Journal of Genetics and Genomics

Global view of bionetwork dynamics: adaptive landscape

Ping Ao

2009, 36(2): 63-73. doi: 10.1016/S1673-8527(08)60093-4

Abstract (81) HTML PDF (3)

Abstract:
Based on recent work, I will give a nontechnical brief review of a powerful quantitative concept in biology, adaptive landscape, initially proposed by S. Wright over 70 years ago, reintroduced by one of the founders of molecular biology and by others in different biological contexts, but apparently forgotten by modern biologists for many years. Nevertheless, this concept finds an increasingly important role in the development of systems biology and bionetwork dynamics modeling, from phage lambda genetic switch to endogenous network for cancer genesis and progression. It is an ideal quantification to describe the robustness and stability of bionetworks. Here, I will first introduce five landmark proposals in biology on this concept, to demonstrate an important common thread in theoretical biology. Then I will discuss a few recent results, focusing on the studies showing theoretical consistency of adaptive landscape. From the perspective of a working scientist and of what is needed logically for a dynamical theory when confronting empirical data, the adaptive landscape is useful both metaphorically and quantitatively, and has captured an essential aspect of biological dynamical processes. Though at the theoretical level the adaptive landscape must exist and it can be used across hierarchical boundaries in biology, many associated issues are indeed vague in their initial formulations and their quantitative realizations are not easy, and are good research topics for quantitative biologists. I will discuss three types of open problems associated with the adaptive landscape in a broader perspective.

Histone modifications dictate specific biological readouts

Anjana Munshi, Gowhar Shafi, Nishat Aliya, Akka Jyothy

2009, 36(2): 75-88. doi: 10.1016/S1673-8527(08)60094-6

Abstract (65) HTML PDF (1)

Abstract:
The basic unit of chromatin is the nucleosomal core particle, containing 147 bp of DNA that wraps twice around an octamer of core histones. The core histones bear a highly dynamic N-terminal amino acid tail around 20–35 residues in length and rich in basic amino acids. These tails extending from the surface of nucleosome play an important role in folding of nucleosomal arrays into higher order chromatin structure, which plays an important role in eukaryotic gene regulation. The amino terminal tails protruding from the nuclesomes get modified by the addition of small groups such as methyl, acetyl and phosphoryl groups. In this review, we focus on these complex modification patterns and their biological functions. Moreover, these modifications seem to be part of a complex scheme where distinct histone modifications act in a sequential manner or in combination to form a “histone code” read by other proteins to control the structure and/or function of the chromatin fiber. Errors in this histone code may be involved in many human diseases especially cancer, the nature of which could be therapeutically exploited. Increasing evidence suggests that many proteins bear multiple, distinct modifications, and the ability of one modification to antagonize or synergize the deposition of another can have significant biological consequences.

Bivariate whole-genome linkage scan for bone geometry and total body fat mass

Shufeng Lei, Feiyan Deng, Peng Xiao, Kai Zhong, Hongyi Deng, Robert R. Recker, Hongwen Deng

2009, 36(2): 89-97. doi: 10.1016/S1673-8527(08)60095-8

Abstract (49) HTML PDF (0)

Abstract:
To quantify the genetic correlations between total body fat mass (TBFM) and femoral neck geometric parameters (FNGPs) and, if possible, to detect the specific genomic regions shared by them, bivariate genetic analysis and bivariate whole-genome linkage scan were carried out in a large Caucasian population. All the phenotypes studied were significantly controlled by genetic factors (P < 0.001) with the heritabilities ranging from 0.45 to 0.68. Significantly genetic correlations were found between TBFM and CSA (cross-section area), W (sub-periosteal diameter), Z (section modulus) and CT (cortical thickness) except between TBFM and BR (buckling ratio). The peak bivariate LOD scores were 3.23 (20q12), 2.47 (20p11), 3.19 (6q27), 1.68 (20p12), and 2.47 (7q11) for the five pairs of TBFM and BR, CSA, CT, W, and Z in the entire sample, respectively. Gender-specific bivariate linkage evidences were also found for the five pairs. 6p25 had complete pleiotropic effects on the variations of TBFM & Z in the female sub-population, and 6q27 and 17q11 had coincident linkages for TBFM & CSA and TBFM & Z in the entire population. We identified moderate genetic correlations and several shared genomic regions between TBFM and FNGPs in a large Caucasian population.

Characterization of Arabidopsis MYB transcription factor gene AtMYB17 and its possible regulation by LEAFY and AGL15

Yunfei Zhang, Guangyu Cao, Li-Jia Qu, Hongya Gu

2009, 36(2): 99-107. doi: 10.1016/S1673-8527(08)60096-X

Abstract (113) HTML PDF (2)

Abstract:
MYB transcription factors compose one of the largest transcription factor families in Arabidopsis, which play important roles in various developmental processes as well as defense responses against environmental stresses. In this study, we report the characterization of AtMYB17 gene, a putative R2R3 type MYB gene family member in Arabidopsis. AtMYB17 was found exclusively localized in nuclear, with an activation domain at its C-terminus. AtMYB17 was highly expressed in inflorescences and siliques, especially at early flower developmental stages. The level of AtMYB17 transcripts was also found to increase after imbibition during seed germination and gradually concentrate to the shoot apex. Bioinformatics analysis identified several binding sites of LEAFY (LFY) and AGL15 in the promoter region of AtMYB17. Promoter-GUS fusion analysis showed that the LFY binding sites were important in fine-tuning regulation of the spatio-temporal expression of AtMYB17 in transgenic plants. Moreover, AtMYB17 was up-regulated in 35S::AGL15 plants. Taken together, our data suggest that LFY may be involved in the regulation of AtMYB17, possibly together with AGL15, and thereafter in early inflorescence development and seed germination.

Cloning of the kininogen gene from Lampetra japonica provides insights into its phylogeny in vertebrates

Liwei Zhou, Xin Liu, Ping Jin, Qingwei Li

2009, 36(2): 109-115. doi: 10.1016/S1673-8527(08)60097-1

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Abstract:
Kininogens, the precursors of bradykinins, ubiquitously exist in vertebrates, including mammals, birds, amphibians, and fishes. To elucidate the phylogeny of kininogen genes in early vertebrates, we cloned the full-length cDNA of kininogen gene from the liver of Lampetra japonica. The open reading frame of this sequence contained 546 bp and encoded 181 amino acids, including a cystatin domain without the canonical binding site for cysteine proteinases and a bradykinin domain. Our results suggested that in lampreys and most of other vertebrates, there might be only one kininogen gene, which was fused by certain sequences during vertebrate evolution and encoded proteins with more functions; however, another special kininogen gene, only encoding the bradykinin domain with multiple copies in some species, arose only in amphibians for adapting themselves to the unique environment. Using reverse transcription PCR, kininogen mRNA was also detected in lamprey gut, kidney, and leukocyte, but absent in lamprey buccal gland. Our findings may provide insights into the phylogeny of kininogen genes as well as other gene families in vertebrates.

Fine mapping and candidate gene analysis of a green-revertible albino gene gra(t) in rice

Tao Chen, Yadong Zhang, Ling Zhao, Zhen Zhu, Jing Lin, Suobing Zhang, Cailin Wang

2009, 36(2): 117-123. doi: 10.1016/S1673-8527(08)60098-3

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Abstract:
Green-revertible albino is a novel type of chlorophyll deficiency in rice (Oryza sativa L.), which is helpful for further research in chlorophyll synthesis and chloroplast development to illuminate their molecular mechanism. In the previous study, we had reported a single recessive gene, gra(t), controlling this trait on the long arm of chromosome 2. In this paper, we mapped the gra(t) gene using 1,936 recessive individuals with albino phenotype in the F₂ population derived from the cross between themo-photoperiod-sensitive genic male-sterile (T/PGMS) line Pei'ai 64S and the spontaneous mutant Qiufeng M. Eventually, it was located to a confined region of 42.4 kb flanked by two microsatellite markers RM2-97 and RM13553. Based on the annotation results of RiceGAAS system, 11 open reading frames (ORFs) were predicted in this region. Among them, ORF6 was the most possible gene related to chloroplast development, which encoded the chloroplast protein synthesis elongation factor Tu in rice. Therefore, we designated it as the candidate gene of gra(t). Sequence analysis indicated that only one base substitution C to T occurred in the coding region, which caused a missense mutation (Thr to Ile) in gra(t) mutant. These results are very valuable for further study on gra(t) gene.

2009 Vol. 36, No. 2