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Biomedical subjects

M Thomas P Gilbert

Publications and source records attributed to M Thomas P Gilbert.

At least 19 recordsLinked to original sources
PubMed2025

Persistent Genomic Erosion in Whooping Cranes Despite Demographic Recovery.

Integrating in-situ (wild) and ex-situ (captive) conservation efforts can mitigate genetic diversity loss and help prevent extinction of endangered wild populations. The whooping crane (Grus americana) experienced severe population declines in the 18th century, culminating in a collapse to ~20 individuals by 1944. Legal protections and conservation actions have since increased the census population from a stock of 16 individuals to approximately 840 individuals, yet the impact on genomic diversity remains unclear. We analysed the temporal dynamics of genomic erosion by sequencing a high-quality reference genome, and re-sequencing 16 historical (years 1867-1893) and 37 modern (2007-2020) genomes, including wild individuals and four generations of captive-bred individuals. Genomic demographic reconstructions reveal a steady decline, accelerating over the past 300 years with the European settlement of North America. Temporal genomic analyses show that despite demographic recovery, the species has lost 70% of its historical genetic diversity and has increased its inbreeding. Although the modern population bottleneck reduced the ancestral genetic load, modern populations possess more realised load than masked load, possibly resulting in a chronic loss of fitness. Integrating pedigree and genomic data, we underscore the role of breeding management in reducing recent inbreeding. Yet ongoing heterozygosity loss, load accumulation, and persistent effects of historical inbreeding (i.e., background inbreeding) argue against the species' downlisting from its current Endangered status on the IUCN Red List and the Endangered Species Act. The presence of private genetic variation in wild and captive populations suggests that wild-captive crosses could enhance genetic diversity and reduce the realised load. Our findings emphasise the role of genomics in informing conservation management and policy.

Animals↗
PubMed2025

Time-lagged genomic erosion and future environmental risks in a bird on the brink of extinction.

Global biodiversity is rapidly declining due to habitat degradation and genomic erosion, highlighting the urgent need to monitor endangered species and their genetic health. Temporal genomics and ecological modelling offer finer resolution than single-time-point measurements, providing a comprehensive view of species' recent and future trajectories. We investigated genomic erosion and environmental suitability in the critically endangered regent honeyeater (Anthochaera phrygia) by sequencing whole genomes of historical and modern specimens and building multi-temporal species distribution models (SDMs) across the last century. The species has declined from hundreds of thousands of individuals to fewer than 300 over the past 100 years. SDMs correctly predicted known patterns of local extinction in southeast Australia. Our demographic reconstructions revealed a gradual population decline from 2000 to 2500 years ago, sharply accelerating in the last 500 years due to climate variability and habitat loss. Despite this substantial demographic collapse, the regent honeyeater has lost only 9% of its genetic diversity, with no evidence of inbreeding or connectivity loss. Also, it exhibits higher diversity than many other threatened bird species. Forward-in-time genomic simulations indicate that this time lag between population decline and genetic diversity loss conceals the risk of ongoing genomic erosion into a future of rapidly degrading environmental suitability. Our work underscores the need for targeted conservation efforts and continuous genetic monitoring to prevent species extinction.

Animals↗
PubMed2007

A preliminary analysis of the DNA and diet of the extinct Beothuk: a systematic approach to ancient human DNA.

We have used a systematic protocol for extracting, quantitating, sexing and validating ancient human mitochondrial and nuclear DNA of one male and one female Beothuk, a Native American population from Newfoundland, which became extinct approximately 180 years ago. They carried mtDNA haplotypes, which fall within haplogroups X and C, consistent with Northeastern Native populations today. In addition we have sexed the male using a novel-sexing assay and confirmed the authenticity of his Y chromosome with the presence of the Native American specific Y-QM3 single nucleotide polymorphism (SNP). This is the first ancient nuclear SNP typed from a Native population in the Americas. In addition, using the same teeth we conducted a stable isotopes analysis of collagen and dentine to show that both individuals relied on marine sources (fresh and salt water fish, seals) with no hierarchy seen between them, and that their water sources were pooled or stored water. Both mtDNA sequence data and Y SNP data hint at possible gene flow or a common ancestral population for both the Beothuk and the current day Mikmaq, but more importantly the data do not lend credence to the proposed idea that the Beothuk (specifically, Nonosabasut) were of admixed (European-Native American) descent. We also analyzed patterns of DNA damage in the clones of authentic mtDNA sequences; there is no tendency for DNA damage to occur preferentially at previously defined mutational hotspots, suggesting that such mutational hotspots are not hypervariable because they are more prone to damage.

Base Sequence↗
PubMed2006

Evaluating Neanderthal genetics and phylogeny.

The retrieval of Neanderthal (Homo neanderthalsensis) mitochondrial DNA is thought to be among the most significant ancient DNA contributions to date, allowing conflicting hypotheses on modern human (Homo sapiens) evolution to be tested directly. Recently, however, both the authenticity of the Neanderthal sequences and their phylogenetic position outside contemporary human diversity have been questioned. Using Bayesian inference and the largest dataset to date, we find strong support for a monophyletic Neanderthal clade outside the diversity of contemporary humans, in agreement with the expectations of the Out-of-Africa replacement model of modern human origin. From average pairwise sequence differences, we obtain support for claims that the first published Neanderthal sequence may include errors due to postmortem damage in the template molecules for PCR. In contrast, we find that recent results implying that the Neanderthal sequences are products of PCR artifacts are not well supported, suffering from inadequate experimental design and a presumably high percentage (>68%) of chimeric sequences due to "jumping PCR" events.

Animals↗
PubMed2006

Recharacterization of ancient DNA miscoding lesions: insights in the era of sequencing-by-synthesis.

Although ancient DNA (aDNA) miscoding lesions have been studied since the earliest days of the field, their nature remains a source of debate. A variety of conflicting hypotheses exist about which miscoding lesions constitute true aDNA damage as opposed to PCR polymerase amplification error. Furthermore, considerable disagreement and speculation exists on which specific damage events underlie observed miscoding lesions. The root of the problem is that it has previously been difficult to assemble sufficient data to test the hypotheses, and near-impossible to accurately determine the specific strand of origin of observed damage events. With the advent of emulsion-based clonal amplification (emPCR) and the sequencing-by-synthesis technology this has changed. In this paper we demonstrate how data produced on the Roche GS20 genome sequencer can determine miscoding lesion strands of origin, and subsequently be interpreted to enable characterization of the aDNA damage behind the observed phenotypes. Through comparative analyses on 390,965 bp of modern chloroplast and 131,474 bp of ancient woolly mammoth GS20 sequence data we conclusively demonstrate that in this sample at least, a permafrost preserved specimen, Type 2 (cytosine-->thymine/guanine-->adenine) miscoding lesions represent the overwhelming majority of damage-derived miscoding lesions. Additionally, we show that an as yet unidentified guanine-->adenine analogue modification, not the conventionally argued cytosine-->uracil deamination, underpins a significant proportion of Type 2 damage. How widespread these implications are for aDNA will become apparent as future studies analyse data recovered from a wider range of substrates.

Animals↗
PubMed2006

Tracking down human contamination in ancient human teeth.

DNA contamination arising from the manipulation of ancient calcified tissue samples is a poorly understood, yet fundamental, problem that affects the reliability of ancient DNA (aDNA) studies. We have typed the mitochondrial DNA hypervariable region I of the only 6 people involved in the excavation, washing, and subsequent anthropological and genetic study of 23 Neolithic remains excavated from Granollers (Barcelona, Spain) and searched for their presence among the 572 clones generated during the aDNA analyses of teeth from these samples. Of the cloned sequences, 17.13% could be unambiguously identified as contaminants, with those derived from the people involved in the retrieval and washing of the remains present in higher frequencies than those of the anthropologist and genetic researchers. This finding confirms, for the first time, previous hypotheses that teeth samples are most susceptible to contamination at their initial excavation. More worrying, the cloned contaminant sequences exhibit substitutions that can be attributed to DNA damage after the contamination event, and we demonstrate that the level of such damage increases with time: contaminants that are >10 years old have approximately 5 times more damage than those that are recent. Furthermore, we demonstrate that in this data set, the damage rate of the old contaminant sequences is indistinguishable from that of the endogenous DNA sequences. As such, the commonly used argument that miscoding lesions observed among cloned aDNA sequences can be used to support data authenticity is misleading in scenarios where the presence of old contaminant sequences is possible. We argue therefore that the typing of those involved in the manipulation of the ancient human specimens is critical in order to ensure that generated results are accurate.

DNA, Mitochondrial↗
PubMed2005

Assessing the fidelity of ancient DNA sequences amplified from nuclear genes.

To date, the field of ancient DNA has relied almost exclusively on mitochondrial DNA (mtDNA) sequences. However, a number of recent studies have reported the successful recovery of ancient nuclear DNA (nuDNA) sequences, thereby allowing the characterization of genetic loci directly involved in phenotypic traits of extinct taxa. It is well documented that postmortem damage in ancient mtDNA can lead to the generation of artifactual sequences. However, as yet no one has thoroughly investigated the damage spectrum in ancient nuDNA. By comparing clone sequences from 23 fossil specimens, recovered from environments ranging from permafrost to desert, we demonstrate the presence of miscoding lesion damage in both the mtDNA and nuDNA, resulting in insertion of erroneous bases during amplification. Interestingly, no significant differences in the frequency of miscoding lesion damage are recorded between mtDNA and nuDNA despite great differences in cellular copy numbers. For both mtDNA and nuDNA, we find significant positive correlations between total sequence heterogeneity and the rates of type 1 transitions (adenine --> guanine and thymine --> cytosine) and type 2 transitions (cytosine --> thymine and guanine --> adenine), respectively. Type 2 transitions are by far the most dominant and increase relative to those of type 1 with damage load. The results suggest that the deamination of cytosine (and 5-methyl cytosine) to uracil (and thymine) is the main cause of miscoding lesions in both ancient mtDNA and nuDNA sequences. We argue that the problems presented by postmortem damage, as well as problems with contamination from exogenous sources of conserved nuclear genes, allelic variation, and the reliance on single nucleotide polymorphisms, call for great caution in studies relying on ancient nuDNA sequences.

Animals↗
PubMed2005

Assessing ancient DNA studies.

The study of ancient DNA has the potential to make significant and unique contributions to ecology and evolution. However, the techniques used contain inherent problems, particularly with regards to the generation of authentic and useful data. The solution currently advocated to reduce contamination and artefactual results is to adopt criteria for authentication. Nevertheless, these criteria are not foolproof, and we believe that they have, in practice, replaced the use of thought and prudence when designing and executing ancient DNA studies. We argue here that researchers in this field must take a more cognitive and self-critical approach. Specifically, in place of checking criteria off lists, researchers must explain, in sufficient enough detail to dispel doubt, how the data were obtained, and why they should be believed to be authentic.

Journal Article↗
PubMed2005

Resistance of degraded hair shafts to contaminant DNA.

We have investigated the susceptibility of degraded human hair shaft samples to contamination by exogenous sources of DNA, including blood, saliva, skin cells, and purified DNA. The results indicate that on the whole hair shafts are either largely resistant to penetration by contaminant DNA, or extremely easy to successfully decontaminate. This pertains to samples that are both morphologically and biochemically degraded. We suggest that this resistance to the incorporation of contaminant DNA relates to the hydrophobic and impermeable nature of the keratin structures forming the hair shaft. Therefore, hair samples represent an important and underestimated source of DNA in both forensic and ancient DNA studies.

Blood↗
PubMed2005

Critical review of host specificity and its coevolutionary implications in the fig/fig-wasp mutualism.

Figs (Ficus spp., Moraceae) and their pollinating wasps (Agaonidae, Chalcidoidea) constitute perhaps the most tightly integrated pollination mutualism that is known. Figs are characterized by extraordinarily high global and local species diversity. It has been proposed that the diversification of this mutualism has occurred through strict-sense coadaptation and cospeciation between pairs of fig and wasp species that are associated in highly specific one-to-one relationships. However, existing studies cast doubt on the generality of this proposition. Here, we review our current knowledge of the evolutionary history of the fig/fig-wasp mutualism. We critically examine the idea that codivergence between figs and their pollinators has been dominated by strict-sense cospeciation. We present phylogenetic and population genetic data from neotropical fig and fig wasp species that suggest that a more accurate model for diversification in this mutualism is that of groups of genetically well defined wasp species coevolving with genetically less well defined (frequently hybridizing) groups of figs. Last, we use our results to assess previously proposed hypotheses on models of speciation in this mutualism.

Animals↗
PubMed2005

mtDNA analysis of human remains from an early Danish Christian cemetery.

One of Denmark's earliest Christian cemeteries is Kongemarken, dating to around AD 1000-1250. A feature of early Scandinavian Christian cemeteries is sex segregation, with females buried on the northern sides and males on the southern sides. However, such separation was never complete; in the few early Christian cemeteries excavated in Scandinavia, there were always a few males placed on the north side, and some females on the south side. At Kongemarken, several males with juxtaposed females were found on the north side of the cemetery. Thus, to evaluate possible kinship relationships, and more general questions of population affinity, we analyzed mitochondrial DNA extracted from nine individuals excavated in two different areas within the cemetery: one male and four females from Area 1, and one male and three females from Area 2. Using stringent laboratory protocols, each individual was unequivocally assigned to a mitochondrial haplogroup. A surprising amount of haplogroup diversity was observed (Area 1: 1 U7 (male), 1 H, 1 I, 1 J, and 1 T2; Area 2: 2 H, 1 I, and 1 T, with one H being male); even the three subjects of haplogroup H were of different subtypes. This indicates that no subjects within each area were maternally related. The observed haplogroup, U7, while common in India and in western Siberian tribes, was not previously observed among present-day ethnic Scandinavians, and haplogroup I is rare (2%) in Scandinavia. These observations suggest that the individuals living in the Roskilde region 1,000 years ago were not all members of a tightly knit local population and comprised individuals with genetic links with populations that were from much farther away.

Age Determination by Skeleton↗
PubMed2005

Beringian paleoecology inferred from permafrost-preserved fungal DNA.

The diversity of fungi in permanently frozen soil from northeastern Siberia was studied by culture-independent PCR amplification of diverse environmental 18S rRNA genes. Elaborate protocols to avoid contamination during drilling, sampling, and amplification were used. A broad diversity of eukaryotic DNA sequences that were 510 bp long, including sequences of various fungi, plants, and invertebrates, could be obtained reproducibly from samples that were up to 300,000 to 400,000 years old. The sequences revealed that ancient fungal communities included a diversity of cold-adapted yeasts, dark-pigmented fungi, plant-parasitic fungi, and lichen mycobionts. DNA traces of tree-associated macrofungi in a modern tundra sample indicated that there was a shift in fungal diversity following the last ice age and supported recent results showing that there was a severe change in the plant composition in northeastern Siberia during this period. Interestingly, DNA sequences with high homology to sequences of coprophilic and keratinophilic fungi indicated that feces, hair, skin, and nails could have been sources of ancient megafauna DNA recently reported to be present in small amounts of Siberian permafrost sediments.

Cold Climate↗
PubMed2004

Rise and fall of the Beringian steppe bison.

The widespread extinctions of large mammals at the end of the Pleistocene epoch have often been attributed to the depredations of humans; here we present genetic evidence that questions this assumption. We used ancient DNA and Bayesian techniques to reconstruct a detailed genetic history of bison throughout the late Pleistocene and Holocene epochs. Our analyses depict a large diverse population living throughout Beringia until around 37,000 years before the present, when the population's genetic diversity began to decline dramatically. The timing of this decline correlates with environmental changes associated with the onset of the last glacial cycle, whereas archaeological evidence does not support the presence of large populations of humans in Eastern Beringia until more than 15,000 years later.

Alaska↗
PubMed2004

Most of the extant mtDNA boundaries in south and southwest Asia were likely shaped during the initial settlement of Eurasia by anatomically modern humans.

BACKGROUND: Recent advances in the understanding of the maternal and paternal heritage of south and southwest Asian populations have highlighted their role in the colonization of Eurasia by anatomically modern humans. Further understanding requires a deeper insight into the topology of the branches of the Indian mtDNA phylogenetic tree, which should be contextualized within the phylogeography of the neighboring regional mtDNA variation. Accordingly, we have analyzed mtDNA control and coding region variation in 796 Indian (including both tribal and caste populations from different parts of India) and 436 Iranian mtDNAs. The results were integrated and analyzed together with published data from South, Southeast Asia and West Eurasia. RESULTS: Four new Indian-specific haplogroup M sub-clades were defined. These, in combination with two previously described haplogroups, encompass approximately one third of the haplogroup M mtDNAs in India. Their phylogeography and spread among different linguistic phyla and social strata was investigated in detail. Furthermore, the analysis of the Iranian mtDNA pool revealed patterns of limited reciprocal gene flow between Iran and the Indian sub-continent and allowed the identification of different assemblies of shared mtDNA sub-clades. CONCLUSIONS: Since the initial peopling of South and West Asia by anatomically modern humans, when this region may well have provided the initial settlers who colonized much of the rest of Eurasia, the gene flow in and out of India of the maternally transmitted mtDNA has been surprisingly limited. Specifically, our analysis of the mtDNA haplogroups, which are shared between Indian and Iranian populations and exhibit coalescence ages corresponding to around the early Upper Paleolithic, indicates that they are present in India largely as Indian-specific sub-lineages. In contrast, other ancient Indian-specific variants of M and R are very rare outside the sub-continent.

Asia↗
PubMed2004

Absence of Yersinia pestis-specific DNA in human teeth from five European excavations of putative plague victims.

This study reports the results of a collaborative study undertaken by two independent research groups to (a) confirm recent PCR-based detection of Yersinia pestis DNA in human teeth from medieval plague victims in France, and (b) to extend these observations over five different European burial sites believed to contain plague victims dating from the late 13th to 17th centuries. Several different sets of primers were used, including those previously documented to yield positive results on ancient DNA extracts. No Y. pestis DNA could be amplified from DNA extracted from 108 teeth belonging to 61 individuals, despite the amplification of numerous other bacterial DNA sequences. Several methods of extracting dentine prior to the DNA extraction were also compared. PCR for bacterial 16S rDNA indicated the presence of multiple bacterial species in 23 out of 27 teeth DNA extracts where dentine was extracted using previously described methods. In comparison, positive results were obtained from only five out of 44 teeth DNA extracts for which a novel contamination-minimizing embedding technique was used. Therefore, high levels of environmental bacterial DNA are present in DNA extracts where previously described methods of tooth manipulation are used. To conclude, the absence of Y. pestis-specific DNA in an exhaustive search using specimens from multiple putative European plague burial sites does not allow us to confirm the identification of Y. pestis as the aetiological agent of the Black Death and subsequent plagues. In addition, the utility of the published tooth-based ancient DNA technique used to diagnose fatal bacteraemias in historical epidemics still awaits independent corroboration.

Base Sequence↗