Henry Heng

Last updated
Henry Heng
Alma mater University of Toronto
Known forStudies in genomics, evolutionary biology, cancer evolution
Awards PROSE Awards finalist
2020 Wayne State Board of Governors’ award
Scientific career
Institutions

Henry HQ Heng is a professor of molecular medicine and genetics and of pathology at the Wayne State University School of Medicine. Heng first received his PhD from the University of Toronto Hospital for Sick Children in 1994, mentored by Lap-Chee Tsui. He then completed his post-doc under Peter Moens at York University, before joining the Wayne State University School of Medicine faculty. [1]

Contents

Heng's lab is dedicated to researching a wide variety of topics ranging from genomics, evolution, and cancer, using their new framework: the Genome Architecture Theory (GAT). The Genome Architecture Theory focuses more on a genome or chromosome-oriented approach to biology, in contrast to the traditional gene-oriented approach. Major tenets of the framework include genome topology, the idea that there is an emergent level of information from the order of genes on a chromosome, two-phased evolution, a model of evolution proposing a punctuated and gradual phase in evolution using cancer evolution as a model, and genome chaos, an overarching phenomenon of genomic instability that results from stress and can rearrange the genome, characterized by non-clonal chromosomal aberrations (NCCAs). [2]

In 2015, he wrote his first book, Debating Cancer: The Paradox in Cancer Research. His second book, Genome Chaos: Rethinking Genetics, Evolution, and Molecular Medicine, published in 2019, was a PROSE Awards finalist in 2020. [3] For his book, he was presented the 2020 Wayne State Board of Governors’ award. [4]

He formerly served as co-editor-in-chief of the journal Molecular Cytogenetics . [5]

Two-phased cancer evolution

Heng proposed a two-phased model of cancer evolution alternating between a punctuated macroevolutionary phase and a gradual microevolutionary phase. [6] In the macroevolutionary phase, the stress-induced rapid genome reorganization creates new system information essential for system survival. [7] In the microevolutionary phase, more minor gene-level adaptations promote population growth. Importantly, this model implies that the stepwise accumulation of microevolution over time does not equate to macroevolution. A two-phased evolutionary model can be extended to organismal evolution as well, as cancer offers an effective platform to study the mechanisms of evolution. [8] [9] [10]

Karyotype coding

To understand the creation and maintenance of system information for complexity and diversity in biology, Heng coined the term ‘karyotype code.’ This idea presents the karyotype as a code defined by genomic topology of all genes and other DNA sequences. Thus, the physical relationship of genes within a three-dimensional nucleus may change genetic expression without explicitly changing any genes. Karyotype coding differentiates ‘parts inheritance,’ or the inheritance of the gene level, from ‘system inheritance,’ which posits there are emergent properties in the genome that arise at a level above the gene. This framework highlights the importance of a genome organization-based information package and its implications for future genomic and evolutionary studies. [11]

Genome chaos

Genome chaos is another term proposed by Heng to describe the process of rapid genome re-organization during cellular crisis results in various chaotic genomes that display newly created system information. This phenomenon was occasionally observed in cytogenetic studies, and it was largely ignored until the establishment of a link between genome chaos and the punctuated phase of cancer evolution. [12] It was recently confirmed by sequencing across different cancer types, and has been described by a wide array of new terminology (including “chromothripsis,” “chromoplexy,” “chromoanagenesis,” “chromoanasynthesis,” “chromosome catastrophes,” “structural mutations,” “Frankenstein chromosomes,” and more). Despite the various individual molecular mechanisms can trigger genome chaos, acting as a cellular survival mechanism, the common consequence is the formation of new genomes ready for macroevolutionary selection. [13] [14] [15]

Fuzzy inheritance

Fuzzy inheritance is another term coined by Heng describing the heterogeneity and unpredictable relationship between genotype and phenotype. Traditionally, various non-clonal abnormal structures were insignificant “noise” and the results of bio-errors. To explain the mechanism of various types of heterogeneity, from gene to genome, including nongenomic types, Heng has proposed that the inheritance itself is heterogenous, even for a single gene. While the gene theory, which states that a gene codes for a specific, fixed phenotype, and the environmental impact on the genotype’s penetration, fuzzy inheritance suggests that most genes code for a range of potential phenotypes depending on the context provided by other genes and the environment. From this “fuzzy” range of potential phenotypes, the respective environment can then allow the best-suited status to be “chosen”. Such inheritance that codes for a range of phenotypes, not just a fixed phenotype, is named a fuzzy inheritance. Fuzzy inheritance can be observed at the gene, epigenetic, and genome levels. Furthermore, genome instability can increase the ‘fuzziness’ of inheritance, which is useful for cellular adaptation. [16] [17]

Function of sexual reproduction

When discussing the main function of sexual reproduction, a generally accepted viewpoint states that asexual reproduction produces identical copies and that the main function of sexual reproduction is to mix genes for the diversity necessary for evolutionary progression. By treating a species as a system, Heng suggests that mixing genes will not change a given system (species), rather that sexual reproduction promotes the continuation of a species by maintaining the chromosome-defined boundary or framework of a species. Heng proposes the main function of sexual reproduction as the preservation of the identity of a given genome rather than the promotion of genetic diversity as is commonly thought. [18] [19]

Genome architecture theory

To solve ever-increasing surprises in genomic research that challenge the gene theory, Heng has established the genome architecture theory (GAT) with 12 key principles including the concept of how genome reorganization, rather than new gene formation defines new species. According to the GAT, genome-level re-organizations create new species or systems (representing macro-evolution), while the gene or epigenetic levels of alteration modify a species (representing the micro-evolution). Heng asserts that the genome or karyotype is not simply a carrier of DNA but instead an organizer of genes. More precisely, by changing the network of genes that influence phenotype, without specifically changing the genes themselves, genomic topology changes can use karyotype changes to change phenotype. The relationship between gene mutations, epigenetic changes, and genome changes can be illustrated by a multiple-level landscape model where the local landscape represents gene/epigenetic status and the global landscape represents the status of genome replacement. Fundamentally, different bioprocesses require different types of inheritance, which should be studied in different landscapes. [20] [21]

High-resolution Fiber-FISH

Heng pioneered high-resolution FISH on released chromatin fibers that have revolutionized the FISH field. This system, now known as Fiber-FISH, has been extensively used for gene cloning, physical mapping, DNA replication, copy number variation (CNV), and genome structure studies. [22] [23]

Books

Related Research Articles

<span class="mw-page-title-main">Centromere</span> Specialized DNA sequence of a chromosome that links a pair of sister chromatids

The centromere links a pair of sister chromatids together during cell division. This constricted region of chromosome connects the sister chromatids, creating a short arm (p) and a long arm (q) on the chromatids. During mitosis, spindle fibers attach to the centromere via the kinetochore.

<span class="mw-page-title-main">Genetics</span> Science of genes, heredity, and variation in living organisms

Genetics is the study of genes, genetic variation, and heredity in organisms. It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar working in the 19th century in Brno, was the first to study genetics scientifically. Mendel studied "trait inheritance", patterns in the way traits are handed down from parents to offspring over time. He observed that organisms inherit traits by way of discrete "units of inheritance". This term, still used today, is a somewhat ambiguous definition of what is referred to as a gene.

<span class="mw-page-title-main">Heredity</span> Passing of traits to offspring from the species parents or ancestor

Heredity, also called inheritance or biological inheritance, is the passing on of traits from parents to their offspring; either through asexual reproduction or sexual reproduction, the offspring cells or organisms acquire the genetic information of their parents. Through heredity, variations between individuals can accumulate and cause species to evolve by natural selection. The study of heredity in biology is genetics.

Genomic imprinting is an epigenetic phenomenon that causes genes to be expressed or not, depending on whether they are inherited from the mother or the father. Genes can also be partially imprinted. Partial imprinting occurs when alleles from both parents are differently expressed rather than complete expression and complete suppression of one parent's allele. Forms of genomic imprinting have been demonstrated in fungi, plants and animals. In 2014, there were about 150 imprinted genes known in mice and about half that in humans. As of 2019, 260 imprinted genes have been reported in mice and 228 in humans.

Molecular evolution is the process of change in the sequence composition of cellular molecules such as DNA, RNA, and proteins across generations. The field of molecular evolution uses principles of evolutionary biology and population genetics to explain patterns in these changes. Major topics in molecular evolution concern the rates and impacts of single nucleotide changes, neutral evolution vs. natural selection, origins of new genes, the genetic nature of complex traits, the genetic basis of speciation, the evolution of development, and ways that evolutionary forces influence genomic and phenotypic changes.

<span class="mw-page-title-main">Y chromosome</span> Sex chromosome in the XY sex-determination system

The Y chromosome is one of two sex chromosomes in therian mammals and other organisms. Along with the X chromosome, it is part of the XY sex-determination system, in which the Y is the sex-determining because it is the presence or absence of Y chromosome that determines the male or female sex of offspring produced in sexual reproduction. In mammals, the Y chromosome contains the SRY gene, which triggers development of male gonads. The Y chromosome is passed only from male parents to male offspring.

<span class="mw-page-title-main">Molecular genetics</span> Scientific study of genes at the molecular level

Molecular genetics is a branch of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the structure and/or function of genes in an organism's genome using genetic screens. 

Gene duplication is a major mechanism through which new genetic material is generated during molecular evolution. It can be defined as any duplication of a region of DNA that contains a gene. Gene duplications can arise as products of several types of errors in DNA replication and repair machinery as well as through fortuitous capture by selfish genetic elements. Common sources of gene duplications include ectopic recombination, retrotransposition event, aneuploidy, polyploidy, and replication slippage.

<span class="mw-page-title-main">Chromosomal translocation</span> Phenomenon that results in unusual rearrangement of chromosomes

In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes balanced and unbalanced translocation, with two main types: reciprocal, and Robertsonian translocation. Reciprocal translocation is a chromosome abnormality caused by exchange of parts between non-homologous chromosomes. Two detached fragments of two different chromosomes are switched. Robertsonian translocation occurs when two non-homologous chromosomes get attached, meaning that given two healthy pairs of chromosomes, one of each pair "sticks" and blends together homogeneously.

<span class="mw-page-title-main">Index of evolutionary biology articles</span>

This is a list of topics in evolutionary biology.

<span class="mw-page-title-main">Comparative genomics</span>

Comparative genomics is a field of biological research in which the genomic features of different organisms are compared. The genomic features may include the DNA sequence, genes, gene order, regulatory sequences, and other genomic structural landmarks. In this branch of genomics, whole or large parts of genomes resulting from genome projects are compared to study basic biological similarities and differences as well as evolutionary relationships between organisms. The major principle of comparative genomics is that common features of two organisms will often be encoded within the DNA that is evolutionarily conserved between them. Therefore, comparative genomic approaches start with making some form of alignment of genome sequences and looking for orthologous sequences in the aligned genomes and checking to what extent those sequences are conserved. Based on these, genome and molecular evolution are inferred and this may in turn be put in the context of, for example, phenotypic evolution or population genetics.

<span class="mw-page-title-main">Human genetics</span> Study of inheritance as it occurs in human beings

Human genetics is the study of inheritance as it occurs in human beings. Human genetics encompasses a variety of overlapping fields including: classical genetics, cytogenetics, molecular genetics, biochemical genetics, genomics, population genetics, developmental genetics, clinical genetics, and genetic counseling.

Genetics, a discipline of biology, is the science of heredity and variation in living organisms.

<span class="mw-page-title-main">Locus (genetics)</span> Location of a gene or region on a chromosome

In genetics, a locus is a specific, fixed position on a chromosome where a particular gene or genetic marker is located. Each chromosome carries many genes, with each gene occupying a different position or locus; in humans, the total number of protein-coding genes in a complete haploid set of 23 chromosomes is estimated at 19,000–20,000.

<span class="mw-page-title-main">Genetic analysis</span>

Genetic analysis is the overall process of studying and researching in fields of science that involve genetics and molecular biology. There are a number of applications that are developed from this research, and these are also considered parts of the process. The base system of analysis revolves around general genetics. Basic studies include identification of genes and inherited disorders. This research has been conducted for centuries on both a large-scale physical observation basis and on a more microscopic scale. Genetic analysis can be used generally to describe methods both used in and resulting from the sciences of genetics and molecular biology, or to applications resulting from this research.

<span class="mw-page-title-main">Gene</span> Sequence of DNA or RNA that codes for an RNA or protein product

In biology, the word gene can have several different meanings. The Mendelian gene is a basic unit of heredity and the molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and non-coding genes.

<span class="mw-page-title-main">Chromosomal rearrangement</span>

In genetics, a chromosomal rearrangement is a mutation that is a type of chromosome abnormality involving a change in the structure of the native chromosome. Such changes may involve several different classes of events, like deletions, duplications, inversions, and translocations. Usually, these events are caused by a breakage in the DNA double helices at two different locations, followed by a rejoining of the broken ends to produce a new chromosomal arrangement of genes, different from the gene order of the chromosomes before they were broken. Structural chromosomal abnormalities are estimated to occur in around 0.5% of newborn infants.

The following outline is provided as an overview of and topical guide to genetics:

The 2000s witnessed an explosion of genome sequencing and mapping in evolutionarily diverse species. While full genome sequencing of mammals is rapidly progressing, the ability to assemble and align orthologous whole chromosomal regions from more than a few species is not yet possible. The intense focus on the building of comparative maps for domestic, laboratory and agricultural (cattle) animals has traditionally been used to understand the underlying basis of disease-related and healthy phenotypes.

<span class="mw-page-title-main">Microdeletion syndrome</span> Syndrome caused by chromosomal deletion

A microdeletion syndrome is a syndrome caused by a chromosomal deletion smaller than 5 million base pairs spanning several genes that is too small to be detected by conventional cytogenetic methods or high resolution karyotyping. Detection is done by fluorescence in situ hybridization (FISH). Larger chromosomal deletion syndromes are detectable using karyotyping techniques.

References

  1. ↑ "Biography—Henry H.Q. Heng". Cancer and Metastasis Reviews. 32 (3–4): 321. 2013. doi: 10.1007/s10555-013-9430-z . S2CID   17156539.
  2. ↑ "Henry H.Q. Heng, PhD". genetics.wayne.edu. Retrieved 2022-06-15.
  3. ↑ Henry H.Q. Heng. "Henry H.Q. Heng, PhD". genetics.wayne.edu. Retrieved 2022-06-15.
  4. ↑ "Wayne State Board of Governors' award honors Henry Heng's 'Genome Chaos' book". today.wayne.edu. Retrieved 2022-06-15.
  5. ↑ "Molecular Cytogenetics welcomes new co-Editor-in-Chief". 12 June 2012.
  6. ↑ Henry H.Q. Heng (2006-05-10). "Stochastic cancer progression driven by non-clonal chromosome aberrations". Journal of Cellular Physiology. 208 (2): 461–472. doi:10.1002/jcp.20685. PMID   16688757. S2CID   33441988 . Retrieved 2022-06-22.
  7. ↑ Heng HH (2009-05-31). "The genome-centric concept: resynthesis of evolutionary theory". BioEssays. 31 (5): 528–537. doi:10.1002/bies.200800182. PMID   19334004. S2CID   1336952.
  8. ↑ Julie Heng (2021-12-31). "Genome Chaos, Information Creation, and Cancer Emergence: Searching for New Frameworks on the 50th Anniversary of the "War on Cancer"". Genes. 13 (1): 101. doi: 10.3390/genes13010101 . PMC   8774498 . PMID   35052441.
  9. ↑ James Shapiro (2021-04-27). "What can evolutionary biology learn from cancer biology?". Progress in Biophysics and Molecular Biology. 165: 19–28. doi:10.1016/j.pbiomolbio.2021.03.005. PMID   33930405. S2CID   233471570 . Retrieved 2022-06-22.
  10. ↑ Kezhong Zhang (2020-06-23). "Genome chaos: Redefying genetics, evolution, and environmental factors in medicine" . Retrieved 2022-06-23.
  11. ↑ Christine J. Ye (2019-11-01). "What Is Karyotype Coding and Why Is Genomic Topology Important for Cancer and Evolution?". Frontiers in Genetics. 10: 1082. doi: 10.3389/fgene.2019.01082 . PMC   6838208 . PMID   31737054.
  12. ↑ Heng HH (2009-05-31). "The genome-centric concept: resynthesis of evolutionary theory". BioEssays. 31 (5): 528–537. doi:10.1002/bies.200800182. PMID   19334004. S2CID   1336952.
  13. ↑ Christine J. Ye (2019-05-13). "Micronuclei and Genome Chaos: Changing the System Inheritance". Genes. 10 (5): 366. doi: 10.3390/genes10050366 . PMC   6562739 . PMID   31086101.
  14. ↑ Kezhong Zhang (2020-06-23). "Genome chaos: Redefying genetics, evolution, and environmental factors in medicine" . Retrieved 2022-06-23.
  15. ↑ James Shapiro (2020-10-28). "From Genes to Genomes". Inference. 5 (3). Retrieved 2022-06-23.
  16. ↑ Christine J. Ye (2018-05-11). "Understanding aneuploidy in cancer through the lens of system inheritance, fuzzy inheritance and emergence of new genome systems". Molecular Cytogenetics. 11: 31. doi: 10.1186/s13039-018-0376-2 . PMC   5946397 . PMID   29760781.
  17. ↑ Richard A. Stein (2020-06-23). "Deciphering the Cancer Transcriptome" . Retrieved 2022-06-23.
  18. ↑ Root Gorelick (2010-11-20). "Sex Reduces Genetic Variation: A Multidisciplinary Review". Evolution. 65 (4): 1088–1098. doi:10.1111/j.1558-5646.2010.01173.x. PMID   21091466. S2CID   7714974 . Retrieved 2022-06-22.
  19. ↑ "Wayne State Researcher: Sex Reduces Genetic Variation". 2011-07-06. Retrieved 2022-06-23.
  20. ↑ Rafe Furst (2021-09-03). "The Importance of Henry H. Heng's Genome Architecture Theory". Progress in Biophysics and Molecular Biology. 165: 153–156. doi:10.1016/j.pbiomolbio.2021.08.009. PMID   34481833. S2CID   237423035 . Retrieved 2022-06-22.
  21. ↑ Perry Marshall (2022-05-11). "Genome Architecture Theory shakes up cancer research" . Retrieved 2022-06-22.
  22. ↑ Heng, Henry, and Perry Marshall. “Genome Chaos: Henry Heng Delivers Where Charles Darwin Fell Short.” Evolution 2.0, 26 Nov. 2021, evo2.org.
  23. ↑ Heng HHQ, Squire J, Tsui LC. High-resolution mapping of mammalian genes by in situ hybridization to free chromatin. Proc. Nati. Acad. Sci. USA 1992
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