Physiological genomics in PG and beyond: July to September 2005

Mingyu Liang1 and Beverly Ventura2

1 Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; 2 Managing Editor, Physiological Genomics


    INTRODUCTION
 TOP
 INTRODUCTION
 COMPARATIVE GENOMICS
 COMPUTATIONAL MODELING OF...
 GENETICS OF OBESITY
 SKELETAL MUSCLE BIOLOGY
 CARDIOVASCULAR PHYSIOLOGICAL...
 DEVELOPMENTAL PHYSIOLOGICAL...
 CHARACTERIZATION OF INDIVIDUAL...
 TECHNICAL ADVANCES
 REFERENCES
 
BEGINNING WITH THIS ISSUE, Physiological Genomics (PG) will publish, on a quarterly basis, brief editorial perspectives entitled "Physiological genomics in PG and beyond." These articles will provide a brief, accessible summary of the studies published in PG in the most recent quarter, and relate those studies to aspects of physiological genomics that are being emphasized in PG and other leading journals.


    COMPARATIVE GENOMICS
 TOP
 INTRODUCTION
 COMPARATIVE GENOMICS
 COMPUTATIONAL MODELING OF...
 GENETICS OF OBESITY
 SKELETAL MUSCLE BIOLOGY
 CARDIOVASCULAR PHYSIOLOGICAL...
 DEVELOPMENTAL PHYSIOLOGICAL...
 CHARACTERIZATION OF INDIVIDUAL...
 TECHNICAL ADVANCES
 REFERENCES
 
PG has an ongoing Special Call for Papers in the area of Comparative Genomics. Studies in this area seek new biological and evolutionary insights by exploring and comparing the genome sequences recently made available in multiple species. Findings reported in this quarter of PG include the following.

  1. A comparison of up to 160 ion channel genes in Ciona with those in Caenorhabditis elegans, Drosophila, and vertebrates (78);
  2. Highly conserved genomic organization and tissue expression of bitter taste receptors in mouse and rat (120);
  3. Uncoupling protein 1 was expressed, but not induced, by cold exposures in fish (48);
  4. The expression pattern of the V-ATPase gene family in Drosophila (1); and
  5. The ß-defensin gene family formed syntenic clusters in human, chimpanzee, mouse, rat, and dog and was preferentially expressed in the male reproductive tract in rat (81).

Numerous studies, including a recent one by Geffeney et al. (37), have demonstrated the physiological significance of the evolutionary diversification of ion channel genes. The comparison between the Ciona and other genomes revealed selective loss and acquisition of ion channel genes during the evolution from invertebrates to vertebrates (78).

While the bitter taste receptors are largely conserved between mouse and rat (120), they have been shown by a recent study to undergo significant diversification in primates (80). The difference might be due to different levels of dietary evolution pressure in rodents and in primates. A comparison of these receptors between mouse and human (22) and a mapping of the taste neuronal circuitries (102) has also been published recently.

Uncoupling protein 1 (UCP1) mediates a nonshivering thermogenesis mechanism in brown adipose in mammals (60, 23) and could affect other tissues if expressed (55). The study by Jastroch et al. (48) showed the existence of UCP1 at an evolutionary time point several hundred million years earlier than previously thought. One of the first reports of the presence of a UCP homolog in birds was also published in PG (112).

V-ATPase genes encode ubiquitous proton pumps. In addition to regulating cellular acidification, a member of this gene family has been shown recently to also be important in synaptic vesicle fusion in Drosophila (44).

Defensins can be classified into {alpha}-, ß-, and {theta}-defensins. They are important antimicrobial peptides.


    COMPUTATIONAL MODELING OF PHYSIOLOGICAL SYSTEMS
 TOP
 INTRODUCTION
 COMPARATIVE GENOMICS
 COMPUTATIONAL MODELING OF...
 GENETICS OF OBESITY
 SKELETAL MUSCLE BIOLOGY
 CARDIOVASCULAR PHYSIOLOGICAL...
 DEVELOPMENTAL PHYSIOLOGICAL...
 CHARACTERIZATION OF INDIVIDUAL...
 TECHNICAL ADVANCES
 REFERENCES
 
An opinion piece by Beard et al. (3) and a related editorial by Allen Cowley, Jr., Editor-in-Chief of PG (24), were published this quarter to highlight the importance of computational modeling of physiological systems and PG’s interest in publishing studies in this area that apply computational approaches to link genome to complex physiology. The journal recently issued a Special Call for Papers on Computational Modeling (see http://www.the-aps.org/publications/specialcalls/pg.htm#compar).


    GENETICS OF OBESITY
 TOP
 INTRODUCTION
 COMPARATIVE GENOMICS
 COMPUTATIONAL MODELING OF...
 GENETICS OF OBESITY
 SKELETAL MUSCLE BIOLOGY
 CARDIOVASCULAR PHYSIOLOGICAL...
 DEVELOPMENTAL PHYSIOLOGICAL...
 CHARACTERIZATION OF INDIVIDUAL...
 TECHNICAL ADVANCES
 REFERENCES
 
A number of studies published this quarter in PG explored the genetics of obesity and related traits. Their findings include the following.

  1. A 15-cM region on chromosome 6 of a type 2 diabetic mouse model was associated with obesity (52);
  2. Four mouse quantitative trait loci (QTLs) that modify the effect of the Ser202Pro mutation in carboxypeptidase E on obesity and/or diabetes (20);
  3. Association of a polymorphism in UCP3 with body mass index in Caucasian families (71);
  4. Association of the polymorphisms of Kir6.2 and insulin variable number of tandem repeat (INS VNTR) with a trend toward lower insulin and higher glucose levels in young, obese Europeans (65); and
  5. A bioinformatics identification of hypothalamus-specific genes that might be of significance in obesity (6).

The approaches utilized by these studies ranged from QTL mapping and single nucleotide polymorphism (SNP) analysis to construction of congenic lines and gene expression profiling. As the necessary research tools continue to mature, the genetics and pathophysiology of obesity and related traits have become one of the significant themes of the studies recently published in PG (2, 28, 43, 50, 56, 70, 88, 97, 101, 114,) as well as other leading functional genomics journals (67, 68, 86, 107, 108, 123).

A number of review articles have summarized this recent progress in the study of obesity (4, 36, 75, 109).


    SKELETAL MUSCLE BIOLOGY
 TOP
 INTRODUCTION
 COMPARATIVE GENOMICS
 COMPUTATIONAL MODELING OF...
 GENETICS OF OBESITY
 SKELETAL MUSCLE BIOLOGY
 CARDIOVASCULAR PHYSIOLOGICAL...
 DEVELOPMENTAL PHYSIOLOGICAL...
 CHARACTERIZATION OF INDIVIDUAL...
 TECHNICAL ADVANCES
 REFERENCES
 
Molecular determinants of skeletal muscle performance are of significant interest because of the importance of muscle performance to the quality of life. What are addressed most frequently are the effects of exercise and aging on muscle performance and health. Recent issues of PG and other leading journals have included a number of studies that further our knowledge of these issues (5, 10, 19, 3840, 61, 69, 72, 77, 82, 89, 90, 93, 96, 98, 104, 106, 115).

This quarter saw characterization of gene expression profiles in human extraocular muscles (34), which extended what had been learned from related studies in the rat (8, 18, 35) and the mouse (87). The QTL analysis of the myostatin pathway (47) was an extension of a previous study from the same group (46).

Other findings in the area of skeletal muscle biology published this quarter in PG include the following.

  1. Knockout of sarcalumenin, a Ca2+-binding protein, in mice enhanced muscle resistance to fatigue (122);
  2. {alpha}-Sarcoglycan deficiency in mice caused increases in connective tissue and water contents in skeletal muscles without affecting their force (21);
  3. ATP-sensitive K+ channels in mice are essential to preventing running-induced muscle fiber damage (105);
  4. Gene expression profiles of rat skeletal muscles following denervation with or without electrical stimulation (59); and
  5. Four genes specifically upregulated in myotube-negative fast muscle of the tiger puffer fish (32).


    CARDIOVASCULAR PHYSIOLOGICAL GENOMICS
 TOP
 INTRODUCTION
 COMPARATIVE GENOMICS
 COMPUTATIONAL MODELING OF...
 GENETICS OF OBESITY
 SKELETAL MUSCLE BIOLOGY
 CARDIOVASCULAR PHYSIOLOGICAL...
 DEVELOPMENTAL PHYSIOLOGICAL...
 CHARACTERIZATION OF INDIVIDUAL...
 TECHNICAL ADVANCES
 REFERENCES
 
The heart remains one of the most popular organs for gene expression profiling studies. Examples of cardiac diseases or models that have been profiled by recent gene expression studies published in PG and other leading journals include human ischemic and nonischemic cardiomyopathy (54), rat compensated ventricular hypertrophy vs. heart failure (9, 58, 116), fibronectin-induced rat cardiac myocyte hypertrophy (15), mouse cardiac remodeling or heart failure (7, 76, 121), dogs fed a chronic high-fat diet (85), angiotensin II treatment (62), mouse cardiac allografts (74), blood from humans with cardiac allografts (45), aging in rats (27), human cardiac unloading with left ventricular assist device (17, 73), mouse with nitric oxide synthase-1 or -3 deficiency (12), mouse with aging and oxidative stress (30), diabetes in humans (113) and rats (57), and natural variations among Fundulus heteroclitus (79).

Gene expression profiles relevant to cardiovascular physiology and disease reported this quarter in PG include the following.

  1. Mouse atherosclerosis: a small set of genes was shown sufficient to classify the mouse disease and human coronary lesions with various degrees of severity or causes (103);
  2. Mouse heart after chronic constant or intermittent hypoxia (31);
  3. Aorta of spontaneously hypertensive rats with voluntary exercise: the aortic vessel distensibility was enhanced by exercise (42);
  4. Human coronary atherosclerosis (53);
  5. Kidneys from rats with acute hypotension: the aortic dilation capacity was diminished by acute hypotension (117); and
  6. Left ventricles of a rat model of intrinsic aerobic running capacity, correlated with a QTL analysis (63).

In another study, selective signaling pathways and calcineurin were examined in a mouse model of graded pressure stress (91).


    DEVELOPMENTAL PHYSIOLOGICAL GENOMICS
 TOP
 INTRODUCTION
 COMPARATIVE GENOMICS
 COMPUTATIONAL MODELING OF...
 GENETICS OF OBESITY
 SKELETAL MUSCLE BIOLOGY
 CARDIOVASCULAR PHYSIOLOGICAL...
 DEVELOPMENTAL PHYSIOLOGICAL...
 CHARACTERIZATION OF INDIVIDUAL...
 TECHNICAL ADVANCES
 REFERENCES
 
Gene expression profiles relevant to development were also reported this quarter in PG.

  1. Mouse metanephric mesenchyme at 24-h intervals from 10.5 days postcoitum to neonatal kidney, and in several anatomical regions (13); and
  2. Mouse embryonic day 8.5 (E8.5) yolk sac tissues deficient of Tek/Tie2, a receptor tyrosine kinase required for vasculature development (16).

Gene expression in the tips of the ureteric tree in mouse and rat (94) and mouse E10.5 metanephric mesenchyme (14) has been profiled recently in the literature, extending a number of earlier studies in this area (95, 99, 100).


    CHARACTERIZATION OF INDIVIDUAL GENES
 TOP
 INTRODUCTION
 COMPARATIVE GENOMICS
 COMPUTATIONAL MODELING OF...
 GENETICS OF OBESITY
 SKELETAL MUSCLE BIOLOGY
 CARDIOVASCULAR PHYSIOLOGICAL...
 DEVELOPMENTAL PHYSIOLOGICAL...
 CHARACTERIZATION OF INDIVIDUAL...
 TECHNICAL ADVANCES
 REFERENCES
 
Studies in PG this quarter also included characterization of two new genes.

  1. Mouse ancient conserved domain protein 2 was shown to be a widely expressed and regulated transporter for Mg2+ and other divalent cations in epithelial cells (41); and
  2. Frog atypical UCP4 was shown to be a potential evolutionary link between the Drosophila or C. elegans UCP4 and the mammalian UCP4 (51).


    TECHNICAL ADVANCES
 TOP
 INTRODUCTION
 COMPARATIVE GENOMICS
 COMPUTATIONAL MODELING OF...
 GENETICS OF OBESITY
 SKELETAL MUSCLE BIOLOGY
 CARDIOVASCULAR PHYSIOLOGICAL...
 DEVELOPMENTAL PHYSIOLOGICAL...
 CHARACTERIZATION OF INDIVIDUAL...
 TECHNICAL ADVANCES
 REFERENCES
 
PG’s Toolbox section is dedicated to publishing significant technological advances that recognize the importance of technology in furthering biomedical research. This quarter, PG published two Toolbox studies.

  1. Tracking interstitial cells of Cajal that generate intestinal pacemaking slow waves with a new green fluorescent protein knock-in mouse model (118); and
  2. Using individual samples appeared more robust than pooling samples in microarray analyses (49).

One of the strengths of a journal like PG is its capacity to include articles covering a broad range of species and special interests in the field. The remaining studies published this quarter in PG demonstrate this breadth of topics. They include the following.

  1. Characterization of the myogenic C2C12 cell line (26);
  2. A gene expression and phenotypic analysis of copper and iron metabolism in Saccharomyces cerevisiae (110);
  3. A gene expression and QTL analysis of bleomycin-induced pulmonary fibrosis (66);
  4. Nuclear architecture in the autosomal recessive mandibuloacral dysplasia (33); and
  5. Gene expression profiles in i) human bronchial epithelial cells exposed to interferon-{gamma} and/or dexamethasone (83); ii) horse wound margins (64); iii) rat traumatic spinal cord injury (25); iv) human peripheral mononuclear cells, suggesting the presence of marked individual variability (29); and v) human hepatocellular carcinoma cells exposed to hypoxia, cobalt, nickel, and deferoxamine (111).

Gene expression profiles in bronchial epithelial cells relevant to cystic fibrosis have been previously reported in PG (92, 119).

Autosomal recessive mandibuloacral dysplasia is caused by a mutation in lamin A/C. In addition to the deterioration of hereochromatin domains and nuclear envelope reported here (33), accumulation of lamin A precursor has recently been shown to sequester sterol regulatory element binding protein 1, which might contribute to the impairment of preadipocyte differentiation (11).


    FOOTNOTES
 
Article published online before print. See web site for date of publication (http://physiolgenomics.physiology.org).

Address for reprint requests and other correspondence: M. Liang, Dept. of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226 (e-mail: mliang{at}mcw.edu).

10.1152/physiolgenomics.00212.2005.


    REFERENCES
 TOP
 INTRODUCTION
 COMPARATIVE GENOMICS
 COMPUTATIONAL MODELING OF...
 GENETICS OF OBESITY
 SKELETAL MUSCLE BIOLOGY
 CARDIOVASCULAR PHYSIOLOGICAL...
 DEVELOPMENTAL PHYSIOLOGICAL...
 CHARACTERIZATION OF INDIVIDUAL...
 TECHNICAL ADVANCES
 REFERENCES
 

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  3. Beard DA, Bassingthwaighte JB, and Greene AS. Computational modeling of physiological systems. Physiol Genomics 23: 1–3, 2005.[Free Full Text]
  4. Bell CG, Walley AJ, and Froguel P. The genetics of human obesity. Nat Rev Genet 6: 221–234, 2005.[ISI][Medline]
  5. Bey L, Akunuri N, Zhao P, Hoffman EP, Hamilton DG, and Hamilton MT. Patterns of global gene expression in rat skeletal muscle during unloading and low-intensity ambulatory activity. Physiol Genomics 13: 157–167, 2003.[Abstract/Free Full Text]
  6. Bischof JM and Wevrick R. Genome-wide analysis of gene transcription in the hypothalamus. Physiol Genomics 22: 191–196, 2005.[Abstract/Free Full Text]
  7. Blaxall BC, Spang R, Rockman HA, and Koch WJ. Differential myocardial gene expression in the development and rescue of murine heart failure. Physiol Genomics 15: 105–114, 2003.[Abstract/Free Full Text]
  8. Budak MT, Bogdanovich S, Wiesen MH, Lozynska O, Khurana TS, and Rubinstein NA. Layer-specific differences of gene expression in extraocular muscles identified by laser-capture microscopy. Physiol Genomics 20: 55–65, 2004.[Abstract/Free Full Text]
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  15. Chen H, Huang XN, Stewart AF, and Sepulveda JL. Gene expression changes associated with fibronectin-induced cardiac myocyte hypertrophy. Physiol Genomics 18: 273–283, 2004.[Abstract/Free Full Text]
  16. Chen SH, Babichev Y, Rodrigues N, Voskas D, Ling L, Nguyen VPKH, and Dumont DJ. Gene expression analysis of Tek/Tie2 signaling. Physiol Genomics 22: 257–267, 2005.[Abstract/Free Full Text]
  17. Chen Y, Park S, Li Y, Missov E, Hou M, Han X, Hall JL, Miller LW, and Bache RJ. Alterations of gene expression in failing myocardium following left ventricular assist device support. Physiol Genomics 14: 251–260, 2003.[Abstract/Free Full Text]
  18. Cheng G, Merriam AP, Gong B, Leahy P, Khanna S, and Porter JD. Conserved and muscle-group-specific gene expression patterns shape postnatal development of the novel extraocular muscle phenotype. Physiol Genomics 18: 184–195, 2004.[Abstract/Free Full Text]
  19. Clarke DC, Miskovic D, Han XX, Calles-Escandon J, Glatz JF, Luiken JJ, Heikkila JJ, and Bonen A. Overexpression of membrane-associated fatty acid binding protein (FABPpm) in vivo increases fatty acid sarcolemmal transport and metabolism. Physiol Genomics 17: 31–37, 2004.[Abstract/Free Full Text]
  20. Collin GB, Maddatu TP, Sen S, and Naggert JK. Genetic modifiers interact with Cpefat to affect body weight, adiposity, and hyperglycemia. Physiol Genomics 22: 182–190, 2005.[Abstract/Free Full Text]
  21. Consolino CM, Duclos F, Lee J, Williamson RA, Campbell KP, and Brooks SV. Muscles of mice deficient in {alpha}-sarcoglycan maintain large masses and near control force values throughout the life span. Physiol Genomics 22: 244–256, 2005.[Abstract/Free Full Text]
  22. Conte C, Ebeling M, Marcuz A, Nef P, and Andres-Barquin PJ. Evolutionary relationships of the Tas2r receptor gene families in mouse and human. Physiol Genomics 14: 73–82, 2003.[Abstract/Free Full Text]
  23. Coulter AA, Bearden CM, Liu X, Koza RA, and Kozak LP. Dietary fat interacts with QTLs controlling induction of Pgc-1{alpha} and Ucp1 during conversion of white to brown fat. Physiol Genomics 14: 139–147, 2003.[Abstract/Free Full Text]
  24. Cowley AW Jr. Unifying conceptual frameworks of biological systems. Physiol Genomics 23: 4, 2005.[Free Full Text]
  25. De Biase A, Knoblach SM, Di Giovanni S, Fan C, Molon A, Hoffman EP, and Faden AI. Gene expression profiling of experimental traumatic spinal cord injury as a function of distance from impact site and injury severity. Physiol Genomics 22: 368–381, 2005.[Abstract/Free Full Text]
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  30. Edwards MG, Sarkar D, Klopp R, Morrow JD, Weindruch R, and Prolla TA. Age-related impairment of the transcriptional responses to oxidative stress in the mouse heart. Physiol Genomics 13: 119–127, 2003.[Abstract/Free Full Text]
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  39. Goetsch SC, Hawke TJ, Gallardo TD, Richardson JA, and Garry DJ. Transcriptional profiling and regulation of the extracellular matrix during muscle regeneration. Physiol Genomics 14: 261–271, 2003.[Abstract/Free Full Text]
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  42. Hagg U, Johansson ME, Gronros J, Naylor AS, Jonsdottir IH, Bergstrom G, Svensson PA, and Gan LM. Gene expression profile and aortic vessel distensibility in voluntarily exercised spontaneously hypertensive rats: potential role of heat shock proteins. Physiol Genomics 22: 319–326, 2005.[Abstract/Free Full Text]
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  52. Kim JH, Stewart TP, Zhang W, Kim HY, Nishina PM, and Naggert JK. Type 2 diabetes mouse model TallyHo carries an obesity gene on chromosome 6 that exaggerates dietary obesity. Physiol Genomics 22: 171–181, 2005.[Abstract/Free Full Text]
  53. King JY, Ferrara R, Tabibiazar R, Spin JM, Chen MM, Kuchinsky A, Vailaya A, Kincaid R, Tsalenko A, Deng DXF, Connolly A, Zhang P, Yang E, Watt C, Yakhini Z, Ben-Dor A, Adler A, Bruhn L, Tsao P, Quertermous T, and Ashley EA. Pathway analysis of coronary atherosclerosis. Physiol Genomics 23: 103–118, 2005.[Abstract/Free Full Text]
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  58. Kong SW, Bodyak N, Yue P, Liu Z, Brown J, Izumo S, and Kang PM. Genetic expression profiles during physiological and pathological cardiac hypertrophy and heart failure in rats. Physiol Genomics 21: 34–42, 2005.[Abstract/Free Full Text]
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