scigirl
November 3, 2002, 10:46 AM
[quote]Originally posted by Vanderzyden:
I am not asking about replication, or modification, but new gene generation. Please tell me about actual, uncontrovesial evidence which outlines a mechanism for the establishment of completely new genes.<hr></blockquote>
Ok, I want you to realize what you are essentially asking. You are asking for evidence for new genes just spontaneously appearing in our genomes, with no history or explanation as to how they got there, as evidence for evolution?
This makes no sense. It is the creationists who need evidence for genes appearing de novo. Remember that evolution happens in gradual steps – descent with modification. If evolution is true, you should NOT see drastic changes in genomes when you compare related species. If you do see new genes, there should be a reasonable explanation of why that new gene is there (since evolution is limited by what genetic mechanisms can do). And in fact that’s exactly what you do see. Most if not all genes have told us an evolutionary story about themselves. They kept their pedigree papers, if you will. They show us where they came from, and how they got here. And all the genes we study appear to be modifications of older genes. Why is that? If creation is true, and we did not “descend with modification,” than why do all our genes look like they did?
You said it yourself in the Oolon thread – if a programmer wants to subtly modify his program, he rarely has to write code from scratch. He simply modifies the code in the right places. That’s exactly what evolution does (and really, it’s all it can do). Genetic mechanisms ensure variety in the body plans of animals, and selection acts on them in a particular environment. This process, reiterated over millions of years, has given us such marvelous creatures as humans, zebrafish, and yes even the duck-billed platypus. If nature says anything about a theoretical creator, it says that he has a sense of humor (*in other words, he’s not a Baptist!) :D
So I just said that we don’t see genes just appearing out of nowhere. But we DO see new genes duplicating from older genes – through mechanisms such as non-homologous recombination and retrotransposons. Ok here we go – let’s put that Lodish text of yours to work. Since I am a poor student, I did not buy the recommended 4th edition since I already had the 3rd edition. Therefore page numbers will not correlate. But IIRC, the chapter numbers are the same, and your book has about the same stuff as mine.
Turn to Chapter 9, and find the section titled something like Gene Families Are Formed by Gene Duplication and Encode Homologous Proteins
[quote]Frequently, the DNA that lies within 5-10 kb of a particular gene contains sequences that are close but inexact copies of the gene. Such sequences, which are thought to have arisen by duplication of an ancestral gene, are referred to as duplicated protein-coding genes; duplicated genes probably constitute half of the protein-coding DNA in vertebrate genomes. A set of duplicated genes that encode proteins with similar but non-identical amino acid sequences is called a gene family; the encoded closely related, homologous proteins constitute a protein family.<hr></blockquote>
Then Table 9-2 gives some examples of protein families. Now I want to spend some time on one good example of gene duplication which incidentally relates to fetal circulation and the placenta.
[quote]The genes encoding the beta-like globins are a good example of a gene family. Two identical beta-globin polypeptides combine with two identical alpha-globin peptides…to form a hemoglobin molecule…the beta-like globin gene family contains five functional genes designated beta, delta, gammaA, gammaG, and epsilon…All the hemoglobins formed from the different beta-like globins carry oxygen in the blood, but they exhibit somewhat different properties, that are suited to specific roles in human physiology. For example, hemoglobins containing either gammaG or gamma are expressed only during fetal life. Because these fetal hemoglobins have a higher affinity for oxygen than adult hemoglobins, they can effectively extract oxygen from the maternal circulation in the placenta. The lower oxygen affinity of adult hemoglobins, which are expressed after birth, permits better release of oxygen to the tissues, especially muscles, which have a high demand for oxygen during exercise.
The different beta-globin genes probably arose by duplication of an ancestral gene, most likely as the result of an “unequal crossover” during recombination in a germ-cell precursor. Over evolutionary time the two copies of the gene accumulated random mutations; beneficial mutations that conferred some refinement in the basic oxygen-carrying function of hemoglobin were retained by natural selection. Repetitions of this process are thought to have resulted in the evolution of the contemporary globin-like genes observed in humans and other complex species today.<hr></blockquote>
Ok so how does this happen? Lodish doesn’t have a really good figure to point out, so here’s one I made during my debate with Douglas J Bender:
Non-homologous recombination as a mechanism for duplicating genes:
During meiosis, (sperm or egg production), the chromosomes line up along the middle of the cell in a pattern like this:
http://www.cs.montana.edu/~jsaari/chrom4.jpg
See how the arms of the chromosomes are in close proximity. For simplicity I only drew two chromosomes (an ordinary sperm would have 23). Note the pink arms on the blue chromosome. The father and mothers' chromosomes literally became mixed together.
Sometimes this arm swapping does not happen evenly. Here is an unequal crossover:
http://www.cs.montana.edu/~jsaari/chrom5.jpg
http://www.cs.montana.edu/~jsaari/chrom6.jpg
The pink chromosome has no copies of gene D. If this gene is essential, the sperm, or the fetus resulting from that sperm, will probably die. The blue chromosome however has two copies of gene D. This organism will probably survive. Now, one of these genes then is allowed to mutate, as long as the other one stays the same. (Note they could both mutate, but again the progeny will die if an essential gene is lost).
There are other ways to duplicate genes, but non-homologous recombination is the most understood one.
So let’s explain in layman’s terms what gene duplication allows: It gives the cell (or orgainism) more than one copy of the gene, so that one can mutate and play around, as long as the other one stays the same to carry out its current function. However, it would be very surprising to find that every duplicated gene became useful and added a new function. Usually they don’t – and you get what are called “pseudogenes.” These are failed attempts to evolve – the genes became duplicated, but nothing fruitful came of the duplication. There is a section in Lodish titled Pseudogenes are Duplicated Genes that Have Become Nonfunctional
[quote]Two regions in the human beta-like globin gene cluster contain nonfunctional sequences similar to those of the functional beta-like globin genes. Because no known proteins correspond to these regions, they are called pseudogenes. Sequence analysis shows that these copies retain the same apparent exon-intron structure as the functional beta-like genes, suggesting that they also arose by duplication of the same ancestral gene. However, sequence drift during evolution resulted in the accumulation of sequences that either terminate translation or block mRNA processing, rendering such regions non-functional, even if they were transcribed into RNA.
The human delta-globin gene may represent an intermediate in this process of drift. This gene produces very little mRNA, and future sequence drift that completely halts the activity of this infrequently used gene duplicate might well be tolerated by the organism. Such a “silencing” genetic event apparently occurred in the delta gene of gibbons some 5-10 million years ago. The initial mutation was probably in the transcriptional-control region of the delta gene, thus reducing its activity. Enough mutations subsequently accumulated in this gene to render it incapable of directing production of a protein; it thus became a pseudogene. Present-day gibbons survive perfectly well with one adult beta-like globin gene.<hr></blockquote>
Ok that’s a lot of biology to synthesize, but let’s summarize what I have talked about:
1) Descent with modification is made possible only because small genetic changes can create a change in the body plan of the organism. Selection does no good if it has nothing to select on.
2) Gene duplication is an observable, testable event, which can occur during non-homologous recombination.
3) Gene duplication gives the organism a new opportunity – one gene to do the work, and the others to mutate and possibly gain a new function.
4) Sometimes gene duplication works, and you get new functional genes, such as the fetal hemoglobin genes. These additions afford new possibilities for the organism (in this case, the evolution of a placenta).
5) Often though, gene duplication is not fruitful at all (because of the random nature of mutation) and you get pseudogenes. They tried to do something cool, but failed.
Here are some relevant pubmed articles (there are hundreds of articles on this subject by the way):
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11926491&dopt=Abstract" target="_blank">The evolution of the vertebrate beta-globin gene promoter.</a>
[quote] Complexity analysis was therefore used here to identify the modular components (blocks) of the orthologous beta-globin gene promoter sequences of 22 vertebrate species, from zebrafish to humans...It may be inferred that a wide variety of different mutational mechanisms have operated upon the beta-globin gene promoter over evolutionary time...The comparative study of vertebrate beta-globin gene promoter regions described here confirms the generality of the phenomenon of sequence block shuffling and thus supports the view that it could have played an important role in the evolution of differential gene expression.<hr></blockquote>
This paper talks about "promotor shuffling." Promotors are what turn genes on or off (the software analogy you used in the Oolon thread would be analogous to this type of evolutionary mechanism).
Once you have all the different genes, promoter shuffling is the way to turn the right ones on and off at the right times. This is evidence that promoter shuffling has occurred during evolution.
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11919282&dopt=Abstract" target="_blank">Cytoglobin: a novel globin type ubiquitously expressed in vertebrate tissues.</a>
[quote] Here we report the identification of a fourth and novel type of globin in mouse, man, and zebrafish. It is expressed in apparently all types of human tissue and therefore has been called cytoglobin (CYGB)...Mouse and human CYGBs comprise 190 amino acids; the zebrafish CYGB, 174 amino acids. The human CYGB gene is located on chromosome 17q25. The mammalian genes display a unique exon-intron pattern with an additional exon resulting in a C-terminal extension of the protein, which is absent in the fish CYGB. Phylogenetic analyses suggest that the CYGBs had a common ancestor with vertebrate myoglobins. This indicates that the vertebrate myoglobins are in fact a specialized intracellular globin that evolved in adaptation to the special needs of muscle cells.<hr></blockquote>
Another member of this globin family, which, once it evolved, allowed vertebrates have more specialized muscle cells.
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11158601&dopt=Abstract" target="_blank">An orphaned mammalian beta-globin gene of ancient evolutionary origin.</a>
[quote]Mammals possess multiple, closely linked beta-globin genes that differ in the timing of their expression during development. These genes have been thought to be derived from a single ancestral gene, by duplication events that occurred after the separation of the mammals and birds. We report the isolation and characterization of an atypical beta-like globin gene (omega-globin) in marsupials that appears to be more closely related to avian beta-globin genes than to other mammalian beta-globin genes, including those previously identified in marsupials. Phylogenetic analyses indicate that omega-globin evolved from an ancient gene duplication event that occurred before the divergence of mammals and birds. Furthermore, we show that omega-globin is unlinked to the previously characterized beta-globin gene cluster of marsupials, making this the first report of an orphaned beta-like globin gene expressed in a vertebrate.<hr></blockquote>
Yet another duplicated globin gene that correlates with our current evolutionary trees.
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11093835&dopt=Abstract" target="_blank">Gene conversion may aid adaptive peak shifts.</a>
[quote]Gene conversion is often viewed as a homogenizing force that opposes adaptive evolution. The objective of this study is to suggest a potential role for gene conversion in adaptive evolution of proteins through aiding the transfer of a population from one adaptive peak to another. Our hypothesis starts with the observation that a tandem gene duplication may result in an extra gene copy that is released from selective constraints. In such cases, individually deleterious mutations may accumulate on the extra copy of the gene, and through gene conversion these mutations may subsequently be presented to the functioning gene for selection en masse. Thus, groups of mutations that jointly confer a selective advantage may regularly be made available for selection. We present a mathematical model of this process and identify the range of rates of gene conversion, gene duplication and mutation under which it may operate. The results indicate that the process may be biologically feasible if the rate of appearance of the potentially beneficial mutations is not too small in relation to the rates of null mutation and of gene conversion. This process appears to be a possible mechanism for effecting adaptive peak shifts in large populations. We show that all the evolutionary steps in the proposed model may have occurred in the evolution of primate gamma -globin genes. We suggest that hide-and-release mechanisms for genetic variation may constitute a more general principal of evolvability. <hr></blockquote>
A mathematical model that shows gene duplication is a viable mechanism for evolution.
I think that’s enough for now. Any questions?
scigirl
* I have no idea what religion Vanderzyden is, this was more a poke at the Baptist Board, whom I found to be way too serious!
I am not asking about replication, or modification, but new gene generation. Please tell me about actual, uncontrovesial evidence which outlines a mechanism for the establishment of completely new genes.<hr></blockquote>
Ok, I want you to realize what you are essentially asking. You are asking for evidence for new genes just spontaneously appearing in our genomes, with no history or explanation as to how they got there, as evidence for evolution?
This makes no sense. It is the creationists who need evidence for genes appearing de novo. Remember that evolution happens in gradual steps – descent with modification. If evolution is true, you should NOT see drastic changes in genomes when you compare related species. If you do see new genes, there should be a reasonable explanation of why that new gene is there (since evolution is limited by what genetic mechanisms can do). And in fact that’s exactly what you do see. Most if not all genes have told us an evolutionary story about themselves. They kept their pedigree papers, if you will. They show us where they came from, and how they got here. And all the genes we study appear to be modifications of older genes. Why is that? If creation is true, and we did not “descend with modification,” than why do all our genes look like they did?
You said it yourself in the Oolon thread – if a programmer wants to subtly modify his program, he rarely has to write code from scratch. He simply modifies the code in the right places. That’s exactly what evolution does (and really, it’s all it can do). Genetic mechanisms ensure variety in the body plans of animals, and selection acts on them in a particular environment. This process, reiterated over millions of years, has given us such marvelous creatures as humans, zebrafish, and yes even the duck-billed platypus. If nature says anything about a theoretical creator, it says that he has a sense of humor (*in other words, he’s not a Baptist!) :D
So I just said that we don’t see genes just appearing out of nowhere. But we DO see new genes duplicating from older genes – through mechanisms such as non-homologous recombination and retrotransposons. Ok here we go – let’s put that Lodish text of yours to work. Since I am a poor student, I did not buy the recommended 4th edition since I already had the 3rd edition. Therefore page numbers will not correlate. But IIRC, the chapter numbers are the same, and your book has about the same stuff as mine.
Turn to Chapter 9, and find the section titled something like Gene Families Are Formed by Gene Duplication and Encode Homologous Proteins
[quote]Frequently, the DNA that lies within 5-10 kb of a particular gene contains sequences that are close but inexact copies of the gene. Such sequences, which are thought to have arisen by duplication of an ancestral gene, are referred to as duplicated protein-coding genes; duplicated genes probably constitute half of the protein-coding DNA in vertebrate genomes. A set of duplicated genes that encode proteins with similar but non-identical amino acid sequences is called a gene family; the encoded closely related, homologous proteins constitute a protein family.<hr></blockquote>
Then Table 9-2 gives some examples of protein families. Now I want to spend some time on one good example of gene duplication which incidentally relates to fetal circulation and the placenta.
[quote]The genes encoding the beta-like globins are a good example of a gene family. Two identical beta-globin polypeptides combine with two identical alpha-globin peptides…to form a hemoglobin molecule…the beta-like globin gene family contains five functional genes designated beta, delta, gammaA, gammaG, and epsilon…All the hemoglobins formed from the different beta-like globins carry oxygen in the blood, but they exhibit somewhat different properties, that are suited to specific roles in human physiology. For example, hemoglobins containing either gammaG or gamma are expressed only during fetal life. Because these fetal hemoglobins have a higher affinity for oxygen than adult hemoglobins, they can effectively extract oxygen from the maternal circulation in the placenta. The lower oxygen affinity of adult hemoglobins, which are expressed after birth, permits better release of oxygen to the tissues, especially muscles, which have a high demand for oxygen during exercise.
The different beta-globin genes probably arose by duplication of an ancestral gene, most likely as the result of an “unequal crossover” during recombination in a germ-cell precursor. Over evolutionary time the two copies of the gene accumulated random mutations; beneficial mutations that conferred some refinement in the basic oxygen-carrying function of hemoglobin were retained by natural selection. Repetitions of this process are thought to have resulted in the evolution of the contemporary globin-like genes observed in humans and other complex species today.<hr></blockquote>
Ok so how does this happen? Lodish doesn’t have a really good figure to point out, so here’s one I made during my debate with Douglas J Bender:
Non-homologous recombination as a mechanism for duplicating genes:
During meiosis, (sperm or egg production), the chromosomes line up along the middle of the cell in a pattern like this:
http://www.cs.montana.edu/~jsaari/chrom4.jpg
See how the arms of the chromosomes are in close proximity. For simplicity I only drew two chromosomes (an ordinary sperm would have 23). Note the pink arms on the blue chromosome. The father and mothers' chromosomes literally became mixed together.
Sometimes this arm swapping does not happen evenly. Here is an unequal crossover:
http://www.cs.montana.edu/~jsaari/chrom5.jpg
http://www.cs.montana.edu/~jsaari/chrom6.jpg
The pink chromosome has no copies of gene D. If this gene is essential, the sperm, or the fetus resulting from that sperm, will probably die. The blue chromosome however has two copies of gene D. This organism will probably survive. Now, one of these genes then is allowed to mutate, as long as the other one stays the same. (Note they could both mutate, but again the progeny will die if an essential gene is lost).
There are other ways to duplicate genes, but non-homologous recombination is the most understood one.
So let’s explain in layman’s terms what gene duplication allows: It gives the cell (or orgainism) more than one copy of the gene, so that one can mutate and play around, as long as the other one stays the same to carry out its current function. However, it would be very surprising to find that every duplicated gene became useful and added a new function. Usually they don’t – and you get what are called “pseudogenes.” These are failed attempts to evolve – the genes became duplicated, but nothing fruitful came of the duplication. There is a section in Lodish titled Pseudogenes are Duplicated Genes that Have Become Nonfunctional
[quote]Two regions in the human beta-like globin gene cluster contain nonfunctional sequences similar to those of the functional beta-like globin genes. Because no known proteins correspond to these regions, they are called pseudogenes. Sequence analysis shows that these copies retain the same apparent exon-intron structure as the functional beta-like genes, suggesting that they also arose by duplication of the same ancestral gene. However, sequence drift during evolution resulted in the accumulation of sequences that either terminate translation or block mRNA processing, rendering such regions non-functional, even if they were transcribed into RNA.
The human delta-globin gene may represent an intermediate in this process of drift. This gene produces very little mRNA, and future sequence drift that completely halts the activity of this infrequently used gene duplicate might well be tolerated by the organism. Such a “silencing” genetic event apparently occurred in the delta gene of gibbons some 5-10 million years ago. The initial mutation was probably in the transcriptional-control region of the delta gene, thus reducing its activity. Enough mutations subsequently accumulated in this gene to render it incapable of directing production of a protein; it thus became a pseudogene. Present-day gibbons survive perfectly well with one adult beta-like globin gene.<hr></blockquote>
Ok that’s a lot of biology to synthesize, but let’s summarize what I have talked about:
1) Descent with modification is made possible only because small genetic changes can create a change in the body plan of the organism. Selection does no good if it has nothing to select on.
2) Gene duplication is an observable, testable event, which can occur during non-homologous recombination.
3) Gene duplication gives the organism a new opportunity – one gene to do the work, and the others to mutate and possibly gain a new function.
4) Sometimes gene duplication works, and you get new functional genes, such as the fetal hemoglobin genes. These additions afford new possibilities for the organism (in this case, the evolution of a placenta).
5) Often though, gene duplication is not fruitful at all (because of the random nature of mutation) and you get pseudogenes. They tried to do something cool, but failed.
Here are some relevant pubmed articles (there are hundreds of articles on this subject by the way):
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11926491&dopt=Abstract" target="_blank">The evolution of the vertebrate beta-globin gene promoter.</a>
[quote] Complexity analysis was therefore used here to identify the modular components (blocks) of the orthologous beta-globin gene promoter sequences of 22 vertebrate species, from zebrafish to humans...It may be inferred that a wide variety of different mutational mechanisms have operated upon the beta-globin gene promoter over evolutionary time...The comparative study of vertebrate beta-globin gene promoter regions described here confirms the generality of the phenomenon of sequence block shuffling and thus supports the view that it could have played an important role in the evolution of differential gene expression.<hr></blockquote>
This paper talks about "promotor shuffling." Promotors are what turn genes on or off (the software analogy you used in the Oolon thread would be analogous to this type of evolutionary mechanism).
Once you have all the different genes, promoter shuffling is the way to turn the right ones on and off at the right times. This is evidence that promoter shuffling has occurred during evolution.
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11919282&dopt=Abstract" target="_blank">Cytoglobin: a novel globin type ubiquitously expressed in vertebrate tissues.</a>
[quote] Here we report the identification of a fourth and novel type of globin in mouse, man, and zebrafish. It is expressed in apparently all types of human tissue and therefore has been called cytoglobin (CYGB)...Mouse and human CYGBs comprise 190 amino acids; the zebrafish CYGB, 174 amino acids. The human CYGB gene is located on chromosome 17q25. The mammalian genes display a unique exon-intron pattern with an additional exon resulting in a C-terminal extension of the protein, which is absent in the fish CYGB. Phylogenetic analyses suggest that the CYGBs had a common ancestor with vertebrate myoglobins. This indicates that the vertebrate myoglobins are in fact a specialized intracellular globin that evolved in adaptation to the special needs of muscle cells.<hr></blockquote>
Another member of this globin family, which, once it evolved, allowed vertebrates have more specialized muscle cells.
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11158601&dopt=Abstract" target="_blank">An orphaned mammalian beta-globin gene of ancient evolutionary origin.</a>
[quote]Mammals possess multiple, closely linked beta-globin genes that differ in the timing of their expression during development. These genes have been thought to be derived from a single ancestral gene, by duplication events that occurred after the separation of the mammals and birds. We report the isolation and characterization of an atypical beta-like globin gene (omega-globin) in marsupials that appears to be more closely related to avian beta-globin genes than to other mammalian beta-globin genes, including those previously identified in marsupials. Phylogenetic analyses indicate that omega-globin evolved from an ancient gene duplication event that occurred before the divergence of mammals and birds. Furthermore, we show that omega-globin is unlinked to the previously characterized beta-globin gene cluster of marsupials, making this the first report of an orphaned beta-like globin gene expressed in a vertebrate.<hr></blockquote>
Yet another duplicated globin gene that correlates with our current evolutionary trees.
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11093835&dopt=Abstract" target="_blank">Gene conversion may aid adaptive peak shifts.</a>
[quote]Gene conversion is often viewed as a homogenizing force that opposes adaptive evolution. The objective of this study is to suggest a potential role for gene conversion in adaptive evolution of proteins through aiding the transfer of a population from one adaptive peak to another. Our hypothesis starts with the observation that a tandem gene duplication may result in an extra gene copy that is released from selective constraints. In such cases, individually deleterious mutations may accumulate on the extra copy of the gene, and through gene conversion these mutations may subsequently be presented to the functioning gene for selection en masse. Thus, groups of mutations that jointly confer a selective advantage may regularly be made available for selection. We present a mathematical model of this process and identify the range of rates of gene conversion, gene duplication and mutation under which it may operate. The results indicate that the process may be biologically feasible if the rate of appearance of the potentially beneficial mutations is not too small in relation to the rates of null mutation and of gene conversion. This process appears to be a possible mechanism for effecting adaptive peak shifts in large populations. We show that all the evolutionary steps in the proposed model may have occurred in the evolution of primate gamma -globin genes. We suggest that hide-and-release mechanisms for genetic variation may constitute a more general principal of evolvability. <hr></blockquote>
A mathematical model that shows gene duplication is a viable mechanism for evolution.
I think that’s enough for now. Any questions?
scigirl
* I have no idea what religion Vanderzyden is, this was more a poke at the Baptist Board, whom I found to be way too serious!