6 research outputs found
East African origins for Madagascan chickens as indicated by mitochondrial DNA
Published 22 March 2017The colonization of Madagascar by Austronesian-speaking people during AD 50–500 represents the most westerly point of the greatest diaspora in prehistory. A range of economically important plants and animals may have accompanied the Austronesians. Domestic chickens (Gallus gallus) are found in Madagascar, but it is unclear how they arrived there. Did they accompany the initial Austronesian-speaking populations that reached Madagascar via the Indian Ocean or were they late arrivals with Arabian and African sea-farers? To address this question, we investigated the mitochondrial DNA control region diversity of modern chickens sampled from around the Indian Ocean rim (Southeast Asia, South Asia, the Arabian Peninsula, East Africa and Madagascar). In contrast to the linguistic and human genetic evidence indicating dual African and Southeast Asian ancestry of the Malagasy people, we find that chickens in Madagascar only share a common ancestor with East Africa, which together are genetically closer to South Asian chickens than to those in Southeast Asia. This suggests that the earliest expansion of Austronesian-speaking people across the Indian Ocean did not successfully introduce chickens to Madagascar. Our results further demonstrate the complexity of the translocation history of introduced domesticates in Madagascar.Michael B. Herrera, Vicki A. Thomson, Jessica J.Wadley, Philip J. Piper, Sri Sulandari, Anik Budhi Dharmayanthi, Spiridoula Kraitsek, Jaime Gongora and Jeremy J. Austi
European and Asian contribution to the genetic diversity of mainland South American chickens
Chickens (Gallus gallus domesticus) from the Americas have long been recognized as descendants of European chickens, transported by early Europeans since the fifteenth century. However, in recent years, a possible pre-Columbian introduction of chickens to South America by Polynesian seafarers has also been suggested. Here, we characterize the mitochondrial control region genetic diversity of modern chicken populations from South America and compare this to a worldwide dataset in order to investigate the potential maternal genetic origin of modern-day chicken populations in South America. The genetic analysis of newly generated chicken mitochondrial control region sequences from South America showed that the majority of chickens from the continent belong to mitochondrial haplogroup E. The rest belongs to haplogroups A, B and C, albeit at very low levels. Haplogroup D, a ubiquitous mitochondrial lineage in Island Southeast Asia and on Pacific Islands is not observed in continental South America. Modern-day mainland South American chickens are, therefore, closely allied with European and Asian chickens. Furthermore, we find high levels of genetic contributions from South Asian chickens to those in Europe and South America. Our findings demonstrate that modern-day genetic diversity of mainland South American chickens appear to have clear European and Asian contributions, and less so from Island Southeast Asia and the Pacific Islands. Furthermore, there is also some indication that South Asia has more genetic contribution to European chickens than any other Asian chicken populations.Michael B. Herrera, Spiridoula Kraitsek, Jose A. Alcalde, Daniel Quiroz .... Vicki Thomson ... Jeremy J. Austin ... et al
Environmental variables, habitat discontinuity and life history shaping the genetic structure of Pomatoschistus marmoratus
Coastal lagoons are semi-isolated ecosystems
exposed to wide fluctuations of environmental conditions
and showing habitat fragmentation. These features may
play an important role in separating species into different
populations, even at small spatial scales. In this study, we
evaluate the concordance between mitochondrial (previous
published data) and nuclear data analyzing the genetic
variability of Pomatoschistus marmoratus in five localities,
inside and outside the Mar Menor coastal lagoon (SE
Spain) using eight microsatellites. High genetic diversity
and similar levels of allele richness were observed across
all loci and localities, although significant genic and
genotypic differentiation was found between populations
inside and outside the lagoon. In contrast to the FST values
obtained from previous mitochondrial DNA analyses
(control region), the microsatellite data exhibited significant
differentiation among samples inside the Mar Menor
and between lagoonal and marine samples. This pattern
was corroborated using Cavalli-Sforza genetic distances.
The habitat fragmentation inside the coastal lagoon and
among lagoon and marine localities could be acting as a
barrier to gene flow and contributing to the observed
genetic structure. Our results from generalized additive
models point a significant link between extreme lagoonal
environmental conditions (mainly maximum salinity) and
P. marmoratus genetic composition. Thereby, these environmental
features could be also acting on genetic structure
of coastal lagoon populations of P. marmoratus favoring
their genetic divergence. The mating strategy of P. marmoratus
could be also influencing our results obtained from
mitochondrial and nuclear DNA. Therefore, a special
consideration must be done in the selection of the DNA
markers depending on the reproductive strategy of the
species
Somatic mutations in salivary duct carcinoma and potential therapeutic targets
Background: Salivary duct carcinomas (SDCa) are rare highly aggressive malignancies. Most patients die from distant metastatic disease within three years of diagnosis. There are limited therapeutic options for disseminated disease. Results: 11 cases showed androgen receptor expression and 6 cases showed HER2 amplification. 6 Somatic mutations with additional available targeted therapies were identified: EGFR (p. G721A: Gefitinib), PDGFRA (p. H845Y: Imatinib and Crenolanib), PIK3CA (p. H1047R: Everolimus), ERBB2 (p. V842I: Lapatinib), HRAS (p. Q61R: Selumetinib) and KIT (p. T670I: Sorafenib). Furthermore, alterations in PTEN, PIK3CA and HRAS that alter response to androgen deprivation therapy and HER2 inhibition were also seen. Materials and Methods: Somatic mutation analysis was performed on DNA extracted from 15 archival cases of SDCa using the targeted Illumina TruSeq Amplicon Cancer Panel. Potential targetable genetic alterations were identified using extensive literature and international somatic mutation database (COSMIC, KEGG) search. Immunohistochemistry for androgen receptor and immunohistochemistry and fluorescent in situ hybridization for HER2 were also performed. Conclusions: SDCa show multiple somatic mutations, some that are amenable to pharmacologic manipulation and others that confer resistance to treatments currently under investigation. These findings emphasize the need to develop testing and treatment strategies for SDCa
Molecular patterns in salivary duct carcinoma identify prognostic subgroups
Salivary duct carcinoma (SDCa) is a rare cancer with high rate of metastases and poor survival despite aggressive multimodality treatment. This study analyzes the genetic changes in SDCa, their impact on cancer pathways, and evaluates whether molecular patterns can identify subgroups with distinct clinical characteristics and outcome. Clinicopathologic details and tissue samples from 66 patients (48 males, 18 females) treated between 1995 and 2018 were obtained from multiple institutions. Androgen receptor (AR) was assessed by immunohistochemistry, and the Illumina TruSight 170 gene panel was used for DNA sequencing. Male gender, lympho-vascular invasion, lymph node metastasis, and smoking were significant predictors of disease-free survival. AR was present in 79%. Frequently encountered alterations were mutations in TP53 (51%), PIK3CA (32%) and HRAS (22%), as well as amplifications of CDK4/6 (22%), ERBB2 (21%), MYC (16%), and deletions of CDKN2A (13%). TP53 mutation and MYC amplifications were associated with decreased disease-free survival. Analysis of cancer pathways revealed that the PI3K pathway was most commonly affected. Alterations in the cell cycle pathway were associated with impaired disease-free survival (HR 2.6, P = 0.038). Three subgroups based on AR and ERBB2 status were identified, which featured distinct molecular patterns and outcome. Among AR positive SDCa, HRAS mutations were restricted to AR positive tumors without ERBB2 amplification and HRAS mutations featured high co-occurrence with PIK3CA alterations, which seems specific to SDCa. AR negative SDCa were associated with poor disease-free survival in multivariate analysis (HR 4.5, P = 0.010) and none of these tumors exhibited ERBB2 amplification or HRAS mutations. AR and ERBB2 status in SDCa thus classifies tumors with distinct molecular profiles relevant to future targeted therapy. Furthermore, clinical factors such as smoking and molecular features such as MYC amplification may serve as markers of poor prognosis of SDCa