Gene Amplification Process Research Articles

Maternal Spargel/dPGC-1 is critical for embryonic development and influences chorion gene amplification via Cyclin E activity

The function of spargel/dPGC-1 in Drosophila oogenesis has been unequivocally established. Here, we sought to assess whether Spargel protein or RNA is essential for developmentally competent eggs. The trans-heterozygotic combination of two spargel mutant alleles allowed us to decrease Spargel expression to very low levels. Using this model, we now demonstrated the requirement for Spargel in eggshell patterning and embryonic development, which led us to establish that spargel is a maternal effect gene. Further examination of Spargel's potential mechanism of action in eggshell biogenesis revealed that low levels of Spargel in the adult ovary cause diminished Cyclin E activity, resulting in reduced chorion gene amplification levels, leading to eggshell biogenesis defects. Thus, another novel role for spargel/dPGC-1 is exposed whereby, through Cyclin E activity, this conserved transcriptional coactivator regulates the chorion gene amplification process.

Nucleic Acid Amplification Free-QCM-DNA Biosensor for Burkholderia pseudomallei Detection.

Burkholderia pseudomallei is a gram-negative bacterium that causes the infectious disease melioidosis, a disease that can still be fatal despite appropriate treatment. The bacterium contains the gene clusters for the type III secretion system (TTSS), which are essential for its pathogenicity. This gene was often employed for accurate diagnosis through the laborious process of gene amplification. This work intends to develop a quartz crystal microbalance (QCM)-based TTSS gene detection method without gene amplification approaches to simplify the diagnosis process. In this study, it was demonstrated that a 540bp sequence flanked by BglI restriction sites within the TTSS1 on the B. pseudomallei genome is an effective target for specific detection of the bacteria. After cultivation and genome extraction, the bacteria can be detected by digesting its genome with BglI in which the TTSS1 fragment is detected by a QCM-DNA biosensor, eliminating the need for nucleic acid amplification. A specific probe designed to bind to the TTSSI fragment was utilized as the receptor on the QCM-DNA biosensor which provided the ability to detect the fragment. The limit of detection of the QCM-DNA biosensor was 0.4µM of the synthetic DNA target oligonucleotide. The system was also capable of specifically detecting the BglI digested-DNA fragment of B. pseudomallei species with significantly higher signal than B. thailandensis. This study provides evidence for an effective QCM-DNA biosensor that can identify B. pseudomallei without the need for nucleic acid amplification.

Molecular Characterization of Salmonella Species Isolated from Animal Sources in Southern-Taraba State, North-East Nigeria

Aims: The purpose of this research was to detect the Salmonella invA gene from chicken’s droppings in Southern Taraba, North East Nigeria. The invasive “invA” gene facilitates the invasion of epithelial cells by Salmonella isolates.
 Study Design: This study is experimental research involving ninety-eight (98) Salmonella isolates from chicken droppings in poultry farms and domestic chicken coops.
 Place and Duration of Study: This research was carried out in Wukari, Donga, Ibi and Takum towns in Southern Taraba, North East Nigeria between November 2021 and May 2023. A total of 400 (Donga,100; Wukari, 100; Ibi, 100 and Takum, 100) Chicken droppings were collected from 40
 (Donga, 10; Wukari, 10; Ibi, 10 and Takum, 10) small-scale poultry farms, and 100 (Donga, 25; Wukari, 25; Ibi, 25 and Takum, 25) Chicken droppings were sampled from 20 (Donga, 5; Wukari, 5; Ibi, 5 and Takum 5) domestic chicken coops and analyzed.
 Methodology: Using standard microbiological techniques, Salmonella Shigella Agar (SSA) was used to confirm and validate 98 (Wukari; 36, Donga; 19, Ibi; 27, and Takum; 16) Salmonella isolates from stock culture. Isolates were further subjected to biochemical analysis. Boiling technique was used to extract the DNA of the 98 isolates. Salmonella invA gene amplification process was done using Polymerase Chain Reaction (PCR). Electrophoresis was done using agarose gel, and DNA band patterns were visualized with the aid of ultraviolent light (UV) showing different patterns and interpreted with the 100 bp DNA ladder.
 Results: The results of this study indicate that the invA gene was detected in 80.6% (Wukari; 86.1%, Donga; 68.5%, Ibi;85.2%, and Takum; 75%) of the 98 Salmonella isolates with an amplicon size of 284bp. This finding implies that 19 isolates which did not show the targeted band are not invasive, and even if they are, other invasive genes may be liable.
 Conclusion: The detection of the invasive invA invasive gene from Salmonella isolates from the fecal droppings of apparently healthy chickens from poultry farms and domestic chicken coops is really of great concern to public health. Unless a proper hygienic protocol and biosecurity measures are strictly adhered to where applicable in food processing chain, Salmonella isolates harboring the invA traits could be opportunistically invasive among immunocompromised individuals and children.

Molecular diagnostics for clinical respiratory virus on a total integrated centrifugal microsystem using reverse transcription-loop-mediated isothermal amplification

Respiratory viruses are highly contagious agents that can cause endemic and epidemic infections in humans. Early detection of these viruses is crucial in preventing economic damage and reducing mortality rates. In this study, we present a total integrated genetic analyzer to perform a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay for the simultaneous detection of 7 respiratory viruses (Influenza A H1N1 and H3N2, Influenza B, Respiratory syncytial virus A and B, Adenovirus, and COVID-19). The primer sets for the RT-LAMP assay were designed and evaluated in comparison with the RT-PCR assay using clinical samples, confirming high specificity and efficiency. The entire process of viral RNA extraction, reagent mixing, gene amplification, and detection was completed on the device in 1 hr 20 min. The constructed portable diagnostic instrument is equipped with a rotary motor, two sets of peltier heaters, a fluorescence detector, and a touch screen for inputting experimental parameters and displaying result. The proposed point-of-care (POC) diagnostic platform correctly analyzed a total of 21 clinical samples (3 for each of the 7 viruses). The limit-of-detection (LOD) for Influenza A subtype H3N2 was 101 pfu/mL, which demonstrates the high performance of our proposed centrifugal microsystem for on-site molecular diagnostics in medical centers.

Identifikasi Molekular Kekerabatan Genetik Kopi Wamena Berbasis Marka Random Amplified of Polymorphic DNA (RAPD)

Baliem Coffee or Wamena Arabica Coffee is classified as a specialty coffee that has a distinctive aroma and taste as one of the world's best coffees. Wamena coffee has a high commercial value, there are many advantages of Wamena coffee. Growing on a variety of soil types, elevation, coffee variety, and durable. The quality of Wamena coffee must be maintained by the local government. However, this elite coffee germplasm is threatened with extinction and is in a dangerous situation due to habitat destruction due to forest clearing, land use change and the potential for competition with various disease-resistant varieties. This study aims to identify molecularly the genetic relationship of Wamena Arabica coffee in Jayawijaya district with the Random Amplified Polymorphic DNA (RAPD) markers as molecular markers. The stages in this study were sample collection, morphological observations, genomic DNA extracted using the CTAB method, gene amplification process using PCR-RAPD molecular markers with ten primers, measurement of DNA concentration using a spectrophotometer, and data analysis using UPGMA NTSYS version 2.1. The electroferogram results showed that pRAPD1, pRAPD2 and pRAPD5 primers produced a band pattern with high polymorphism as well as indicating the genetic diversity of the Coffea arabica L. arabica coffee samples tested. Based on the dendogram construction analysis, the arabica coffee sample Coffea arabica L. which was tested on 5 coffee genotypes, obtained 2 coffee groups, namely Group 1 consisting of one variety, namely sample (V) Arabica Typica from the Assolokobal area. Group 2 with four varieties, namely samples (I) Arabica Catimor, (II) USDA, (III) Arabica PM 88, and (IV) Arabica Linies 795, from Wollo. Phylogenetic tree construction resulted in a similarity coefficient of 83%, indicating the high relationship between Arabica coffee populations. The results of this study have obtained a genetic fingerprint profile of wamena specialty arabica coffee, namely its genetic relationship. The superiority of the genetic composition of Wamena coffee in Jayawijaya district in the future has the potential to be derived through much more advanced molecular technology.

Automated DNA Extraction Monitoring System Based on MTConnect Technology

MTConnect standard technology provides simplicity, flexibility, and scalability in integrating various equipment and operating systems and enabling accurate and consistent data collection from any MTConnect-compatible system. Using MTConnect technology, it is possible to immediately identify the cause of a problem and respond quickly when a problem occurs. Molecular genetic diagnostic point-of-care testing (POCT) devices have received attention in recent years because they enable rapid disease diagnosis. A molecular genetic diagnostic POCT device is under development by the authors. The system consists of a gene extraction process and a real-time PCR-based gene amplification process. In this study, we propose and demonstrate a system based on MTConnect technology to monitor an automated DNA extraction process. The proposed system consists of an automated DNA extraction system, an MTConnect adapter, an MTConnect agent, and a client application. The adapter and agent were developed on a Raspberry Pi single-board computer. The agent publishes the collected data in Extensible Markup Language (XML) format over a network. The performance and reliability of the system were evaluated by verifying the request response time between the implemented system’s agent and the client application. The results demonstrate the feasibility of monitoring the DNA extraction process over a network.

Efficient Development of Stable Recombinant Chinese Hamster Ovary (rCHO) Cell Lines to Produce Antibodies by Using Dimethyl Sulfoxide (DMSO) in Electroporation.

Development of stable rCHO cell lines is still time consuming and labor intensive, although it is a critical step in the commercial development of recombinant antibodies. The current work demonstrates, for the first time, that electroporation of CHO cells with DMSO can enhance stable expression of recombinant antibodies in rCHO cells. Electroporation with DMSO resulted in an average 3.7-fold and 2.8-fold increases in expression levels of aflibercept and pembrolizumab, respectively, in pools of stable rCHO cells. It also resulted in an average of 2.2-fold and 2.6-fold increases in the expression of aflibercept and pembrolizumab, respectively, in single-cell derived rCHO clones. Simple batch cultures of rCHO cell clones with the highest expression produced 1.0 g/l for aflibercept and 1.4 g/l for pembrolizumab without a time-consuming gene amplification process. Electroporation with DMSO also shortened the development of rCHO cell lines to 2-3 months, allowing rapid establishment of stable rCHO cell lines with a desirable expression level antibodies.

Beyond DNA puffs: What can we learn from studying sciarids?

Members of the Sciaridae family attracted the interest of researchers because of the demonstration that the DNA puff regions, which are formed in the salivary gland polytene chromosomes at the end of the fourth larval instar, constitute sites of developmentally regulated gene amplification. Besides contributing to a deeper understanding of the process of gene amplification, the study of sciarids has also provided important insights on other biological processes such as sex determination, programmed cell death, insect immunity, telomere maintenance, and nucleolar organizing regions (NOR) formation. Open questions in sciarids include among others, early development, the role of noncoding RNAs in gene amplification and the relationship between gene amplification and transcription in DNA puff forming regions. These and other questions can now be pursued with next generation sequencing techniques and experiments using RNAi experiments, since this latter technique has been shown to be feasible in sciarids. These new perspectives in the field of sciarid biology open the opportunity to consolidate sciarid species as important emerging models. genesis 54:361-378, 2016. © 2016 Wiley Periodicals, Inc.

Construction of Vector for Functional Analysis of the Intrinsically Bent DNA in the ACE3 Replicator from <i>Drosophila melanogaster</i>

DNA replication is a crucial process for species survival, nevertheless it is not clear which factors define origin selection in multicellular eukaryotes. Developmental gene amplification systems, such as the one described during ovarian follicles development in Drosophila melanogaster, are useful tools for studying of DNA replication process in these organisms. We previously described that the well characterized third chromosome amplified domain of D. melanogater displays three intrinsically bent DNA sites: b1, localized at an amplification control element (ACE3), b2 and b3, both localized at the preferential origin ori-β. This proposal aimed to construct a Drosophila transformation vector, which contains a short deletion at the ACE3, in order to reduce the intrinsically bent DNA site b1, and analyze the functional role of this site in the gene amplification process. Through a series of cloning steps, we obtained a Big Parent vector derivative, containing a deletion at the positions 176-180 bp, inside the ACE3. The generation of a Drosophila transformation vector displays a reduced intrinsically bent DNA site in the third chromosome amplified domain, it will allow the analysis of the functional role of this curvature in developmental gene amplification, providing new insights on replication initiation in D. melanogaster and the function of intrinsically bent DNA sites.

An on-chip RT-PCR microfluidic device, that integrates mRNA extraction, cDNA synthesis, and gene amplification

This paper presents an on-chip integrated reverse transcriptase polymerase chain reaction (RT-PCR) microchip, which integrates the genetic functionalities of messenger ribonucleic acid (mRNA) extraction, complementary deoxyribonucleic acid (cDNA) synthesis, and gene amplification. The proposed RT-PCR microchip consists of a RNA microchannel for extracting mRNA from lysate biological samples, and a DNA microchamber for synthesizing cDNA and amplifying the target gene. As magnetic oligo-dT beads are passed through the RNA microchannel, mRNA bound to the beads was extracted within 1 min by a ferromagnetic wire array inlaid in the RNA microchannel. In the DNA microchamber, the extracted bound mRNA was used for direct synthesis of cDNA followed by amplification of the target gene. To evaluate the performance of the RT-PCR microchip, RT-PCR analyses were performed using various volumes of blood and numbers of breast cancer cells. Additionally, to verify the feasibility of the RT-PCR microchip for clinical applications, it was used for detection of virus-specific genes from specimens of patients infected with respiratory viruses. The continuous and integrated mRNA extraction, cDNA synthesis, and gene amplification process enabled by the proposed RT-PCR microchip suggests its use for high-precision genetic assays with small sample quantities.

Generation of high-producing cell lines by overexpression of cell division cycle 25 homolog A in Chinese hamster ovary cells

To improve the efficiency of conventional gene amplification systems, the effect of cell cycle modification during the gene amplification process on IgG production was investigated in Chinese hamster ovary (CHO) cells. The full-length cDNA of CHO cell division cycle 25 homolog A (Cdc25A) was introduced into CHO DG44 cells and the effects of CDC25A overexpression on the cell cycle, transgene copy number and IgG productivity were examined. Both wild-type and mutated CDC25A-overexpressing CHO cells showed a rapid increase in transgene copy number compared with mock cells during the gene amplification process, in both cell pools and individual clones. High-producing clones were obtained with high frequency in CDC25A-overexpressing cell pools. The specific production rate of the isolated clone CHO SD-S23 was up to 2.9-fold higher than that of mock cells in the presence of 250 nM methotrexate (MTX). Cell cycle analysis revealed that the G2 to M phase transition rate was increased ∼1.5-fold in CDC25A-overexpressing CHO cells under MTX treatment. Our results show the improvement of conventional gene amplification systems via cell cycle engineering at an early stage of cell line development.

Advances in Mammalian Cell Line Development Technologies for Recombinant Protein Production

From 2006 to 2011, an average of 15 novel recombinant protein therapeutics have been approved by US Food and Drug Administration (FDA) annually. In addition, the expiration of blockbuster biologics has also spurred the emergence of biosimilars. The increasing numbers of innovator biologic products and biosimilars have thus fuelled the demand of production cell lines with high productivity. Currently, mammalian cell line development technologies used by most biopharmaceutical companies are based on either the methotrexate (MTX) amplification technology or the glutamine synthetase (GS) system. With both systems, the cell clones obtained are highly heterogeneous, as a result of random genome integration by the gene of interest and the gene amplification process. Consequently, large numbers of cell clones have to be screened to identify rare stable high producer cell clones. As such, the cell line development process typically requires 6 to 12 months and is a time, capital and labour intensive process. This article reviews established advances in protein expression and clone screening which are the core technologies in mammalian cell line development. Advancements in these component technologies are vital to improve the speed and efficiency of generating robust and highly productive cell line for large scale production of protein therapeutics.

Rapid construction of transgene-amplified CHO cell lines by cell cycle checkpoint engineering

The process of establishing high-producing cell lines for the manufacture of therapeutic proteins is usually both time-consuming and laborious due to the low probability of obtaining high-producing clones from a pool of transfected cells and slow cell growth under the strong selective pressure of screening to identify high-producing clones. We present a novel method to rapidly generate more high-producing cells by accelerating transgene amplification. A small interfering RNA (siRNA) expression vector against ataxia telangiectasia and Rad3 related (ATR), a cell cycle checkpoint kinase, was transfected into Chinese hamster ovary (CHO) cells. The influences of ATR downregulation on gene amplification and the productivity were investigated in CHO cells producing green fluorescent protein (GFP) and secreting monoclonal antibody (mAb). The ATR-downregulated cells showed up to a 6-fold higher ratio of GFP-positive cells than that of the control cell pool. Moreover, the downregulated mAb-producing cells had about a 4-fold higher specific production rate and a 3-fold higher volumetric productivity as compared with the mock cells. ATR-downregulated cells showed a much faster increase in transgene copy numbers during the gene amplification process via methotrexate (MTX) treatment in both GFP- and mAb-producing cells. Our results suggest that a pool of high-producing cells can be more rapidly generated by ATR downregulation as compared with conventional gene amplification by MTX treatment. This novel method may be a promising approach to reduce time and labor in the process of cell line development.

Unstable expression of recombinant antibody during long-term culture of CHO cells is accompanied by histone H3 hypoacetylation

The gradual loss of recombinant protein expression in CHO cell lines during prolonged subculture is a common issue, referred to as instability, which seriously affects the industrial production processes of therapeutic proteins. Loss of recombinant gene copies, due to the genetic instability of CHO cells, and epigenetic silencing of transgene sequences, are the main reported causes of production instability. To increase our understanding on the molecular mechanisms inherent to CHO cells involved in production instability, we explored the molecular features of stable and unstable antibody producing cell lines obtained without gene amplification, to exclude the genetic instability induced by the gene amplification process. The instability of recombinant antibody production during long-term culture was caused by a 48-53% decrease in recombinant mRNA levels without significant loss of recombinant gene copies, but accompanied by a ~45% decrease in histone H3 acetylation (H3ac). Thus, our results suggest a critical role of H3ac in the stability of recombinant protein production.

Poxvirus Use a “Gene Accordion” to Tune Out Host Defenses

A multistep process of gene amplification, mutation, and reduction allows poxvirus to overcome host antiviral defenses. The mechanism speeds genetic adaptation and promises to be broadly applicable in many biological settings.

Gene amplification in breast cancer – looking for the molecular mechanisms

Amplification of genes in breast cancer cells was shown to be coordinated in the majority of cases assuming the presence of common undisclosed mechanism underlying intrachromosomal gene amplification process. Overexpression and amplification of the HER-2/neu gene is observed in 20–30% of breast cancer cases and predicts more frequent relapse and shorter survival time. However, the initial events and molecular mechanisms of chromosomal aberrations in the region around HER2/neu as well as the precise boundaries of amplified regions remain to be obscure. This study was an attempt to define the boundaries of amplified chromosome 17q12-q21 region around HER2/neu gene. Structural peculiarities of amplification boundary regions were investigated by various techniques. Gene dosage analysis was performed for several genes located around HER2/neu gene in 154 breast cancer tissue samples. The copy number of the ppparbp, her2/neu, znfn1a3 Casc3 and top2a genes were analyzed by comparative TaqMan real time PCR. Fifty six samples (36 %) were found to be her2/neu-amplified (NHER2/neu ≥ 1,5), the boundaries for HER2-containing amplicons were mapped. Observed results suggest that similar positions of amplified region boundaries in different breast cancer samples are not accidental and may be related with the DNA structural and/or sequence peculiarities of boundary regions. Trying to find “special” sequences at the amplicon boundaries, we performed the analysis of sequence flexibility in the region TBC1D3– HER2/neu – TOP2A using the TwistFlex program. The analysis revealed several high flexible sequences in SOCS7, FBX047, HER2/neu and ZNFN1A3 genes. The locations of amplified region boundaries in 30% of cases were inside ZNFN1A3 gene. Organization of DNA sequence and nucleotide composition of FlexZNF-1 and FlexZNF-2 were similar to AT-rich islands of common fragile site (FS). Sequences of FlexZNF-1 and FlexZNF-2 have strong potential to form secondary structures according to the analysis by Mfold software (GCG Wisconsin PackageTM). Thus, the analysis of DNA sequence in TBC1D3– HER2/neu – TOP2A region revealed the existence of two flexible sequences in the ZNFN1A3 gene sequence with the strong potential to form stable secondary structures which may affect normal DNA replication at these sites and result in DNA double strand break appearance. The location of FlexZNF-1 and FlexZNF-2 strongly coincided with the location of amplified around HER2/neu gene fragment boundaries observed by real time PCR analysis. This observation indicates involvement of Flex sites in the process of intrachromosomal DNA amplification.

Dihydrofolate reductase amplification and sensitization to methotrexate of methotrexate-resistant colon cancer cells

Gene amplification is one of the most frequent manifestations of genomic instability in human tumors and plays an important role in tumor progression and acquisition of drug resistance. To better understand the factors involved in acquired resistance to cytotoxic drugs via gene amplification, we have analyzed the structure and dynamics of dihydrofolate reductase (DHFR) gene amplification in HT29 cells treated with methotrexate (MTX). Analysis of the DHFR gene amplification process shows that the amplicon exhibits a complex structure that is consistently reproduced in independent treatments. The cytogenetic manifestation of the amplification in advanced stages of the treatment may be in the form of double minutes or as a homogeneously stained region. To get insights into the mechanisms of resistance, we have also investigated the sensitization to MTX of MTX-resistant cells after drug withdrawal and reexposure to MTX. Passive loss of the DHFR amplicon by withdrawal of the drug results in MTX-sensitive cells exhibiting a substantial reduction of their capacity or even an incapacity to generate resistance when submitted to a second cycle of MTX treatment. On a second round of drug administration, the resistant cells generate a different amplicon structure, suggesting that the formation of the amplicon as in the first cycle of treatment is not feasible. These results indicate that DHFR gene amplification is a "wear and tear" process in HT29 cells and that MTX-resistant cells may become responsive to a second round of treatment if left untreated during a sufficient period of time.

Cytogenetic and Molecular Analysis Aspects on some Local Romanian Bombyx mori Races

SUMMARY About 3000 distinct genotypes of Bombyx mori - an excellent model for Genomicssituates this species on second place after Drosophila , as an insect model for studying heredity which started in Japan, at the beginning o f XIX th century. The appearance of some local B. mori races in Romania imposed the necessity of studying them under cytogenetic and molecular aspects for their precise identification. The analyses done on six Romanian B. mori races employing some classic cytogenetics methods (aceto-carmine, DAPI and Giemsa staining) have demonstrated normal meiotic and mitotic chromosomal complements (n=28; 2n=56) as well as in some cases hypoand hyper-ploidy. Using TEM (transmission electron microscopy) technique, the synaptonemal complexes in pachytene-diplotene stages were detected. In silk-glands of IV th stage larvae, the polyteny phenomenon was described associated with the ribosomal gene amplification process visualized as a plethora of R NPs (ribonucleoprotein particles) of different sizes and shapes. The chromosomal bivalen ts in different stages of meiosis, with a typical structure and behavior, were identified. Optimization and implementation of modern molecular methods, as well as the study of some molecular markers (RAPD-RFLP) allowed us to obtain different electrophoretic patterns valuable for differentiating and identific ation of the studied races. All electrophoretic patterns obtained from PCR-RAPD reaction with OPA4 , OPA7 , OPA8 , P1 , P4 and P5 primers followed by RFLP reaction using HaeIII enzyme proved to be different, so that each studied race could be discr iminated. Applying molecular methods can be helpful in the br eeding process of silkworms assisted by classical and modern molecular genetics approaches.

Statistical models in assessing fold change of gene expression in real-time RT-PCR experiments

Real-time RT-PCR has been frequently used in quantitative research in molecular biology and bioinformatics. It provides remarkably useful technology to assess expression of genes. Although mathematical models for gene amplification process have been studied, statistical models and methods for data analysis in real-time RT-PCR have received little attention. In this paper, we briefly introduce current mathematical models, and study statistical models for real-time RT-PCR data. We propose a generalized estimation equations (GEE) model that properly reflects the structure of repeated data in RT-PCR experiments for both cross-sectional and longitudinal data. The GEE model takes the correlation between observations within the same subjects into consideration, and prevents from producing false positives or false negatives. We further demonstrate with a set of actual real-time RT-PCR data that different statistical models yield different estimations of fold change and confidence interval. The SAS program for data analysis using the GEE model is provided to facilitate easy computation for non-statistical professionals.

Chaotic behavior of semigroups related to the process of gene amplification–deamplification with cell proliferation

In the last few years there has been a renewed interest in infinite systems of differential equations, similar to the classical birth-and-death system of population dynamics, due to their rôle in modelling the evolution of drug resistance in cancer cells. In [J. Banasiak, M. Lachowicz, Topological chaos for birth-and-death models with proliferation, Math. Models Methods Appl. Sci. 12 (6) (2002) 755] such systems were shown to generate a chaotic dynamics under, however, very restrictive assumptions on the growth of coefficients. In this paper, using recently developed concept of subspace chaos [J. Banasiak, M. Moszyński, A generalization of Desch–Schappacher–Webb criteria for topological chaos with applications, Discrete Contin. Dyn. Syst. – A 12 (5) (2005) 959], we show that for a linear growth of the coefficients, which are more acceptable from biological point of view, the dynamics of these systems is chaotic in some subspaces of the original state space.