Explore the vast range of titles available.

This illustrated book describes how some finned vertebrates acquired limbs, giving rise to more than 25,000 extant terrapod species. Michel Laurin uses paleontological, geological, physiological, and comparative anatomical data to describe this monumental event. Along with discussing the evolutionary pressures that may have led vertebrates onto dry land, the author also shows how extant vertebrates yield clues about the conquest of land and how scientists uncover evolutionary history.--[book cover]

More than three hundred million years ago—a relatively recent date in the two billion years since life first appeared—vertebrate animals first ventured onto land. This usefully illustrated book describes how some finned vertebrates acquired limbs, giving rise to more than 25,000 extant tetrapod species. Michel Laurin uses paleontological, geological, physiological, and comparative anatomical data to describe this monumental event. He summarizes key concepts of modern paleontological research, including biological nomenclature, paleontological and molecular dating, and the methods used to infer phylogeny and character evolution. Along with a discussion of the evolutionary pressures that may have led vertebrates onto dry land, the book also shows how extant vertebrates yield clues about the conquest of land and how scientists uncover evolutionary history.

Amphibian pulmonary and systemic vascular circuits are arranged in parallel, with potentially important consequences for resistance ( R ) to blood flow. The contribution of the parallel anatomic arrangement to total vascular R ( R T ), independent of blood viscosity, is unknown. We measured pulmonary ( R P ) and systemic ( R S ) vascular R with an in situ Ringer’s solution perfusion technique using anesthetized anuran and urodele species to determine: (1) relative contributions of vascular anatomy and blood viscosity to R T ; (2) distensibility index (%Δ flow kPa −1 ) of the pulmonary and systemic vascular circuits; and (3) interspecific correlates of variation in these parameters with red blood cell size, cardiac power output, and aerobic capacities. R P was lower than R S in anurans, while R P of the urodeles was greater than R S and significantly greater than anuran R P . Anuran R T was lowest and did not vary interspecifically, whereas urodele R T was significantly greater than anuran, and varied interspecifically. Pulmonary and systemic circuit distensibility differences may explain cardiac shunt patterns in toads with changes in cardiac output from rest to activity. When blood viscosity was taken into account, vascular resistance accounted for about 25 % of R T while blood viscosity accounted for the remaining 75 %. Owing to lower R T , terrestrial anuran species required lower cardiac power outputs when moving fluid through their vasculature compared to aquatic species. These results indicate that physical characteristics of the vasculature can account for interspecific differences in cardiovascular physiology and suggest a co-evolution of cardiac and vascular anatomy among amphibians.

An analysis of 16 health-related quantitative traits in approximately 350,000 individuals reveals statistically significant associations between genome-wide homozygosity and four complex traits (height, lung function, cognitive ability and educational attainment); in each case increased homozygosity associates with a decreased trait value, but no evidence was seen of an influence on blood pressure, cholesterol, or ten other cardio-metabolic traits. Parental relatedness link to height and intelligence This consortium meta-analysis of 102 cohorts and more than 350,000 individuals investigates the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity, ROH), which are inferred to be homozygous along their complete length. Focusing on 16 health-related quantitative traits, the authors find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in a second, general cognitive ability and educational attainment. In each case increased homozygosity associates with decreased trait value. No evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Homozygosity has long been associated with rare, often devastating, Mendelian disorders 1 , and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness 2 . However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power 3 , 4 . Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment ( P < 1 × 10 −300 , 2.1 × 10 −6 , 2.5 × 10 −10 and 1.8 × 10 −10 , respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months’ less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples 5 , 6 , no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection 7 , this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

In patients with impaired lung function who are scheduled for lung surgery, a means of estimating the ventilatory consequences of parenchymal resection is needed. We have tested the ability of lung scanning with aerosolized and intravenous 133Xe to fulfil this purpose in 100 pneumonectomized or lobectomized patients. Postsurgery VC and FEV1 values were evaluated as follows: each lung was horizontally divided into two areas and lower and upper VC values were calculated as percentages of the total radioactivity count. Using the regional percentages and the absolute values of VC measured spirometrically, the VC expected postsurgery values were calculated according to the type of resection planned (e. g. if the left lung was to be removed and if it accounted for 50% of the radioactivity on the scan, the postsurgery VC would be halved). Postsurgery FEV1 values were estimated by using the VC value and the FEV1/VC ratio measured before surgery. A significant correlation (p < 0.001) was found between the values estimated in such way and the actual FEV1 and VC values obtained shortly after surgery (between 6 and 15 days). From these results, we conclude that the xenon scan is a valuable technique for estimating the consequences of lung removal on ventilation.

This chapter takes the dogma of development and shows how it becomes part of the continuum of evolution using the provided principles. Calcium homeostasis counterbalanced by lipid homeostasis seems to underlie all of cellular evolution. All of the features of parathyroid hormone‐related protein (PTHrP) biology justify its use as an archetype for the proposed model of lung evolution. One of the predictions of the cellular‐molecular integrated approach to evolution is the primacy of the unicellular state as the founding and ongoing mechanism of evolution. By using the cellular‐molecular ontogenetic and phylogenetic approach described in the chapter for the water‐land transition as a major impetus for evolution, a similar approach can be used moving both forward and backward developmentally and phylogenetically from that critically important phase of vertebrate evolution. This approach will yield a priori knowledge about the first principles of physiology, and how they have evolved to generate form and function from their unicellular origins.

This chapter describes the utility of understanding the nature of neutral lipid trafficking in the lung alveolus and its evolutionary exploitation for broadening the knowledge of other vertebrate physiologic traits. The discovery that neutral lipid trafficking mediates the well‐recognized on‐demand property of lung surfactant production has provided important insights to the specific mechanisms that regulate lung alveolar development, homeostasis, and repair. The identification of adipocyte differentiation related protein (ADRP) as the physiologic entity responsible for neutral lipid trafficking provides a portal to deep vertebrate homologies relevant to ancient mechanisms of lipid metabolism as early in phylogeny as fungi. The chapter describes how the perilipin‐ADRP‐TIP47 (PAT) proteins regulate cellular lipid metabolism in both mammals and model organisms. The PAT family of lipid droplet proteins is comprised of five members in mammals: perilipin; ADRP; tail‐interacting protein of 47 kilodaltons (TIP47); S3‐12; and OXPAT.

Lung cancer is the leading cause of cancer-associated mortality worldwide 1 . Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS . We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET , ROS1 , ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource. Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

There has been a dramatic increase in the detection of lung nodules, many of which are preneoplasia atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) or invasive adenocarcinoma (ADC). The molecular landscape and the evolutionary trajectory of lung preneoplasia have not been well defined. Here, we perform multi-region exome sequencing of 116 resected lung nodules including AAH (n = 22), AIS (n = 27), MIA (n = 54) and synchronous ADC (n = 13). Comparing AAH to AIS, MIA and ADC, we observe progressive genomic evolution at the single nucleotide level and demarcated evolution at the chromosomal level supporting the early lung carcinogenesis model from AAH to AIS, MIA and ADC. Subclonal analyses reveal a higher proportion of clonal mutations in AIS/MIA/ADC than AAH suggesting neoplastic transformation of lung preneoplasia is predominantly associated with a selective sweep of unfit subclones. Analysis of multifocal pulmonary nodules from the same patients reveal evidence of convergent evolution. There has been a drastic increase in detection of lung nodules, many of which are precancers, preinvasive, minimally invasive or sometimes invasive lung cancers. Here, Hu et al. perform multi-region exome sequencing to discern the evolutional trajectory from precancers to invasive lung cancers.

The evolutionary processes that underlie the marked sensitivity of small cell lung cancer (SCLC) to chemotherapy and rapid relapse are unknown 1 – 3 . Here we determined tumour phylogenies at diagnosis and throughout chemotherapy and immunotherapy by multiregion sequencing of 160 tumours from 65 patients. Treatment-naive SCLC exhibited clonal homogeneity at distinct tumour sites, whereas first-line platinum-based chemotherapy led to a burst in genomic intratumour heterogeneity and spatial clonal diversity. We observed branched evolution and a shift to ancestral clones underlying tumour relapse. Effective radio- or immunotherapy induced a re-expansion of founder clones with acquired genomic damage from first-line chemotherapy. Whereas TP53 and RB1 alterations were exclusively part of the common ancestor, MYC family amplifications were frequently not constituents of the founder clone. At relapse, emerging subclonal mutations affected key genes associated with SCLC biology, and tumours harbouring clonal CREBBP / EP300 alterations underwent genome duplications. Gene-damaging TP53 alterations and co-alterations of TP53 missense mutations with TP73 , CREBBP / EP300 or FMN2 were significantly associated with shorter disease relapse following chemotherapy. In summary, we uncover key processes of the genomic evolution of SCLC under therapy, identify the common ancestor as the source of clonal diversity at relapse and show central genomic patterns associated with sensitivity and resistance to chemotherapy. We uncover key processes of the genomic evolution of small cell lung cancer under therapy, identify the common ancestor as the source of clonal diversity at relapse and show central genomic patterns associated with drug response.