carry signals consistent with interbreeding events with Denisovans in ISEA – a species that is thought to be more closely related to AMH than the super-archaic endemic ISEA hominins. To query this disparity between fossil and genetic evidence, we performed a comprehensive search for super-archaic introgression in modern human genomes. Our results corroborate widespread Denisovan ancestry in ISEA populations but fail to detect any super-archaic admixture signals. By highlighting local megafaunal survival east of the Wallace Line as a potential signature of deep, pre- H. sapiens hominin-faunal interaction, we propose that this understudied region may hold the key to unlocking significant chapters in Denisovan prehistory.
Publisher: Wiley
Date: 24-05-2021
Abstract: Some Serratia entomophila isolates have been successfully exploited in biopesticides due to their ability to cause amber disease in larvae of the Aotearoa (New Zealand) endemic pasture pest, Costelytra giveni . Anti‐feeding prophage and ABC toxin complex virulence determinants are encoded by a 153‐kb single‐copy conjugative plasmid (pADAP a mber d isease‐ a ssociated p lasmid). Despite growing understanding of the S . entomophila pADAP model plasmid, little is known about the wider plasmid family. Here, we sequence and analyse mega‐plasmids from 50 Serratia isolates that induce variable disease phenotypes in the C . giveni insect host. Mega‐plasmids are highly conserved within S . entomophila , but show considerable ergence in Serratia proteamaculans with other variants in S . liquefaciens and S . marcescens , likely reflecting niche adaption. In this study to reconstruct ancestral relationships for a complex mega‐plasmid system, strong co‐evolution between Serratia species and their plasmids were found. We identify 12 distinct mega‐plasmid genotypes, all sharing a conserved gene backbone, but encoding highly variable accessory regions including virulence factors, secondary metabolite biosynthesis, Nitrogen fixation genes and toxin‐antitoxin systems. We show that the variable pathogenicity of Serratia isolates is largely caused by presence/absence of virulence clusters on the mega‐plasmids, but notably, is augmented by external chromosomally encoded factors.
Publisher: Cold Spring Harbor Laboratory
Date: 03-04-2020
DOI: 10.1101/2020.04.01.021006
Abstract: The role of natural selection in shaping biological ersity is an area of intense interest in modern biology. To date, studies of positive selection have primarily relied upon genomic datasets from contemporary populations, which are susceptible to confounding factors associated with complex and often unknown aspects of population history. In particular, admixture between erged populations can distort or hide prior selection events in modern genomes, though this process is not explicitly accounted for in most selection studies despite its apparent ubiquity in humans and other species. Through analyses of ancient and modern human genomes, we show that previously reported Holocene-era admixture has masked more than 50 historic hard sweeps in modern European genomes. Our results imply that this canonical mode of selection has likely been underappreciated in the evolutionary history of humans and suggests that our current understanding of the tempo and mode of selection in natural populations may be quite inaccurate.
Publisher: Public Library of Science (PLoS)
Date: 26-05-2020
Publisher: Scientific Societies
Date: 03-2015
DOI: 10.1094/MPMI-09-14-0293-FI
Abstract: Beneficial plant–fungal interactions play an important role in the ability of plants to survive changing environmental conditions. In contrast, phytopathogenic fungi fall at the opposite end of the symbiotic spectrum, causing reduced host growth or even death. In order to exploit beneficial interactions and prevent pathogenic ones, it is essential to understand the molecular differences underlying these alternative states. The association between the endophyte Epichloë festucae and Lolium perenne (perennial ryegrass) is an excellent system for studying these molecular patterns due to the existence of several fungal mutants that have an antagonistic rather than a mutualistic interaction with the host plant. By comparing gene expression in a wild-type beneficial association with three mutant antagonistic associations disrupted in key signaling genes, we identified a core set of 182 genes that show common differential expression patterns between these two states. These gene expression changes are indicative of a nutrient-starvation response, as supported by the upregulation of genes encoding degradative enzymes, transporters, and primary metabolism, and downregulation of genes encoding putative small-secreted proteins and secondary metabolism. These results suggest that disruption of a mutualistic symbiotic interaction may lead to an elevated uptake and degradation of host-derived nutrients and cell-wall components, reminiscent of phytopathogenic interactions.
Publisher: Public Library of Science (PLoS)
Date: 08-12-2022
DOI: 10.1371/JOURNAL.PGEN.1010470
Abstract: Modern humans have admixed with multiple archaic hominins. Papuans, in particular, owe up to 5% of their genome to Denisovans, a sister group to Neanderthals whose remains have only been identified in Siberia and Tibet. Unfortunately, the biological and evolutionary significance of these introgression events remain poorly understood. Here we investigate the function of both Denisovan and Neanderthal alleles characterised within a set of 56 genomes from Papuan in iduals. By comparing the distribution of archaic and non-archaic variants we assess the consequences of archaic admixture across a multitude of different cell types and functional elements. We observe an enrichment of archaic alleles within cis-regulatory elements and transcribed regions of the genome, with Denisovan variants strongly affecting elements active within immune-related cells. We identify 16,048 and 10,032 high-confidence Denisovan and Neanderthal variants that fall within annotated cis-regulatory elements and with the potential to alter the affinity of multiple transcription factors to their cognate DNA motifs, highlighting a likely mechanism by which introgressed DNA can impact phenotypes. Lastly, we experimentally validate these predictions by testing the regulatory potential of five Denisovan variants segregating within Papuan in iduals, and find that two are associated with a significant reduction of transcriptional activity in plasmid reporter assays. Together, these data provide support for a widespread contribution of archaic DNA in shaping the present levels of modern human genetic ersity, with different archaic ancestries potentially affecting multiple phenotypic traits within non-Africans.
Publisher: Cold Spring Harbor Laboratory
Date: 16-07-2019
DOI: 10.1101/704304
Abstract: Indonesia is the world’s fourth most populous country, host to striking levels of human ersity, regional patterns of admixture, and varying degrees of introgression from both Neanderthals and Denisovans. However, it has been largely excluded from the human genomics sequencing boom of the last decade. To serve as a benchmark dataset of molecular phenotypes across the region, we generated genome-wide CpG methylation and gene expression measurements in over 100 in iduals from three locations that capture the major genomic and geographical axes of ersity across the Indonesian archipelago. Investigating between- and within-island differences, we find up to 10% of tested genes are differentially expressed between the islands of Mentawai (Sumatra) and New Guinea. Variation in gene expression is closely associated with DNA methylation, with expression levels of 9.7% of genes strongly correlating with nearby CpG methylation, and many of these genes being differentially expressed between islands. Genes identified in our differential expression and methylation analyses are enriched in pathways involved in immunity, highlighting Indonesia tropical role as a source of infectious disease ersity and the strong selective pressures these diseases have exerted on humans. Finally, we identify robust within-island variation in DNA methylation and gene expression, likely driven by very local environmental differences across s ling sites. Together, these results strongly suggest complex relationships between DNA methylation, transcription, archaic hominin introgression and immunity, all jointly shaped by the environment. This has implications for the application of genomic medicine, both in critically understudied Indonesia and globally, and will allow a better understanding of the interacting roles of genomic and environmental factors shaping molecular and complex phenotypes.
Publisher: Springer Science and Business Media LLC
Date: 08-04-2021
DOI: 10.1038/S41586-021-03473-8
Abstract: A Correction to this paper has been published: 0.1038/s41586-021-03473-8.
Publisher: Springer Science and Business Media LLC
Date: 2013
Publisher: Springer Science and Business Media LLC
Date: 28-08-2023
Publisher: Cold Spring Harbor Laboratory
Date: 24-10-2022
DOI: 10.1101/2022.10.22.513130
Abstract: The kākāpō is a critically endangered, intensively managed, long-lived nocturnal parrot endemic to Aotearoa New Zealand. We generated and analyzed whole-genome sequence data for nearly all in iduals living in early 2018 (169 in iduals) to generate a high-quality species-wide genetic variant callset. We leverage extensive long-term metadata to quantify genome-wide ersity of the species over time and present new approaches using probabilistic programming, combined with a phenotype dataset spanning five decades, to disentangle phenotypic variance into environmental and genetic effects while quantifying uncertainty in small populations. We find associations for growth, disease susceptibility, clutch size, and egg fertility within genic regions previously shown to influence these traits in other species. Finally, we generate breeding values to predict phenotype and illustrate that active management over the past 45 years has maintained both genome-wide ersity and ersity in breeding values, and hence, evolutionary potential. We provide new pathways for informing future conservation management decisions for kākāpō, including prioritizing in iduals for translocation and monitoring in iduals with poor growth or high disease risk. Overall, by explicitly addressing the challenge of small s le size, we provide a template for the inclusion of genomic data that will be transformational for species recovery efforts around the globe.
Publisher: Cold Spring Harbor Laboratory
Date: 25-09-2020
DOI: 10.1101/2020.09.25.313726
Abstract: Lack of ersity in human genomics limits our understanding of the genetic underpinnings of complex traits, hinders precision medicine, and contributes to health disparities. To map genetic effects on gene regulation in the underrepresented Indonesian population, we have integrated genotype, gene expression, and CpG methylation data from 115 participants across three island populations that capture the major sources of genomic ersity on the region. In a comparison with a European dataset, we identify 166 uniquely Indonesia-specific eQTLs, highlighting the benefits of performing association studies on non-European populations. By combining local ancestry and archaic introgression inference eQTLs and methylQTLs, we identify regulatory loci driven by modern Papuan ancestry as well as introgressed Denisovan and Neanderthal variation. GWAS colocalization connects QTLs detected here to hematological traits. Our findings illustrate how local ancestry and archaic introgression drive variation in gene regulation across genetically distinct and in admixed populations.
Publisher: Springer Science and Business Media LLC
Date: 12-10-2015
Publisher: Springer Science and Business Media LLC
Date: 03-11-2022
DOI: 10.1186/S12915-022-01442-9
Abstract: Scab, caused by the biotrophic fungus Venturia inaequalis , is the most economically important disease of apples worldwide. During infection, V. inaequalis occupies the subcuticular environment, where it secretes virulence factors, termed effectors, to promote host colonization. Consistent with other plant-pathogenic fungi, many of these effectors are expected to be non-enzymatic proteins, some of which can be recognized by corresponding host resistance proteins to activate plant defences, thus acting as avirulence determinants. To develop durable control strategies against scab, a better understanding of the roles that these effector proteins play in promoting subcuticular growth by V. inaequalis , as well as in activating, suppressing, or circumventing resistance protein-mediated defences in apple, is required. We generated the first comprehensive RNA-seq transcriptome of V. inaequalis during colonization of apple. Analysis of this transcriptome revealed five temporal waves of gene expression that peaked during early, mid, or mid-late infection. While the number of genes encoding secreted, non-enzymatic proteinaceous effector candidates (ECs) varied in each wave, most belonged to waves that peaked in expression during mid-late infection. Spectral clustering based on sequence similarity determined that the majority of ECs belonged to expanded protein families. To gain insights into function, the tertiary structures of ECs were predicted using AlphaFold2. Strikingly, despite an absence of sequence similarity, many ECs were predicted to have structural similarity to avirulence proteins from other plant-pathogenic fungi, including members of the MAX, LARS, ToxA and FOLD effector families. In addition, several other ECs, including an EC family with sequence similarity to the AvrLm6 avirulence effector from Leptosphaeria maculans , were predicted to adopt a KP6-like fold. Thus, proteins with a KP6-like fold represent another structural family of effectors shared among plant-pathogenic fungi. Our study reveals the transcriptomic profile underpinning subcuticular growth by V. inaequalis and provides an enriched list of ECs that can be investigated for roles in virulence and avirulence. Furthermore, our study supports the idea that numerous sequence-unrelated effectors across plant-pathogenic fungi share common structural folds. In doing so, our study gives weight to the hypothesis that many fungal effectors evolved from ancestral genes through duplication, followed by sequence ersification, to produce sequence-unrelated but structurally similar proteins.
Publisher: Wiley
Date: 25-08-2015
DOI: 10.1111/NPH.13614
Abstract: Beneficial associations between plants and microbes play an important role in both natural and agricultural ecosystems. For ex le, associations between fungi of the genus Epichloë , and cool‐season grasses are known for their ability to increase resistance to insect pests, fungal pathogens and drought. However, little is known about the molecular changes induced by endophyte infection. To study the impact of endophyte infection, we compared the expression profiles, based on RNA sequencing, of perennial ryegrass infected with Epichloë festucae with noninfected plants. We show that infection causes dramatic changes in the expression of over one third of host genes. This is in stark contrast to mycorrhizal associations, where substantially fewer changes in host gene expression are observed, and is more similar to pathogenic interactions. We reveal that endophyte infection triggers reprogramming of host metabolism, favouring secondary metabolism at a cost to primary metabolism. Infection also induces changes in host development, particularly trichome formation and cell wall biogenesis. Importantly, this work sheds light on the mechanisms underlying enhanced resistance to drought and super‐infection by fungal pathogens provided by fungal endophyte infection. Finally, our study reveals that not all beneficial plant–microbe associations behave the same in terms of their effects on the host.
Publisher: Springer Science and Business Media LLC
Date: 22-03-2021
Publisher: Elsevier BV
Date: 2022
Start Date: 2024
End Date: 2027
Funder: Marsden Fund
View Funded ActivityStart Date: 02-2020
End Date: 12-2024
Amount: $560,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 02-2018
End Date: 06-2021
Amount: $512,688.00
Funder: Australian Research Council
View Funded Activity