Exploring the molecular basis of heterosis for plant breeding

Since approximate a century ago, many hybrid crops have been continually developed by crossing two inbred varieties. Owing to heterosis(hybrid vigor) in plants, these hybrids often have superior agricultural performances in yield or disease resistance succeeding their inbred parental lines. Several classical hypotheses have been proposed to explain the genetic causes of heterosis. During recent years, many new genetics and genomics strategies have been developed and used for the identifications of heterotic genes in plants. Heterotic effects of the heterotic loci and molecular functions of the heterotic genes are being investigated in many plants such as rice, maize, sorghum, Arabidopsis and tomato.More and more data and knowledge coming from the molecular studies of heterotic loci and genes will serve as a valuable resource for hybrid breeding by molecular design in future. This review aims to address recent advances in our understanding of the genetic and molecular mechanisms of heterosis in plants. The remaining scientific questions on the molecular basis of heterosis and the potential applications in breeding are also proposed and discussed.     

Biochemical and physiological basis of heterosis

The phenomenon of heterosis or hybrid vigor has long been recognized to have a genetic basis. Heterosis expressed in hybrids often has been correlated with the heterozygosity inherent to a hybrid produced from the cross of parents of different genetic backgrounds. Our understanding of the molecular mechanisms that elicit heterosis remains incomplete; however, a number of critical experiments have contributed to our understanding of the physiological processes and biochemical mechanisms operative in the expression of heterosis. These experiments and the genetic mechanisms thought to underlie them are considered here. Based upon these findings, heterosis does not appear to have a single cause, but rather may result by reason of the action of either single or multiple genes’ in the nucleus or the cytoplasm or both. Pertinent examples of gene action which potentiates heterotic effects are discussed.     

Mycoplasma fermentans interaction with monocytes/macrophages: molecular basis

Mycoplasmas are the smallest free-living self-replicating bacteria - having diameters of 200 to 800 nm - widely distributed in animals and plants. Mycoplasma fermentans is a human pathogen suspected to be involved in the progression of autoimmune diseases. Although pathogenesis mechanisms of M. fermentans are currently poorly understood, the role of these microorganisms as immunomodulatory agents is well established. In the present paper, we will review and discuss recent breakthroughs in the field.     

Losartan's molecular basis of interaction with membranes and AT1 receptor

Physicochemical methods were used to study the thermal and dynamic changes caused by losartan in the membrane bilayers. In addition, molecular modeling was implemented to explore its topography both in membranes and AT(1) receptor. Its incorporation resulted in the modification of thermal profile of dipalmitoyl phosphatidylcholine (DPPC) bilayers in a concentration dependent way up to 20mol% as it is depicted from the combination of differential scanning calorimetry (DSC) and MAS data. In particular, the presence of losartan caused lowering of the phase transition temperature and abolishment of the pretransition. T(1) experiments revealed the location of the drug into the membrane bilayers. The use of a combination of biophysical methods along with docking experiments brought out a possible two-step mechanism which involves incorporation of losartan at the interface of membrane bilayers and diffusion in the upper parts of AT(1) receptor helices IV-VII.     

Enriched partial correlations in genome-wide gene expression profiles of hybrids (A. thaliana): a systems biological approach towards the molecular basis of heterosis

Heterosis is a well-known phenomenon but the underlying molecular mechanisms are not yet established. To contribute to the understanding of heterosis at the molecular level, we analyzed genome-wide gene expression profile data of Arabidopsis thaliana in a systems biological approach. We used partial correlations to estimate the global interaction structure of regulatory networks. Our hypothesis states that heterosis comes with an increased number of partial correlations which we interpret as increased numbers of regulatory interactions leading to enlarged adaptability of the hybrids. This hypothesis is true for mid-parent heterosis for our dataset of gene expression in two homozygous parental lines and their reciprocal crosses. For the case of best-parent heterosis just one hybrid is significant regarding our hypothesis based on a resampling analysis. Summarizing, both metabolome and gene expression level of our illustrative dataset support our proposal of a systems biological approach towards a molecular basis of heterosis.     

A molecular basis for estrogen-induced cryptorchidism

Male sexual differentiation relies upon testicular secretion of the hormones testosterone, Mullerian inhibiting substance, and insulin-3 (Insl3). Insl3 is responsible for testicular descent through virilization and outgrowth of the embryonic gubernaculum. In mouse, prenatal exposure to 17beta-estradiol and the nonsteroidal synthetic estrogen diethylstilbestrol (DES) disturbs the endocrine balance, causing demasculinizing and feminizing effects in the male embryo, including impaired testicular descent (cryptorchidism). In the current study, we show that maternal exposure to estrogens, including 17alpha- and beta-estradiol, as well as DES, specifically down regulates Insl3 expression in embryonic Leydig cells, thereby providing a mechanism for cryptorchidism. These experiments may have implications for the widespread use of estrogenic substances in agriculture and the environment.     

The molecular basis of the antiplatelet action of ajoene: direct interaction with the fibrinogen receptor

Ajoene, the major antiplatelet compound derived from garlic inhibits the fibrinogen-supported aggregation of washed human platelets (ID50 = 13 microM) and, inhibits binding of 125I-fibrinogen to ADP-stimulated platelets (ID50 = 0.8 microM). In both cases, the inhibition is of the mixed non-competitive type. Furthermore, fibrinogen-induced aggregation of chymotrypsin-treated platelets is also inhibited by ajoene in a dose-dependent manner (ID50 = 2.3 microM). Other membrane receptors such as ADP or epinephrine receptors are not affected by ajoene. Ajoene strongly quenches the intrinsic fluorescence emission of purified glycoproteins IIb-IIIa (ID50 = 10 microM). These results indicate that the antiaggregatory effect of ajoene is causally related to its direct interaction with the putative fibrinogen receptor.     

Importance of over-dominance as the genetic basis of heterosis in rice

In populations derived from commercial hybrid rice combination Shanyou 10, F₁ heterosis and F₂ inbreeding depression were observed on grain yield (GYD) and number of panicles (NP). Using marker loci evenly distributed on the linkage map as fixing factors, the F₂ population was divided into sub-populations. In a large number of sub-populations, significant correlations were observed between heterozygosity and GYD, and between heterozygosity and NP. This was especially true in type III sub-populations in which the genotype of a fixing factor was heterozygotes. In type III sub-populations, 15 QTL for GYD and 13 QTL for NP were detected, of which the majority exhibited over-dominance effects for increasing the trait values. This study showed that over-dominance played an important role in the genetic control of heterosis in rice.     

Molecular basis of Bcl-X(L)-p53 interaction: insights from molecular dynamics simulations

Bcl-X(L), an antiapoptotic Bcl-2 family protein, plays a central role in the regulation of the apoptotic pathway. Heterodimerization of the antiapoptotic Bcl-2 family proteins with the proapoptotic family members such as Bad, Bak, Bim and Bid is a crucial step in the apoptotic regulation. In addition to these conventional binding partners, recent evidences reveal that the Bcl-2 family proteins also interact with noncanonical binding partners such as p53. Our previous NMR studies showed that Bcl-X(L): BH3 peptide and Bcl-X(L): SN15 peptide (a peptide derived from residues S15-N29 of p53) complex structures share similar modes of bindings. To further elucidate the molecular basis of the interactions, here we have employed molecular dynamics simulations coupled with MM/PBSA approach. Bcl-X(L) and other Bcl-2 family proteins have 4 hydrophobic pockets (p1-p4), which are occupied by four systematically spaced hydrophobic residues (h1-h4) of the proapoptotic Bad and Bak BH3 peptides. We observed that three conserved hydrophobic residues (F19, W23 and L26) of p53 (SN15) peptide anchor into three hydrophobic pockets (p2-p4) of Bcl-X(L) in a similar manner as BH3 peptide. Our results provide insights into the novel molecular recognition by Bcl-X(L) with p53.     

Importance of over-dominance as the genetic basis of heterosis in rice

In populations derived from commercial hybrid rice combination Shanyou 10, F1 hetero-sis and F2 inbreeding depression were observed on grain yield (GYD) and number of panicles (NP). Using marker loci evenly distributed on the linkage map as fixing factors, the F2 population was divided into sub-populations. In a large number of sub-populations, significant correlations were observed between heterozygosity and GYD, and between heterozygosity and NP. This was especially true in type III sub-populations in which the genotype of a fixing factor was heterozy-gotes. In type III sub-populations, 15 QTL for GYD and 13 QTL for NP were detected, of which the majority exhibited over-dominance effects for increasing the trait values. This study showed that over-dominance played an important role in the genetic control of heterosis in rice.