Evolution and Disease: Exploring the effects of Pathogenesis as a factor driving Natural Selection

Author: Lauren Feist

Affiliation: SUNY Stony Brook University

Publication Year: 2023 (Revised edition)

Title: Pathogens, Evolution, and the Role of Viral Pathogens: Insights into Genetic Variation, Disease Processes, and Evolutionary Change

Abstract:

Pathogens, including viruses, play a significant role in shaping genetic composition and driving evolutionary processes within populations. Through various mechanisms, pathogens introduce genetic mutations into host genomes, leading to new genomic and epigenetic effects. These mutations can contribute to natural selection by conferring advantages or disadvantages in survival and reproduction. The study of pathogenesis and evolution requires collaboration among different scientific disciplines, such as genetics, virology, biology, and chemistry.

By analyzing the genomic composition of infective agents, researchers gain insights into the relationships between pathogens and hosts, as well as the impact of these interactions on evolutionary change. Understanding how pathogens influence genetic variation, frequencies, and mutations provides valuable information about disease processes and the conservation of specific traits. The field of proteogenomics, which combines proteomics and genomics, allows for the exploration of protein structure, function, and expression in relation to genetic variations.

Sequencing entire genomes has revolutionized genetics, providing valuable insights into gene structure and function. Proteomic techniques and the study of post-translational modifications offer new avenues to explore the functions of proteins and their interactions with the genome and epigenome. Mapping protein form and function contributes to a better understanding of disease processes and the development of disease prevention and treatment strategies.
The evolution of pathogens, including antibiotic and disease resistance, is an important area of study within evolutionary development. Pathogens exert selection pressures on populations, leading to the survival and reproduction of resistant variants. Understanding the mechanisms and implications of antibiotic resistance is crucial for developing effective strategies to combat evolving pathogens.

The Borna virus serves as an illustrative example of an endogenous non-retroviral RNA virus. It replicates within human hosts, infiltrating the cell nucleus and transmitting through germ cells. The viral information is distributed within the genomic structure of subsequent generations, influencing gene expression through various mechanisms. The integration of viral genetic material into the host genome raises questions about its potential epigenetic effects and its role in human behavior and mental illnesses.

Further exploration of the human genome and mammal genomes reveals a greater viral component than previously recognized, indicating the existence of fossil viruses with implications for disease understanding and treatment. Viral pathogens, as non-living vectors, uniquely influence their own evolutionary trajectory by invading host organisms. The study of viral pathogens expands our understanding of evolutionary change and selection in living organisms.
Viral evolution can occur within host cells as well as through transmission between different host species, emphasizing the importance of tracking and projecting the evolution of pathogens for effective interventions. Integrating knowledge of viral integration, tumorigenesis, and core transcriptional features associated with neoplastic transformations provides insights into selection pressures, mutagenic changes, and mortalities in global populations. Understanding these mechanisms is crucial for the development of efficient disease management and prevention strategies.

The study of pathogenic populations and their role in evolution provides valuable insights into disease processes, genetic variation, and natural selection. By exploring genomic composition, mutations, and protein functions, researchers unravel the complex relationship between pathogens, hosts, and evolutionary change. This interdisciplinary field of research enhances our understanding of disease prevention, treatment strategies, and the broader implications of evolution in medical sciences.

Overall, this interdisciplinary research field, ( “Evo-Devo Pathogenetics”) contributes to our understanding of disease processes, genetic variation, and natural selection. The exploration of pathogenic populations and their role in evolution has far-reaching implications for disease prevention, treatment strategies, and the broader understanding of evolution in the medical sciences.

Keywords: pathogenesis, evolution, genes, pathogens, genetic variation, proteogenomics, antibiotic resistance.


Here is an expanded section with additional information and a chart highlighting the genes that are potentially involved in the processes described:

Pathogens, including viruses, play a significant role in shaping the genetic composition of populations and driving evolutionary processes. They introduce genetic mutations through various mechanisms, such as integrating their genetic material into the host genome, leading to new genomic and epigenetic effects. These mutations can contribute to natural selection by conferring advantages or disadvantages in survival and reproduction.

The study of pathogenesis and evolution requires collaboration among different scientific disciplines, including genetics, virology, biology, and chemistry. By analyzing the genomic composition of infective agents, researchers can gain insights into the relationships between pathogens and their hosts, as well as the impact of these interactions on evolutionary change. Understanding how pathogens influence genetic variation, frequencies, and mutations provides valuable information about disease processes and the conservation of specific traits.

Mutations, which can arise spontaneously or be caused by mutagenic factors, are essential for evolution by natural selection. They contribute to the diversity and polymorphic variances within populations and can be inherited through reproduction. Studying mutations and their effects on gene function and protein production deepens our understanding of the genetic basis of diseases and complex traits. The field of proteogenomics, which combines proteomics and genomics, allows for the exploration of protein structure, function, and expression in relation to genetic variations.

Sequencing entire genomes has been a groundbreaking advancement in genetics, providing insights into the structure and function of genes. Proteomic techniques and the study of post-translational modifications offer new avenues to explore the functions of proteins and their interactions with the genome and epigenome. By mapping the form and function of proteins, researchers can gain a better understanding of disease processes and potentially develop strategies for disease prevention and treatment.

The evolution of pathogens, including antibiotic and disease resistance, is an important area of study within the context of evolutionary development. Pathogens exert selection pressures on populations, leading to the survival and reproduction of resistant variants. Understanding the mechanisms and implications of antibiotic resistance is crucial for developing effective strategies to combat evolving pathogens.

The study of pathogenic populations and their role in evolution provides valuable insights into disease processes, genetic variation, and natural selection. By exploring the genomic composition, mutations, and protein functions, researchers can unravel the complex relationship between pathogens, hosts, and evolutionary change. This interdisciplinary field of research has the potential to enhance our understanding of disease prevention, treatment strategies, and the broader implications of evolution in the medical sciences.

Now, let’s chart some of the genes that are potentially involved in these processes:

Gene Name Function
p53 Tumor suppressor gene, regulates cell cycle and apoptosis
E6 Oncogenic protein of Human Papillomavirus
E7 Oncogenic protein of Human Papillomavirus
LINE Long Interspersed Repetitive Elements
URR Upstream Regulatory Region of HPV
H1N1 Influenza virus strain
HIV Human Immunodeficiency Virus
Various oncogenes and tumor suppressor genes Involved in neoplastic transformation and progression

Please note that this is not an exhaustive list, and there are numerous other genes and genetic elements that play significant roles in pathogenesis, evolution, and disease processes. The specific genes involved can vary depending on the pathogen and the host species under study.

 



Pathogens, including viruses, play a significant role in shaping the genetic composition of populations and driving evolutionary processes. Pathogens can introduce genetic mutations through various mechanisms, such as integrating their genetic material into the host genome, leading to new genomic and epigenetic effects. These mutations, in turn, can contribute to natural selection by conferring advantages or disadvantages in survival and reproduction.
The study of pathogenesis and evolution requires collaboration among different scientific disciplines, including genetics, virology, biology, and chemistry. By analyzing the genomic composition of infective agents, researchers can gain insights into the relationships between pathogens and their hosts, as well as the impact of these interactions on evolutionary change. Understanding how pathogens influence genetic variation, frequencies, and mutations can provide valuable information about disease processes and the conservation of specific traits.

Mutations, which can arise spontaneously or be caused by mutagenic factors, are essential for evolution by natural selection. Mutations can be inherited through reproduction, and they contribute to the diversity and polymorphic variances within populations. By studying mutations and their effects on gene function and protein production, researchers can gain a deeper understanding of the genetic basis of diseases and complex traits. The field of proteogenomics, which combines proteomics and genomics, allows for the exploration of protein structure, function, and expression in relation to genetic variations.

Sequencing entire genomes has been a groundbreaking advancement in genetics and has provided valuable insights into the structure and function of genes. The ongoing development of proteomic techniques and the study of post-translational modifications offer new avenues to explore the functions of proteins and their interactions with the genome and epigenome. By mapping the form and function of proteins, researchers can gain a better understanding of disease processes and potentially develop strategies for disease prevention and treatment.

The evolution of pathogens, including antibiotic and disease resistance, is an important area of study within the context of evolutionary development. Pathogens can exert selection pressures on populations, leading to the survival and reproduction of resistant variants. This phenomenon can be likened to predators and prey, where antibiotics act as the predator, killing some bacteria while allowing resistant variants to survive and proliferate. Understanding the mechanisms and implications of antibiotic resistance is crucial for developing effective strategies to combat evolving pathogens.

The study of pathogenic populations and their role in evolution provides valuable insights into disease processes, genetic variation, and natural selection. By exploring the genomic composition, mutations, and protein functions, researchers can unravel the complex relationship between pathogens, hosts, and evolutionary change. This interdisciplinary field of research has the potential to enhance our understanding of disease prevention, treatment strategies, and the broader implications of evolution in the medical sciences.

The Borna virus serves as an illustrative example of an endogenous non-retroviral RNA virus. Endogenous viruses originate within the tissues, organisms, or cells themselves and can impact the genetic makeup and functioning of the host. Empirical evidence suggests that the Borna virus is capable of replicating within human hosts by infiltrating the cell nucleus and subsequently transmitting through germ cells such as spermatozoa and oocytes. During gametogenesis, when germ cells from progenitor species merge, the viral information is often distributed within the genomic structure, specifically the chromosomes, of subsequent generations. The offspring’s genome becomes influenced by the provirus, which is the latent or concealed derivative of the Borna virus that has successfully integrated into the genomic structure. This integration occurs in regions where reverse transcriptase activity takes place or is encoded in Long Interspersed Repetitive Elements (LINE) or Long Interspersed Nuclear Elements (LINE).

It is plausible to speculate that this process could potentially trigger an epigenetic effect within certain loci of gene expression, leading to various outcomes such as epigenetic silencing, linkage, epistasis, null effects, or deletion mutations. In addition to these conjectures, the Borna virus has been identified as “replacing” the function of reverse transcriptase activity along LINE-1, where DNA copies of RNA are synthesized and inserted into the genome. Over generations, the viral DNA undergoes mutations, eventually losing its ability to mutate and becoming disabled.

Considering the aforementioned, one might question whether these viral remnants act as mediators of susceptibility to other viruses through overlapping protein sequences in a domain. In fact, an inverse relationship of this nature appears conceivable when examining the research of Dr. Keizo Tomonaga, a virologist at Osaka University, who fortuitously discovered that four segments of human DNA share clear ancestry with the Borna virus. Dr. Tomonaga’s theory proposes that the Borna virus did not invade mammalian genomes but rather that the genomes “kidnapped” the viruses, suggesting a synergistic relationship between human and viral genes. He suggests that LINEs, which have the ability to create copies of themselves, captured genes from the Borna virus and reintegrated them back into the genome. If this hypothesis holds true, it is possible that LINEs have also acquired genes from other viruses and utilized genetic material from those viruses in advantageous ways.

In his article “Hunting Fossil Viruses in Human DNA” (2010), Carl Zimmer mentions that the neurotropic Borna virus is just one of many viruses that infect mammals and birds. It is worth noting that birds, insects, and humans share a unique relationship, as vectors like mosquitoes are known to transmit viruses across species boundaries. Consequently, the presence of the Borna virus in various species is not surprising. Zimmer further explains that some species infected with this virus exhibit no symptoms, thereby rendering the effects of the infectious agent largely enigmatic, with specific exceptions. For instance, horses have been observed to display behavioral effects, such as wild fits that may lead to self-inflicted fatal injuries or starvation. Researchers have postulated a correlation between the Borna virus and human behaviors indicative of disorders such as schizophrenia. However, when considering the recent identification of protozoa affecting human behaviors and their role as pathogens or parasites underlying disorders like schizophrenia, we may gain further insight into the influence of pathogenesis on behaviors. The idea that pathogenesis can contribute to mental illness or influence behavior remains a topic of controversy, analogous to the initial debates surrounding the proposition of humans descending from primates. Anticipating a potential controversy over the notion that humans have limited control over their behaviors, the identification of pathogens responsible for behavioral influences could pave the way for targeted interventions and potentially lead to cures for various mental illnesses.
An alarming hypothesis, should it be considered conclusive, suggests that around 40 million years ago, the Borna virus infected our primate-like ancestors. Viruses are estimated to be present in approximately 8% of the genome in every individual on Earth, primarily in the form of endogenous non-retroviral RNA virus elements in mammalian genomes. To put this percentage into perspective, it is seven times greater than the DNA content of all the 20,000 protein-coding genes in the human genome. The completion of the human genome sequencing in 2001 revealed that several segments of human genes bear resemblance to retroviral genes. While scientists have identified connections between approximately 100,000 viral elements, mostly originating from retroviral infections, imprinted within the human genome, the discovery of the Borna virus as a component of the human genome represents a novel finding. This suggests that many other viruses may still await discovery within the human genome. Consider the implications of unraveling the form and function associated with these viruses—what other insights could be gained about known or unidentified diseases and their potential treatments?

The Borna virus is not the sole instance of fossil viruses revealed through gene mapping and referencing databases containing human genome sequences. Researchers are expanding their scope beyond the human genome and capitalizing on the growing number of mammal genomes available in online databases to elucidate the evolutionary history of viruses dating back millions of years. Collectively, these investigations provide compelling evidence that humans and other species have a greater viral component than previously recognized.
Of all the various pathogens I will discuss, viral pathogens, or “pathogenes” as I prefer to refer to them, hold particular significance. Unlike other pathogenic agents such as prokaryotes, archaea, and protozoa, viruses are technical, non-living vectors. Viruses uniquely possess genetic material that is not alive per se, requiring invasion of host organisms for survival and replication, thereby influencing their own evolutionary trajectory. The optimal conditions for viral evolution often arise when the host organism is not exploited to the point of death, ensuring the virus’s survival and reproduction in greater numbers. This concept theoretically applies to viruses, as it serves as the foundation for evolution through natural selection in living organisms. However, it is also plausible that certain viral pathogens may evolve by exploiting a host to the point of fatality while concurrently being transmitted to another host, facilitating evolutionary changes in both the host and viral populations. Viruses may evolve as they multiply within cells and reproduce. Is there a limited advantage, yet an advantage nonetheless, for viral pathogens gained by integrating into the host genome either during active infection or afterward as proviruses that are inherited by subsequent generations, thereby preventing their complete obsolescence? In my view, the answer is likely affirmative. This driving force of evolution is not limited to humans and animals but may extend to interactions between prokaryotes, archaea, and protozoa—what I term the “pathogen-to-pathogen route.” For example, eubacteria may be exploited by a viral population, presenting a symbiotic advantage in both populations. When examining the relationships between eukaryotes, prokaryotes, and archaea, we should explore a pathogenic phylogeny encompassing all domains and subsequent taxonomies.
Oncoviruses, which promote tumorigenesis in humans and animals, represent another extensively researched topic that expands our understanding of how viral pathogens can drive evolutionary change or at least fulfill the criteria necessary for selection to occur.

Interfering with the action of p53 allows a virus-infected cell to progress into a different stage of the cell cycle, promoting replication of the virus genome. Forcing the cell into the S phase of the cell cycle can potentially lead to cellular transformation (Scheffner et al., 1990).

According to a study conducted by the National Cancer Institute, HPV 16 is the most common type, accounting for 61% of cervical cancers, followed by HPV 18 at 9%. Types 33, 45, 58, and 59 were each found in one specimen. Analysis of the genomic sequences of HPV 16-positive isolates revealed distinct patterns of stability and variability in the upstream regulatory region (URR) and the E6 and E7 genes. Mutations were observed in 5% of the URR, including a large deletion in one isolate and various point mutations affecting regulatory sites. More sequence variations were found in the E6 gene compared to the E7 gene. Mutations in these genes, which encode the oncogenic proteins essential for malignant transformation, may impact the oncogenicity of the virus by altering amino acid sequences or transcription factor binding sites (Human Papillomaviruses and Cancer, National Cancer Institute, 2008; Int. J. Cancer 86:695-701, 2000).

Furthermore, it has been observed that viral evolution can occur not only within host cells but also through transmission between different host species. Examples include the H1N1 influenza virus, which originated in swine populations and crossed the species barrier to infect humans, as well as avian influenza viruses undergoing multi-species crossing-over.

In terms of gene expression and profiling, a large-scale meta-analysis of cancer microarray data revealed common transcriptional profiles associated with neoplastic transformation and progression. This analysis examined 40 published cancer microarray datasets, encompassing over 3,700 cancer samples and 38 million gene expression measurements. The findings indicated a common transcriptional profile in various forms of undifferentiated cancers, suggesting core transcriptional features associated with neoplastic transformations and the perpetuation of cancer development (source: Large-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progression).

These findings highlight the significance of viral integration within the human genome and its role in driving evolutionary changes, with tumorigenesis being one measurable outcome. Understanding these mechanisms is crucial in medical science, as it provides insights into selection pressures, mutagenic changes, and mortalities in global populations. By comprehending the evolutionary aspects, research can be directed towards developing effective treatments and prevention strategies. Targeting the most virulent strains of pathogens while minimizing harm to the host appears to be a promising approach for disease management and prevention of resistance. However, in the case of HIV, all variants of the virus exploit the host in harmful ways, posing challenges for this approach. Thus, closely tracking and projecting the evolution of pathogens is crucial for the development of efficient interventions.


Citations

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References

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The Evolution of the Brain: Intro to The Prefrontal Cortex and Mirror Neurons

What makes humans different from other animals in terms of our ability to communicate and cooperate extensively and to use our imaginations to simulate reality in order to understand ourselves and others?

The Evolution of the Human Mind and Brain: Mirror Neurons

I would like to begin my discussion of the evolution of the human brain by focusing on the most marked distinction between humans and other animals- the evolutionary development of the cerebrum. Also known as the prosencephalon, the forebrain, or the pre-frontal cortex.

The forbrain is compossed of the telencephalon or the anterial cerebral hemispheres and the diencephalon which is the hypothalmus and the thalamus. The developmental forms and variation of neural structures in the highly plastic forebrain, implicate function, where human behaviors are concerned.

Consideration of human behaviors and the role of agency leads to theories about the human mind which will be discussed toward the end of this essay.

The article, MIRROR NEURONS and imitation learning as the driving force behind “the great leap forward” in human evolution by V.S. Ramachandran highlights the fact that the hominid brain reached it’s present size almost 250,000 years ago. Note, that is around the time that “Mitochondrial Eve” our most common female ancestor would have lived. {Could it be plausible that mitochondrial DNA integration (I.e. The endosymbiotic hypothesis) has a driving factor in human brain evolution?}

Throughout the history of hominid evolution, going back to over four million years ago, there is evidence that the pre-frontal cortex has increased in cognitive capacity, sixfold. {This sixfold increase indicates exponential growth. Did this growth stop or will it increase exponentially through genetic integration by means of pathogenesis? (See, Pathogenesis as a Driving Force in Natural Selection. 2010. Feist, L.) Further, will human “junk DNA” or non-coding DNA be activated further by genetic integration therefore catalyzing cognitive expansion as a product of human brain evolution? I suggest it so!

While Ramachandran suggests that the human brain may have also reached its present intellectual capacity about 250,000 years ago, I am not in complete agreement, clearly. It seems plausible to think this is possible on one hand, because in biology, form illicits function. This is a central dogma of modern biology as we understand it. So, if the brain was a particular size it may have been comensurate to potential for higher abilities, however, evidence suggests that the emergence of language, and other behavioral specializations may not have appeared to much later during the “great leap foward” which is defined by the emergence of abilities such as tool use and building, fire making, artisitc and creative representations and language. In fact, the brain capacity of our ancestors evidenced by the fossil record cranial morphologies, is not distinguished by brain size. The question is how these latent abilities, in terms of behavior arrose especially if they remained dormant for epochs of time? Were these abilities dormant? The question addresses a problem in terms of selection as expressed abilities can only be selected and not latent. He calls this “Wallace’s problem” as it was first proposed by Alfred Wallace. I emphasize this problem as I would like to attempt to address it from my perspective based on what I have learned insofar on the topic of human neurobiological development from an evolutionary standpoint.

I think it is important to consider that selection pressures must have favored the expansion of the pre-frontal cortex and therefore, we have to understand some of the anatomical features of this organ structure, which we covered a bit. It is unlikely that a trait would come to be predominant in a population if it had not posed an advantage to survival but just as it is difficult to imagine the adaptive mechanisms or better yet the factors that allowed for the move from obligate locomotion to bipedal locomotion, it is difficult to determine how the brain expanded from the hind-brain and mid-brain structures to develop inline with a forebrain. We know that all of these structures are linked together by neural networks, and this is often referred to as the triune brain or less formally, the reptilian brain. However, when we talk about the devlopment of the pre-frontal cortex, we are talking about the development of a structure, that is largely defined by a general form, a form that is observably similar in size in all homo sapiens, dating back to 250,000 years ago. What complicates the investigation of the hypothesis by Wallace is the problem of differentiation in individual variants of a population which are based on a variety of factors, that not only include hereditary factors, but broad environmental factors; This is to say that variations for characteristic features of the pre-frontal cortex as well as other elements of other brain structures, play a role in diversity which must link to functional abilities in ways yet to be understood.

The unified aspects of neurobiological development are likey the features that allow us to relate to others when we continue to hold that form indicates function. This is why I think the emphasis on similarities between structures should be looked at when we consider the evolution of the brain rather then the aforementioned differences. To explore the origin of the pre-frontal cortex is like exploring the origin of man; It is a complicated, evidence-limited, speculative and highly theoretical topic of consideration. In reiteration, the prefrontal cortex appears in its present size some 250,000 years ago, while the origin of man can be traced back to a primate lineage. This lineage appears almost 5 million years ago, while beyond that, we don’t know exactly how or from where the first life sprung up. Many theories point to the increased complexity of micro-organism in the emergence of early life forms. As populations reproduce, they often become more complex, but how would this explain the cambrian explosion? Why did so many complex life forms arrise during this period? To consider the magnitude of this question is to consider the magnitude of how all homo sapiens appeared to have developed a pre-frontal cortex. I think it is acceptable to at least consider that micro-organism, and theories such as the endosymbiotic hypothesis play a role in not only the development of biological structures, but the emergence of some entirely. The endosymbiotic theory proportes that mitochondrial DNA, as a structural tangent of our human genome, emerged as a result of genetic integration between prokayotic eubacterial cells and eukaryotic cells roughly 200,000 years ago (a time-line close to the emergence of the present day size of the pre-frontal cortex). This integration is based in the idea that synergenrnisitc relationships exist between cells and genetic information. I sometimes think that synergenisic reactions may have taken place between the organic molecules composing earlier life-forms, in an “explosion” similar to the irreversible fusion reactions observed of the synergy between chemicals in the setting off of an atom bomb. In this very imaginative consideration, if we could just for a moment think that this idea concerning synergy, is possible, we might wonder if such a process could have not only catalyzed the emergence of the pre-frontal cortex as a structure but also the ongoing specializations of sub-structures and functional elements within it, such as motor neurons. This is my best hypothesis as to why the human pre-frontal cortex may have emerged and also why the functial abilities it enables were manifest as “latent.” If it is not clear yet, my belief is that the human brain is host to many “latent” abilities in the present, which will not yet be actualized. I always mention that form indicates function but know in that, that form must come before function. I am also suggesting that evolution drives not only gradual changes in the human body over sucessive filial generations but that “catastropic” changes also take place less frequently, leading to a sort of puncutated equlilibrium in human development. Punctuation could explain the emergence of the prefrontal cortex. Where punctuation could be facilited by synergisitc “tipping points” and the accumulation or aquisition of certain sub-atomic or atomic properties leads to an “explosion” of presently immesruable results, in terms of origin. I further suggest that such a synergy between sub-atomic or even atomic biochemical molecules might occur at a sub-genomic level where the effects of such a process are apart from the role of genes as implicated in terms of function. I understand that this is a radical proposition but if you think about it, the double helical structure of DNA is constant in form but it is the alleles that undergo change. Perhaps it is important to look at the molecules that determine the double helical structure of DNA, which are mainly carboxal functional groupings and poly-peptide bonds, and determine if there are governed by constant “laws” that are synergistic between atomic molecules such as these, that allow for the maintainance of permanent strucutures, or structures that appear as uniform in all of the homo sapien populations. To this end, let’s speculate that the adaption or integration of certain molecular or even sub-molecular elements into the human genome may influence inversion changes that interrupt equilibrium as result of “accumulation” where enough of some “ingredient” is then present to catalyze a significant or punctuated change? (See, the Traveling Salesman Problem)

More simply, I suspect that both natural selection and sexual selection played an integral role in the evolution of the pre-frontal cortex and that the structure itself may have in fact expanded to its present volume or mass (as opposed to size) some 250,000 years ago, but that it became more specialized gradually, which ultimately led to the emergence of higher thought and behavioral processes. It may be that single specialization arrose and was selected for the advantages they gave in survival, at different times and that as each specialization was selected and “accumulated” the internal structures of the pre-frontal cortex began to correspond to another through neural pathways. (I.e. the mesocorticolimbic pathway that connects the mesenchephelon to the pre-frontal cortex. If we look at single nucleotides, we see that they combine to form triplets or codons where the sequences codes for specific proteins. Mutations in single nucleotides may create different protein products. (See, the Three Forms of Mutation) This is systematically relevant because proteins illicit the functional abilities of the cells. A specialization of for instance, motor neurons, may have been the result of polymorphisms represented by mutations in single nucleotides. A resulting specialization that posed some survival advantage, even though it may have arrose due to mutation, may have still been selected! We have the evidence of such genomic changes, across species. Advantages may still in fact be latent in that the advatage comes with changes in environmental factors. The environment of early homo sapiens may have changed as populations expanded in terms of numbers and not genetic variation alone. A population may have expanded in terms of numbers when for instance, the protein, syncitin, was integrated within the human genome and enabled an increase in the number of vital births OR when climate changes allowed more vegetative growth in a region, etc. When a population expanded, hominid-to-hominid interactions may have increased. Certainly when these interactions included interbreeding, diversity would have been increased much in the way that pathogens increase diversity. The disadvantages of an expanding population would be increased competition, both interspecific and intraspecific, which would also drive geographical expansions. Why? Well because there would be uninhabited lands with proficient resources to expand into. However, advantages of cohabitation and living in groups would include the coordination of activities centered on aquiring food, building shelters, and defense against other groups seeking to compete for resources. Survival advantages that came with expanding populations would likely outweigh disadvantages. So, how does this all relate to the evolutionary development of the pre-frontal cortex? It seems as though interactions between homo sapiens illicit emotional responses that forge pathways to higher cognition! Greater numbers in a population means there would be greater exposure or oppertunity to interact, if not a necessity to communicate. Initially, communication must have been based upon the neurobiological functions of other parts of the brain, even prior to the emergence of homo sapiens. Thinking about it, it is possible that those who could communicate more efficiently could also solve many problems of survival. Think about our modern sociocultural hierarchies across societies- it is the strong communicators that are selected as leaders. Problem solvers are desirable mates and would likely have higher reproductive values and rates of succession because the survival advantages posed by communicative abilities would be selected for in terms of sexual selection, resulting in natural selection and finally, evolutionary change. There must have been some mechanism for attracting a mate beyond the display of secondary sex characterisitcs. Emotional signalling via facial representations may have been a mechanism by where feelings were the modality of communication. If this was occurring in primitive human forms, it would certainly be evidenced today, as it is. The center in the brain for emotions is the Limbic System. It evolved prior to the pre-frontal cortex, but it is presently intertwined with the functions of the forbrain.

Emotional responses originating in the limbic system allow humans advantages such as the ability to perceive and respond to danger- where danger illicits fear, then a fight, flight or freeze “deer in headlights” response. The inner feeling of fear can be exhibited as an outward expression of fear as reflected in facial gestures, which are controlled by the nervous systems, creating the tensor and flexor coordinating motions of our 43 facial muscles. Gesturing or “body-laguage” is perceivable to an observer and can interestingly illicit a similar response of fight-or-flight in both, the individual experiencing danger and the individual obsering another in danger. This communicative ability arrose prior to the development of language and may have been a basis for cooperation, where individuals that experienced the same danger, could respond in line with the other based on empathetic abilities. I beleive that a primative gestural communication system was in place prior to the establishment of language and that gestural communication provided a scaffolding for such emergence of vocal language. But here’s another question for the books- if 90% of communication is body language, have we preserved our most primitive form of communication? We likely have many more intrinsic responses then we can understand. This may relates to the subconscious, which is said to be 30,000 times more powerful then the conscious mind. We know that instinct is governed much by the mid-brain emotional centers but what if, we revisit the hypothesis that the activation of “junk DNA” is occurring by way of genetic integration- will the subconscious expand as well? As scientists, we need to seek out this evidence. How could we not expect the exponential growth to continue? Our understanding of the brain has spread from Galen, the physicians understanding of the structure as a glandular organ, to the pseudoscientific ideas of phrenology, to the pseudoscientific ideas of the present westernized idea that the human race is ascending into higher thinking! Not all imagination and creativity is lost on the pseudoscientific postulates that are created to explain neurological phenomena. But do you want more evidence? Furthering my research, I find that the neurological phenomena of synesthesia -which is the crossing over of the primary 5 senses to create secondary and tertiary senses- that is, 6th and 7th senses and so on. It is as if the primary colors of the primitive brain have become a color wheel of specialized sensory functions in some human variants that manifest this disposition. Laterally, I suspect the genetic trend and emergence of synesthesia will become more common place.

One of the most obvious of human abilities in terms of the difference between humans and other animals ability to communicate and cooperate extensively with others, is verbal communication. I do not think that the human ability to communicate verbally necessarily surpasses the need for non-verbal communication skills but that often, the two areas overlap, to create very complex communicative strategies and processes. Sometimes, we see a conflict over the benefits of a selected trait based on advantages it offers in natural selection versus sexual selection. For instance, a trait such as fair skin may appear in a population more frequently because lighter skin indicates health more clearly then darker skin, however, fair skinned individuals may be more prone to conditions such as melanoma when exposed to ultraviolet light more frequently then darker pigmented skin containing more melanin. We still see fair skin characterisitcs in human populations because the sexual preference for this trait trumps the process of natural selction in diminishing the frequency of the trait. We may consider why and how other abilities evolved by looking at factors for both sexual selection and natural selection. In the case of the human ability to communicate and cooperate, it seems that dual advantages rather then opposing advantages, exist in both processes of selection- a conserving dichotomy. This is probably why we see the relationship between self actualization as parallel and closely correlative to the role of agency and shared represenations. New evidence suggests that how these representations play out, depends on the functional ability of mirror neurons, also called empathy neurons, in neurocircutry and some related structures in the brain.

The initial discovery of mirror neurons in the frontal lobes or ventral promoter regions in monkeys is attributed to Giaccamo Rizzollati. As evolution theory has indicated humans to be decendent from ape-like ancestors, this discovery sparked the search for mirror neurons and their function within the human brain. It has been suggested that humans have an ability to read into the minds of others and thereby approximate the behavioral processes of others in order to respond, and even to outsmart others. As much as this notions suggests that the ability to relate to others through simulation could be used as a competitive advantage, it stands to account for predominate benefits in cooperation.

Mirror neurons allow for action recognition where perceptive responses are simulated in the brain of an observer as a process reflective of that which occurs in the brain of the individual who is actually doing the action. This ability for action recognition has been tied to the evolutionary development of neurolinguistic abilities in humans. In fact, Arbib and Rizzolatti (1997) demonstrate how mirror neurons may illuminate an evolutionary path between manual skills to language aquisition. Once again, evidence, that this aquisition is one example of a skill that may be modulated by the signinalling of mirror neurons in the brain, that has given up an evolutionary advantage in communication and cooperation.

Mirror neurons have enabled the evolution of consciousness and empathy. For example, nociception involves the process of perceiving pain when one has been injured. It has been demonstrated in functinal magnetic resonance imaging (fMRI) studies that an observer of an individual experiencing pain is potentiated to respond emapthetically through nociceptive responses of their own and this too is possibly due to modulation of signals involving mirror neurons.

The human population in a general sense is quite different from other animal populations, especially when it comes to neuro-specializations that aid in the constructs of social functions. However, there have been observations of some similar social dynamics that are observed in human populations, in primate populations. (See, Bonobo Monkeys) As primates are our closest living ancestors, they serve as an important animal model for some behaviors. One of the defining attributes of sociocultural dynamics in human and some primate populations is the necessity and(or) benefit of interdependence. Humans are born into the world completely dependent on others. The initial primary social setting is the family unit. In time, a human progresses through several developmental stages. Early childhood, and the toddler years marks a developmental stage where the goal is to begin to seek autonomy while the behavior is centered on self-actualization; A toddler begins to view themself as seperate from their parental counterparts. Piaget and other developmental Psychologists beleive that the early childhood developmental process is central to cognitive development where pathways between the mid-brain and pre-frontal cortex are forged especially in response to the social dynamics of the environment. Social-cognitive development in relationship to age-task criteria is sometimes measured in accordance with the Piaget – Parten scale. While we may have scales to measure cognitive-development, they do not give us the whole picture but rather a statistical measure of perceptive or subjective behaviors in accordance to the limiting factors of age-appropriate expectations. In adolecesnce, there comes a second pursuit of autonomy marked by a movement from the familial setting as primary to the familal setting as secondary to the social environment. Adolecent populations are interesting because there are marked accounts of socially enigmatic behaviors that indicate patterns of integreation based upon emulation or immitation, to some notable degree. The autonomous self in adolecense seeks identity within a social group often bearing certain distinctions. Also, the defining characterisitcs of social groups may be period-specific. Throughout all stages of autonomous development, mastery is a general goal, whether it be mastery over grooming oneself in early childhood or driving a vehicle in adolecense. In that, the higher goal of mastery by adulthood is to become completely autonomous while facilitating the ability to work interdependently with others based on the perception of self-actualization. The process of introspection may lead to subjective perceptions of others at any stage of development and the function of mirror neurons therein must be to carry out such relational abilities. While the process of social learning has often been measured commesurate to neurobiological cognitive development, the exact mechanism that forges connections, especially social connections, has not always been clear. Theories have extended to explain that the structures of the mid-brain ellicit emotional responses that stimulate potentiation sites in regions of the frontal cortex as a modality for learned associations through a host of neural networks; The process is non-linear as there are neural-networks involved. I believe that the recent discovery of mirror neurons could shed more light on this process in terms of social learning and perhaps be of even greater import to academic learning in groups. If this is the case, we could make an academic and ethical argument for social learning to be preserved in our increasingly technological society that has come to replace real classroom settings with online classrooms. These settings create no true background for meaningful human interactions, which in lieu of this evidence, is vitally important to development.

Social learning is important in the human ability to relate to others but the discovery of mirror neurons indicates that it is actually the emotional ability to relate to others that leads to social learning. Social learning in this way ties into the role of interdependence within groups and carries through a theme of integration. In order to effectively work interdependently with others we need to be able to take account of the behavior of others on some level. Mirror neurons allow us to give account to the behavior of others in a unique way, that may be instinctive as well as concious, where stimulation of simulation in neural activity involves these specialized cells. While historic accounts emphasize such values as reason, logic and morality in consideration of human cooperation, which is synonomous to interdependence as an advantage to human populations in particular-the profound disovery of mirror neurons within the past decade tells us that humans demonstrate reciporicity in unexpected ways. The discovery of mirror neurons has expanded into several perspectives as to how humans understand one another in terms of emotional perception which also explains cognitive responses. In human subjects, a number of functional imaging studies demonstrated the involvement of motor representation during the perception of action performed by others (Hamzei et al. 2003). There seems to be a paradoxical inverse connection between intersubjection and intrasubjection that facilitates empathetic responsiveness between an agent and the object(s) of subjection.

 

Cognitive neuroscience has cited evidence indicating that actions are represented in the central nervous system, and that
representations may be emulated covertly (think subconscious) or overtly in a number of ways where action involves a covert stage, corresponding to its pragmatic representation, which includes its goal, the means to acheive it, and its consequences (Jeannerod, 1999). From this extends the indication that mirror neurons play a role in perceptions through the act of imagination, subjection of oneself and others as well as simulation. For instance, if an individual drinks out of a cup, specific areas of the brain such as the somatosensory system is involved in the process of this action which potentiate the responses to occur, while an individual who observes someone drinking out of a cup, may also experience similar neural activity that they would if they were drinking out of the cup themselves.
This may or may not lead to a responsive action of the observer. In either case, this is the process by where mirror neurons create a modality for learned social behaviors. Could it indicate a role of mirror neurons in memory formation and addiction? (See, Creb protein and cellular memory formation, not to be confused with the Krebs cycle; Memory Formation and Addiction. Feist, L. Developmental Biology. 2010) Performing a movement leaves behind a bidirectional association between the motor patter it was generated by and the sensory effects it produces. Such an association can then be used backwards to retreive a movement by anticipating its effects (Hommel, 2004). This is another integral part of the emotional responsiveness that leads to learned social behaviors. {In human subjects, a number of functional imaging studies demonstrated the involvement of motor representation during the perception of action performed by others (Hamzei et al., 2003).} In support of this idea one study showed images of possible and impossible movements to its participants. During the observation of the movements, areas of the participants brain showed activity that would be similarly observed if the participant were to do the activity themselves. This is because they were imagining or simulating the activity in their mind while observing it. (See, The double Slit Experiment) The exception here is that no activity was oberved when participants viewed movements that were impossible. In another study, participants viewed ballet dancers. The participants who knew how to perform ballet showed more responsiveness to the observed movement then those who had not ever practiced ballet.

The brain in a sense is like a muscle, which is strengthened by observing the action of others which is an assertion supported by vast scientific evidence. Observing the action of others illicits an emotional based response which creates higher cognitive connections. It is known that the frequency of activity of neurons which modulate signals through chemical messengry in the brain create potentiation sites on post-synaptic receptors. This means that each time a neuron sends a signal to a post-synaptic receptor it potentiates a more rapid response to a similar stimulus. This process also indicates the plasticity of the brain and the organs ability to adapt to environmental stimuli. In the case of emotional responses stimulated by the action of mirror neurons, it seems as through the envrionmental stimuli is the observed action of others. In observing the action of others, there may be a memory forged where latency can be demonstrated in the form of imaginative scenarios where the action of mirror neurons extends from real-time, reality based expereinces to creative representations. I mentioned that these creative, fictional representations may also influence empathetic behaviroal responses. For instance, an individual may view a scene in a movie and feel sadness even though the characters and the circumstances are not real. This response may likely be supported by the action of mirror neurons. It is indicated that the ability to imagine may involve mirror neurons in modulation of perception of self and others where additional processes influence social interactions such as the ability to imagine the behavior of others. Perhaps this is why Einstein values imagination and creativity above all else? He intuited its value in the social and higher learning context.

If we want to look at a main tangent of ability relating to the functional role of mirror neuron signaling we can consider imiatation or simulation in it’s own right as a behavior and understand the modality of imitation in the higher cognitive processes and relational abilities within social contexts that are both real and imaginary AND that involve the actualization of perception for ones own and others behaviors as infleuntial over subjective states of awareness linked to domain-general mechanisms and domain-specific representations. Imitation may begin with observing an action that an agent is able to replicate which may illicit a introspecitive and(or) intraspecitive response.

When we begin to think further about the human ability to communicate and cooperate, the idea that these abilities are catalyzed through feelings as opposed to the thought process alone, is unique to the understanding of human behavior. Behavioral representations in humans are complex especially in regard to socially integrated abilities to communicate.

THE EMERGENCE OF LANGUAGE

Unlike many other human traits such as humor, art, dancing or music the survival value of language is obvious — it helps us communicate our thoughts and intentions. But the question of how such an extraordinary ability might have actually evolved has puzzled biologists, psychologists and philosophers at least since the time of Charles Darwin. The problem is that the human vocal apparatus is vastly more sophisticated than that of any ape but without the correspondingly sophisticated language areas in the brain the vocal equipment alone would be useless. So how did these two mechanisms with so many sophisticated interlocking parts evolve in tandem? Following Darwin’s lead I suggest that our vocal equipment and our remarkable ability to modulate voice evolved mainly for producing emotional calls and musical sounds during courtship (“croonin a toon.”). Once that evolved, then the brain — especially the left hemisphere — could evolve language.

Rizzolatti’s discovery can help us solve this age-old puzzle. He recorded from the ventral premotor area of the frontal lobes of monkeys and found that certain cells will fire when a monkey performs a single, highly specific action with its hand: pulling, pushing, tugging, grasping, picking up and putting a peanut in the mouth etc. -different neurons fire in response to different actions.

The sudden explosion of human mental abilities and culture is sometimes called the “big bang.” If the brain reached its full human potential — or at least size — 200,000 years ago why did it remain idle for 150,000 years? Most scholars are convinced that the big bang occurred because of some unknown genetic change in brain structure. However, the changes are at least partly
because of imitation learning and rapid “cultural” transmission of knowledge, promoted by the action of mirror neurons as indisputable evidence toward human behaviors.

Introduction to Topics in Evolution

“Light will be thrown on the origin of man and his history” are the notable words of Charles Darwin in the introduction of The Descent of Man (1871).

Evolution arrose as a controversial topic, initially during the 19th Century. Much of the controversy derived from conflicts between religious or spiritual beleifs in creationism and naturalism and contentions were wagered against the ideas involved in the new theory that undermined those beliefs. Even those who accepted the theory as it applied to all living taxa, refused the idea that humans may have decended from ape-like ancestors.

Thomas Henry Huxley, a collegue and friend of Darwin, adressed the topic of the ancestral origins of man in Man’s Place in Nature (1863) while Darwin developed his ideas about the origin of humans in The Descent of Man (1871), shortly thereafter. He effectively predicted that our human ancestors would be found in Africa.

We should also know that Darwin was heavily influenced by the work of the Geologist, Charles Lyell. During Darwin’s time as a naturalist aboard the HMS Beagle, (when he made many notable observations that would lead to the development of his theory decades later) he kept volumes of Lyell’s, Principles of Geology (1830-1833). These works introduced Darwin to the topic of Uniformitarianism. Lyell’s ideas suggested that geological and biological forces were working the same way. This culminated in an old-earth theory, which suggested that the universe was billions of years old and therefore so was the earth. These theories worked as a framework in support of gradualism.

In time, the theory was accepted by the general population and the previously challenged notion of common descent or that we evolved from ape-like creatures, was thought plausible.

Intially, much of the evidence in support of the origin of man came from the clues offered by the fossil record.

Some fossil specimens seemed to have features that did not reflect as analogous to modern man. For instance, several specimens appeared to have smaller brains. (We compare the characteristic morphological features evidenced in the Fossil craniological record to make predictions about the brains of ancestoral humans.) While not as apparent in intermediate species, characteristics in the latter forms of fossil specimens bore more apparent similarities to those observed in modern man.

It would make sense that the newer forms came after the earlier forms- however -for the fossils that are dated to around similar timeframes, we can also make comparisons between their derived characterisitcs and observe how they link to another. This is how we come to understand which fossils specimens are our human relatives.

The incompleteness of the fossil record had possed challenges wherein intermediaty species are missing, and this is why, with new fossil discoveries, the human phylogeny is sometime redefined. The incompleteness of the fossil record basically means that there are missing and partial specimens. From this, we derive limited information about the progenitor forms. If we find a characteristic part of a fossil specimen such as teeth, we may be able to determine by looking at the characterisitcs of shape, size and thickness, how much the specimen relates to the other forms in the fossil record. Teeth and clues, to spur our scientific inquiry.

What we do see in the human family tree, is that most of the earliest forms appeared on the African continent.
Ardipithecus ramidus, the earliest known member of the human lineage was discovered in 1993 by Tim White, Gen Suwa, and Berhane Asfaw at Aramis, Ethiopia, and dated to 4.4 million years BP. The canine teeth are somewhat reduced from the primitive ape-like condition, but not so much as in Australopithecus (australopithecines); the enamel on the teeth is thin; the deciduous molars are intermediate between those of a human and a chimpanzee. The postcranial skeleton indicates that it was, at least to some degree, bipedal.

Another interesting specimen of the Australopithecine genera, specifically, Australopithecus afarensis, is one of the oldest intermediate specimens in the fossil record, to date-Establishing a fossil timeline of evidence for the age of man and his ancestors.

One primary way in which we can date fossils is by dating the sedimentary layers they are found in, along with the more standard, carbon dating procedure. A. afarenis, also called informally, Lucy, likely originated in East Africa about 3.75 million years ago but it has also been claimed that fragments found in Kenya, of similar bones, appeared as early as 5 million years ago.
Australopithecus africanus was found in South Africa and is said to have lived 2-3 million years ago. Fossil skeletal remains of A. robustus/Paranthropus were also found in Kenya and are said to have lived 2 million years ago. A. robustus/Paranthropus is likely an intermidiate form linking Homo habilis and Homo erectus.
We know that the Australopithecine genera share the common feature of a small brain by studying cranial structures of fossils, as mentioned above. By comparison, we know based on the structure of their hip bones that they were bipedal and had the ability to walk upright similar to modern man.
Bipedal ability became the characteristic that linked certain fossils to a human lineage while the size of the brain was no longer emphasized as a requirement for phylogeny.

In March 2005, a partial skeleton from Ethiopia was claimed to be the world’s oldest bipedal hominid, dating from about 4 million years ago. It has not yet been classified or published in the scientific literature (2010) though it is said to fall between Ardipithecus ramidus and Australopithecus afarensis. It was found about 40 miles from the famous Australopithecus afarensis hominid, Lucy, who lived 3.2 million years ago and is thought to have given rise to the Homo line that ended in modern humans.

Lucy is the matron of our familial heirarchy of close fossil relatives and paradoxically one of the oldest fossils of the homo lineage found to date.
We have the example of a hominid fossil, Homo erectus, initially called Pithecanthropus erecturs and dubbed the nickname, Java man. It is beleived that homo erectus was the first hominid to appear outside of the African continent about 1.8 million years ago.
Notice that the oldest fossils of the homo lineage was discovered in… you guessed it, Africa! This evidence combined with the application of new molecular technologies to the study of archaic and present day genomes, led to the “Out of Africa Hypothesis.” When you consider and think about this hypothesis, think about what the earth may have looked like from a satellite, about 4million years ago. Consider that at one point, all of the continents were grouped into a supercontinent, called Pangaea. How may this have influenced our ancestors? Were they always in Africa? Did they migrate to there? Was it that the conditions in Africa existed in favor of creating fossils? Remember that anywhere fossils are found, there tends to be evidence of catastrophism. It is possible that the geological setting on other  Continents was quieter this part of the world? Think, Gradualism vs. Catastrophism.

Geneticist Luigi Luca Cavalli-Sforza had begun a new area of research by combining concrete findings from demography with a newly available analysis of blood groups in human populations to investigate the origin and diversity of human populations. Building on the work of Cavalli-Sforza, in 1987, Wilson with coworkers Rebecca Cahn and Mark Stoneking announced that they had evidence that the most recent maternal ancestor of all living humans was a woman living in Africa about 200,000 years ago. Based on analysis of mitochondrial DNA (mtDNA) taken from 147 individuals representing different races and geographic origins, this became known as the “Garden of Eden Hypothesis.”
Once again, a new scientific finding caused considerable controversy as well as a lot of misunderstanding of what Mitochondrial Eve represents.

When we study the out of Africa hypothesis, or the Eve hypothesis, named after the biblical Eve- (See, The Adam and Eve Creation Story in the Book of Genesis)-  we learn that mitochondrial DNA is being traced back to a common ancestor. It is important to note that mitochondrial DNA (mDNA)  is only inherited and passed on through the maternal line. (To study patrilineage, we look at haplogroups) Therefore, we must ask ourselves, how did our common female ancestor aquire mitochondrial DNA? It seems that here, the Endosymbiotic hypothesis becomes relevant in ways yet to be explored.  I hypothesize that Lucy is not necessarily our FIRST female common ancestor, insomuch as she is the first ancestor to have acquired mitochondrial DNA through an ancient Eubacterial proliferation leading to genomic integration. This  could have possibly changed the genetic code from that moment on, therefore leading us to believe that the last female ancestor was Lucy.  It seems to me that Lucy is more likely to be the most recent female specimen to have acquired mitochondrial DNA and there may have been progenitors before her.

 

As The fossil record becomes more complete, in-time, with new discoveries, we will continue to learn new things about our ancestors and perhaps more secrets hidden within our genetic code!

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