18 research outputs found
A supermatrix analysis of genomic, morphological, and paleontological data from crown Cetacea
<p>Abstract</p> <p>Background</p> <p>Cetacea (dolphins, porpoises, and whales) is a clade of aquatic species that includes the most massive, deepest diving, and largest brained mammals. Understanding the temporal pattern of diversification in the group as well as the evolution of cetacean anatomy and behavior requires a robust and well-resolved phylogenetic hypothesis. Although a large body of molecular data has accumulated over the past 20 years, DNA sequences of cetaceans have not been directly integrated with the rich, cetacean fossil record to reconcile discrepancies among molecular and morphological characters.</p> <p>Results</p> <p>We combined new nuclear DNA sequences, including segments of six genes (~2800 basepairs) from the functionally extinct Yangtze River dolphin, with an expanded morphological matrix and published genomic data. Diverse analyses of these data resolved the relationships of 74 taxa that represent all extant families and 11 extinct families of Cetacea. The resulting supermatrix (61,155 characters) and its sub-partitions were analyzed using parsimony methods. Bayesian and maximum likelihood (ML) searches were conducted on the molecular partition, and a molecular scaffold obtained from these searches was used to constrain a parsimony search of the morphological partition. Based on analysis of the supermatrix and model-based analyses of the molecular partition, we found overwhelming support for 15 extant clades. When extinct taxa are included, we recovered trees that are significantly correlated with the fossil record. These trees were used to reconstruct the timing of cetacean diversification and the evolution of characters shared by "river dolphins," a non-monophyletic set of species according to all of our phylogenetic analyses.</p> <p>Conclusions</p> <p>The parsimony analysis of the supermatrix and the analysis of morphology constrained to fit the ML/Bayesian molecular tree yielded broadly congruent phylogenetic hypotheses. In trees from both analyses, all Oligocene taxa included in our study fell outside crown Mysticeti and crown Odontoceti, suggesting that these two clades radiated in the late Oligocene or later, contra some recent molecular clock studies. Our trees also imply that many character states shared by river dolphins evolved in their oceanic ancestors, contradicting the hypothesis that these characters are convergent adaptations to fluvial habitats.</p
The Phylogenetic Relationships and Biogeography of True Porpoises (Mammalia: Phocoenidae) Based On Morphological Data
Prior studies of phylogenetic relationships among phocoenids based on morphology and molecular sequence data conflict and yield unresolved relationships among species. This study evaluates a comprehensive set of cranial, postcranial, and soft anatomical characters to infer interrelationships among extant species and several well-known fossil phocoenids, using two different methods to analyze polymorphic data: polymorphic coding and frequency step matrix. Our phylogenetic results confirmed phocoenid monophyly. The division of Phocoenidae into two subfamilies previously proposed was rejected, as well as the alliance of the two extinct genera Salumiphocaena and Piscolithax with Phocoena dioptrica and Phocoenoides dalli. Extinct phocoenids are basal to all extant species. We also examined the origin and distribution of porpoises within the context of this phylogenetic framework. Phocoenid phylogeny together with available geologic evidence suggests that the early history of phocoenids was centered in the North Pacific during the middle Miocene, with subsequent dispersal into the southern hemisphere in the middle Pliocene. A cooling period in the Pleistocene allowed dispersal of the southern ancestor of Phocoena sinusinto the North Pacific (Gulf of California)
Fc-gamma receptor polymorphisms, cetuximab therapy, and overall survival in the CCTG CO.20 trial of metastatic colorectal cancer
Background
Two germ line Fc-γ receptor (FCGR) polymorphisms, rs1801274 [FCGR2A; His(H)131Arg(R)] and rs396991 [FCGR3A; Phe(F)158Val(V)], produce altered proteins through amino acid substitutions. We previously reported that the FCGR2A H/H genotype was associated with longer overall survival (OS) in cetuximab-treated chemotherapy-refractory patients with metastatic colorectal cancer. Here, we aimed to replicate and extend this finding in the Canadian Clinical Trials Group CO.20 trial.
Methods
After germ line DNA genotyping, polymorphic relationships with survival were assessed using log-rank tests and hazard ratios (HR) from Cox proportional hazard models, adjusting for known prognostic factors. The dominant genetic inheritance model was used for the main analysis.
Results
Of 592 wild-type KRAS patients treated with cetuximab, those with the FCGR2A H/H genotype (n = 165, 28%) had improved OS (HR: 0.66, P < 0.001; median absolute benefit, 1.3 months) compared to those with R/- genotype (n = 427, 72%). Patients with H/R had intermediate results under a codominant genetic inheritance model (HR: 0.72, P = 0.003). No significant associations were found between FCGR3A genotype and OS. In an exploratory analysis, patients with the combination of FCGR2A H/H + FCGR3A F/F genotype had significantly better OS (HR: 0.33, P = 0.003; median absolute benefit, 12.5 months) than patients with the combination of double-variant R/R + V/V genotype. Progression-free survival results were similar to OS. Toxicity rates were not associated with either polymorphism.
Conclusions
The FCGR2A genotype was associated with efficacy but not with toxicity in wild-type KRAS, cetuximab-treated colorectal cancer patients. FCGR3A genotype may modulate the relationship between FCGR2A polymorphism and outcome. FCGR2A is a promising biomarker for clinical management for these patients
Fc-gamma receptor polymorphisms, cetuximab therapy, and overall survival in the CCTG CO.20 trial of metastatic colorectal cancer
Mitochondrial genomics reveals the evolutionary history of the porpoises (Phocoenidae) across the speciation continuum.
International audienceHistorical variation in food resources is expected to be a major driver of cetacean evolution, especially for the smallest species like porpoises. Despite major conservation issues among porpoise species (e.g., vaquita and finless), their evolutionary history remains understudied. Here, we reconstructed their evolutionary history across the speciation continuum. Phylogenetic analyses of 63 mitochondrial genomes suggest that porpoises radiated during the deep environmental changes of the Pliocene. However, all intra-specific subdivisions were shaped during the Quaternary glaciations. We observed analogous evolutionary patterns in both hemispheres associated with convergent evolution to coastal versus oceanic environments. This suggests that similar mechanisms are driving species diversification in northern (harbor and Dall's) and southern species (spectacled and Burmeister's). In contrast to previous studies, spectacled and Burmeister's porpoises shared a more recent common ancestor than with the vaquita that diverged from southern species during the Pliocene. The low genetic diversity observed in the vaquita carried signatures of a very low population size since the last 5,000 years. Cryptic lineages within Dall's, spectacled and Pacific harbor porpoises suggest a richer evolutionary history than previously suspected. These results provide a new perspective on the mechanisms driving diversification in porpoises and an evolutionary framework for their conservation