How the enormous structural and functional diversity of new genes and proteins was generated (estimated to be 10^10-10^12 different proteins in all organisms on earth [Choi I-G, Kim S-H. 2006. Evolution of protein structural classes and protein sequence families. Proc Natl Acad Sci 103: 14056â14061] is a central biological question that has a long and rich history. Extensive work during the last 80 years have shown that new genes that play important roles in lineage-specific phenotypes and adaptation can originate through a multitude of different mechanisms, including duplication, lateral gene transfer, gene fusion/fission, and de novo origination. In this review, we focus on two main processes as generators of new functions: evolution of new genes by duplication and divergence of pre-existing genes and de novo gene origination in which a whole protein-coding gene evolves from a noncoding sequence.
Sisters and brothers are completely unrelated with respect to the sex chromosomes they inherit from their heterogametic parent. This has the potential to result in a previously unappreciated form of genetic conflict between the sex chromosomes, called sexually antagonistic zygotic drive (SA-ZD). SA-ZD can arise whenever brothers and sisters compete over limited resources or there is brother-sister mating coupled with inbreeding depression. Although theory predicts that SA-ZD should be common and influence important evolutionary processes, there is little empirical evidence for its existence. Here we discuss the current understanding of SA-ZD, why it would be expected to elude empirical detection when present, and how it relates to other forms of genetic conflict.
The origin of the eukaryotic cell can be regarded as one of the hallmarks in the history of life on our planet. The apparent genomic chimerism in eukaryotic genomes is currently best explained by invoking a cellular fusion at the root of the eukaryotes that involves one archaeal and one or more bacterial components. Here, we use a phylogenomics approach to reevaluate the evolutionary affiliation between Archaea and eukaryotes, and provide further support for scenarios in which the nuclear lineage in eukaryotes emerged from within the archaeal radiation, displaying a strong phylogenetic affiliation with, or even within, the archaeal TACK superphylum. Further taxonomic sampling of archaeal genomes in this superphylum will certainly provide a better resolution in the events that have been instrumental for the emergence of the eukaryotic lineage.
The receptors for platelet-derived growth factor (PDGF) and stem cell factor (SCF) are members of the type III class of PTK receptors, which are characterized by five Ig-like domains extracellularly and a split kinase domain intracellularly. The receptors are activated by ligand-induced dimerization, leading to autophosphorylation on specific tyrosine residues. Thereby the kinase activities of the receptors are activated and docking sites for downstream SH2 domain signal transduction molecules are created; activation of these pathways promotes cell growth, survival, and migration. These receptors mediate important signals during the embryonal development, and control tissue homeostasis in the adult. Their overactivity is seen in malignancies and other diseases involving excessive cell proliferation, such as atherosclerosis and fibrotic diseases. In cancer, mutations of PDGF and SCF receptors-including gene fusions, point mutations, and amplifications-drive subpopulations of certain malignancies, such as gastrointestinal stromal tumors, chronic myelomonocytic leukemia, hypereosinophilic syndrome, glioblastoma, acute myeloid leukemia, mastocytosis, and melanoma.
Communication between cells in a multicellular organism occurs by the production of ligands (proteins, peptides, fatty acids, steroids, gases, and other low-molecular-weight compounds) that are either secreted by cells or presented on their surface, and act on receptors on, or in, other target cells. Such signals control cell growth, migration, survival, and differentiation. Signaling receptors can be single-span plasma membrane receptors associated with tyrosine or serine/threonine kinase activities, proteins with seven transmembrane domains, or intracellular receptors. Ligand-activated receptors convey signals into the cell by activating signaling pathways that ultimately affect cytosolic machineries or nuclear transcriptional programs or by directly translocating to the nucleus to regulate transcription.
Transforming growth factor beta (TGF-beta) family members signal via heterotetrameric complexes of type I and type II dual specificity kinase receptors. The activation and stability of the receptors are controlled by posttranslational modifications, such as phosphorylation, ubiquitylation, sumoylation, and neddylation, as well as by interaction with other proteins at the cell surface and in the cytoplasm. Activation of TGF-beta receptors induces signaling via formation of Smad complexes that are translocated to the nucleus where they act as transcription factors, as well as via non-Smad pathways, including the Erk1/2, JNK and p38 MAP kinase pathways, and the Src tyrosine kinase, phosphatidylinositol 30-kinase, and Rho GTPases.
Epithelia exist in the animal body since the onset of embryonic development; they generate tissue barriers and specify organs and glands. Through epithelial-mesenchymal transitions (EMTs), epithelia generate mesenchymal cells that form new tissues and promote healing or disease manifestation when epithelial homeostasis is challenged physiologically or pathologically. Transforming growth factor-beta s (TGF-beta s), activins, bone morphogenetic proteins (BMPs), and growth and differentiation factors (GDFs) have been implicated in the regulation of epithelial differentiation. These TGF-beta family ligands are expressed and secreted at sites where the epithelium interacts with the mesenchyme and provide paracrine queues from the mesenchyme to the neighboring epithelium, helping the specification of differentiated epithelial cell types within an organ. TGF-beta ligands signal via Smads and cooperating kinase pathways and control the expression or activities of key transcription factors that promote either epithelial differentiation or mesenchymal transitions. In this review, we discuss evidence that illustrates how TGF-beta family ligands contribute to epithelial differentiation and induce mesenchymal transitions, by focusing on the embryonic ectoderm and tissues that form the external mammalian body lining.
Epithelial cells contribute to the development of various vital organs by generating tubular and/or glandular architectures. The fully developed forms of ductal organs depend on processes of branching morphogenesis, whereby frequency, total number, and complexity of the branching tissue define the final architecture in the organ. Some ductal tissues, like the mammary gland during pregnancy and lactation, disintegrate and regenerate through periodic cycles. Differentiation of branched epithelia is driven by antagonistic actions of parallel growth factor systems that mediate epithelial-mesenchymal communication. Transforming growth factor-beta (TGF-beta) family members and their extracellular antagonists are prominently involved in both normal and disease-associated (e.g., malignant or fibrotic) ductal tissue patterning. Here, we discuss collective knowledge that permeates the roles of TGF-beta family members in the control of the ductal tissues in the vertebrate body.
Endothelial cell - cell adherens junctions (AJs) supervise fundamental vascular functions, such as the control of permeability and transmigration of circulating leukocytes, and the maintenance of existing vessels and formation of new ones. These processes are often dysregulated in pathologies. However, the evidence that links dysfunction of endothelial AJs to human pathologies is mostly correlative. In this review, we present an update of the molecular organization of AJ complexes in endothelial cells (ECs) that is mainly based on observations from experimental models. Furthermore, we report in detail on a human pathology, cerebral cavernous malformation (CCM), which is initiated by loss-of-function mutations in the genes that encode the three cytoplasmic components of AJs (CCM1, CCM2, and CCM3). At present, these represent a unique example of mutations in components of endothelial AJs that cause human disease. We describe also how studies into the defects of AJs in CCM are shedding light on the crucial regulatory mechanisms and signaling activities of these endothelial structures. Although these observations are specific for CCM, they support the concept that dysfunction of endothelial AJs can directly contribute to human pathologies.
The transforming growth factor-beta (TGF-beta) is the prototype of the TGF-beta family of growth and differentiation factors, which is encoded by 33 genes in mammals and comprises homo- and heterodimers. This review introduces the reader to the TGF-beta family with its complexity of names and biological activities. It also introduces TGF-beta as the best-studied factor among the TGF-beta family proteins, with its diversity of roles in the control of cell proliferation and differentiation, wound healing and immune system, and its key roles in pathology, for example, skeletal diseases, fibrosis, and cancer.
Anthropogenic impacts on the environment alter speciation processes by affecting both geographical contexts and selection patterns on a worldwide scale. Here we review evidence of these effects. We find that human activities often generate spatial isolation between populations and thereby promote genetic divergence but also frequently cause sudden secondary contact and hybridization between diverging lineages. Human-caused environmental changes produce new ecological niches, altering selection in diverse ways that can drive diversification; but changes also often remove niches and cause extirpations. Human impacts that alter selection regimes are widespread and strong in magnitude, ranging from local changes in biotic and abiotic conditions to direct harvesting to global climate change. Altered selection, and evolutionary responses to it, impacts early-stage divergence of lineages, but does not necessarily lead toward speciation and persistence of separate species. Altogether, humans both promote and hinder speciation, although new species would form very slowly relative to anthropogenic hybridization, which can be nearly instantaneous. Speculating about the future of speciation, we highlight two key conclusions: (1) Humans will have a large influence on extinction and "despeciation" dynamics in the short term and on early-stage lineage divergence, and thus potentially speciation in the longer term, and (2) long-term monitoring combined with easily dated anthropogenic changes will improve our understanding of the processes of speciation. We can use this knowledge to preserve and restore ecosystems in ways that promote (re-)diversification, increasing future opportunities of speciation and enhancing biodiversity.