What Separates Humans from Prosimians?

[This post is part of a series, What Separates Humans from the Animals?]


Before we look at a difference between us and prosimians (lemurs, bushbabies, etc), we need to briefly touch on three genetic concepts. I've tried to make them as painless as possible.

Concept #1: Stop Codons. DNA is made of 4 basic molecules (nucleotides) that are represented by the letters A, T, G, and C. In a gene, every 3 nucleotides codes for an amino acid (the building blocks of proteins). However, there are several combinations that mean, 'Stop. This is the end of the gene.' These are called 'stop codons' and mutations can do two things with respect to them: (i) a mutation in a gene can create a premature stop codon, thus truncating the protein product, or (ii) a mutation can erase a stop codon, thus extending the coding of the gene until a random stop codon in the downstream sequence is reached.

Concept #2: Introns and Exons. Most of your genes are actually fragmented into pieces called exons. After the DNA is transcribed into RNA--but before the RNA is translated into protein--the extra parts (introns) are cut out and the exons are spliced together. The following image from Wikipedia conveys the idea:




The take-home message here is that the introns (the blue lines) were cut out before the RNA was used to make a protein. Simply put, there are signals in the sequence that tell enzymes where the introns are and where the ends of the exons are that should be joined together.

Concept #3: Transposons. Take a course on bacterial genetics and you will be introduced to transposons. Transposons are selfish-DNA elements that are kind of like viruses, except the don't jump from cell to cell. Rather, they spread copies within the genome. They come in various types and have different mechanisms of replication. Your basic cut-and-paste transposon has a simple structure. It consists of a transposase gene, which does the cutting and pasting of DNA, and flanking inverted repeats, which the transposase recognizes. I've made a diagram illustrating the structure and movement of a simple transposon.



Many organisms other than bacteria have transposons in their genome, including us. However, in our case they seem to be remnants of the past because they have sustained mutations that have rendered them inactive. There are other mobile genetic elements in our genome that are different from transposons, but similar in general concept.

Alright, let's proceed.

The basic background to this story is that a gene was discovered in the human genome that is a chimera of a known gene (SET), and a transposase gene from a transposon called Hsmar1. Humans, other apes, and monkeys all have this chimeric gene, which is called SETMAR. Prosimians and other placental mammals only have the SET part, without the addition of the transposase. So the presence of SETMAR sets us apart from prosimians and all other distantly related mammals. So how did SETMAR come to be?

Cordaux et al looked at it and figured out how to get from SET to SETMAR in a few simple steps. I will be referring to their Figure 1. (Click to enlarge.)

Fig. 1. Milestones leading to the birth of SETMAR. The structure of the SETMAR locus (Right) and a simplified chronology of the divergence time of the species examined relative to hominoid primates (Left) are shown. Pink boxes represent the two SET exons, which are separated by a single intron (interrupted black line) and form a “SET-only” gene whose structure is conserved in all nonanthropoid species examined and terminated with a stop codon (∗) located at a homologous position (except in cow; see Fig. 2 a). The Hsmar1 transposon (event 1) was inserted in the primate lineage, after the split between tarsier and anthropoids, but before the divergence of extant anthropoid lineages. The transposon is shown here with its TIRs (black triangles) and transposase coding sequence (red box). The secondary AluSx insertion within the TIR of Hsmar1 (event 2) is represented as a blue diamond. The position of the deletion removing the stop codon of the “SET-only” gene (event 3) is indicated as a lightning bolt. The de novo conversion from noncoding to exonic sequence is shown in green, the creation of the second intron is represented as a dashed blue line (event 4), and the splice sites are shown as thick blue lines.

We'll start at the bottom and work our way up.

Starting point: Other mammals--up to prosimians, have a SET gene that has two exons. The dashed lines indicate sequence that is spliced out of RNA before a protein is made (see Concept #2 above).

Step 1: An Hsmar1 transposon inserted just downstream of the SET gene.

Step 2: An Alu element inserted into one of the Hsmar1 inverted repeats. (I've written about Alu elements before--see here. Briefly, they are like transposons but do not contain any genes, themselves.) The Hsmar1 transposon is now stuck in place; it cannot cut itself out because one of its inverted repeats has been partially deleted.

Step 3: A small deletion occurred, which removed the stop codon at the end of the SET second exon, thus extending the exon (see concept #1 above).

Step 4: The extended SET exon included sequence that could then act as a signal for RNA splicing following transcription. The Hsmar1 transposon also contained a splice signal, so the end of SET could be spliced to Hsmar1.

Finish: The final protein product consists of the original SET, plus a few amino acids gained from the extension of the second exon, plus the transposase gene from the Hsmar1 transposon. Thus a new chimeric gene, SETMAR is born.

The creation of the new gene occurred after the group of primates that gave rise to monkeys and apes diverged from prosimians. Of course, these steps did not all occur in an individual animal!

What does SETMAR do? The answer to that is not yet clear. The SET portion is known to modify histones, which are proteins that provide structural support to DNA and can help determine whether a gene is expressed or not. Interestingly, although the transposase has two functions, natural selection seems to be selecting only one of them: the ability to bind DNA, especially the inverted repeats. Putting the two together suggests that the protein helps to regulate gene expression at specific places in the genome. However, for our purposes here, the function of SETMAR does not matter.

The the main point is that we, other apes, and monkeys have a novel gene that prosimians and other mammals do not, and that the genetic structure of the gene gives us clues as to how it was created: co-option of naturally occurring genetic processes.


Reference:

Cordaux R, Udit S, Batzer MA, Feschotte C. Birth of a chimeric primate gene by capture of the transposase gene from a mobile element. Proc Natl Acad Sci U S A. 2006 May 23;103(21):8101-6.

---

Continue reading...

Henry Eyring, Galileo, and Adam

As I was reading Galileo's Daughter I was struck by an interesting choice of words. An anonymous snitch reported on an Archbishop's praise for Galileo:

The Archbishop has told many that Galileo was unjustly sentenced by this Holy Congregation, that he is the first man in the world, that he will live forever in his writings...

What did he mean that Galileo was the "first man in the world?" Of course Moses 3:7 came to mind, "And man became a living soul, the first flesh upon the earth, the first man also."

'First' often means to precede others in time or order. But it can also mean to precede others in importance, or to be the most prominent member of a group.

With that in mind, consider a statement from the correspondence of Henry Eyring that is quoted in the recent biography, Mormon Scientist: The Life and Faith of Henry Eyring (pg. 269). A portion of the excerpted letter is quoted below.

We are not told who Adam's father was. To me the important thing is that Adam is the spirit child of God. He came into this world when he received a mortal body. The Fall consisted of becoming subject to death, and everyone born into the world is subject to death and so partakes of this fallen state with Adam. Finally, through the atonement we will all receive a resurrected body.

Whether Adam's father lived on this earth or somewhere else would seem of secondary importance to me. Adam was the one whom God recognized as presiding over the first dispensation and as such, with Eve his wife, became our first parents.

When it came to Adam and Eve, apparently Henry Eyring was open to alternate definitions of 'first.'

---

Continue reading...

Temple Astronomical Impossibilities

This has been a good year of backyard astronomy for me. Not only do I live somewhere with relatively little light pollution, but my bedroom window faces south-southeast which allows me an easy view of the ecliptic and the southern constellations. This also means that the moon shines right into my bedroom.

It's funny how you can know and understand a concept, but then come to an unexpected fuller understanding by coming it at it from a different angle. This has been my recent experience with the phases of the moon. I already knew that the phases are a result of the moon revolving around the earth--and that our view of reflected sunlight differs accordingly. But it wasn't until I consistently observed the moon that I realized that different phases of the moon correlated with particular times of day. This also means that the rising and setting of the moon changes relative to the sun in a consistent way (see example below).

Apparently the makers of one of the films shown in the temple didn't realize this either as it depicts a full moon hanging above a horizon where the sun has set (presumably--it also could be about to rise). That simply cannot happen; if the moon were that close to the sun in the sky, it would be a crescent (waxing if it followed the sun down; waning if it preceded the sun rising). The moon is full when it is on the opposite side of the earth relative to the sun.

I'm sorry to say that I did not catch the problem. I only recently made the new connection, and in one of life's funny coincidences, a member of my ward noticed the incongruity and brought it to my attention last week. I have noticed a rumbling sound as a planet passes by. Rumbling in the vacuum of space? I don't think so.

So now you have something new to look for the next time you go to the temple.

---

Sunrise/Moonrise Example:

Consider the lunar cycle beginning Oct 28 (all times as Eastern Standard Time). Notice that at New Moon the sun and moon essentially rise together, whereas by Full Moon the moon has fallen behind the sun by ~10 hours (times obtained here):

Oct 28: New Moon
Sunrise: 6:31 a.m
Moonrise: 6:17 a.m.

Nov 6: First Quarter
Sunrise: 6:41 a.m.
Moonrise: 1:23 p.m.

Nov 13: Full Moon
Sunrise: 6:49 a.m.
Moonrise: 4:59 p.m.

Nov 19: Last Quarter
Sunrise: 6:56 a.m.
Moonrise: 11:54 p.m.

---

Continue reading...

National Myth-Making

Discover Magazine has an article online, "The Man Who Went Up a Hill and Came Down a Pyramid," that reports on some hills in Bosnia that are becoming a national myth (in all the meanings of the word). The short version is that a guy with no relevant credentials thinks that some hills in Bosnia are actually ancient pyramids built before the ice age, that the purported ancient civilization that built them was more advanced (whatever that means) than we are...and the pseudoscience continues from there. It may even launch a New Age religion.

Of course this is driving actual geologists and archaeologists nuts. The story has been unfolding since 2005, and if this article is a reliable guide, Bosnia is really going in for it.

If so many prominent scientists hold that there are no Bosnian pyramids, why is Osmanagich’s project so successful? One reason is that at the time of his return to Bosnia in 2005, there was a knowledge vacuum unlike any the country had ever experienced before. The legions of archaeologists who would have challenged his theory before the 1992–1995 war, says Cambridge archaeologist Preston Miracle, were not around. In the prewar years, “archaeology in Bosnia was truly world-class,” he says. But by the time of the war, many of these leading scholars had died, and during the war many promising Bosnian archaeology students fled, settling into permanent positions at universities abroad. Today, many experts say, Bosnia’s real archaeological record is, at best, neglected—and at worst, endangered.

The pyramids are becoming a symbol of national pride as well as a source of tourism income. We may be watching the seeds of a future historical (heh, oxymoron) controversy taking root before our eyes.

---

Continue reading...

McCain-Palin's Unique Consultant

John McCain's favorite examples of frivolous government spending have included a genetic study of grizzly bears, and replacing the 40-year-old projector at the Adler Planetarium in Chicago. (Actually, the projector money never materialized.)

Now Sarah Palin has taken aim at fruit flies.




Of course, the field of genetics was pretty much founded with fruit flies, and they are still a favorite model organism for genetics, development, etc. From what I can find online, the fruit fly research Palin objects to appears to be agricultural in nature. But I think I know why science is taking the brunt of pork-barrel spending ridicule: Unfrozen Caveman Lawyer is on the McCain-Palin consulting team.

"Ladies and gentlemen of the jury, I'm just a caveman. I fell on some ice and was later thawed by some of your scientists. Your world frightens and confuses me! Sometimes when I fly to Europe on the Concorde, I wonder, am I inside some sort of giant bird? Am I gonna be digested? I don't know, because I'm a caveman, and that's the way I think! When I'm courtside at a Knicks game, I wonder if the ball is some sort of food they're fighting over. When I see my image on the security camera at the country club, I wonder, are they stealing my soul? I get so upset, I hop out of my Range Rover, and run across the fairway to to the clubhouse, where I get Carlos to make me one of those martinis he's so famous for, to soothe my primitive caveman brain. But whatever world you're from, I do know one thing..."

..that if fruit flies threaten the olive industry in California, they should not be studied in France?

Seriously, these project examples may or may not have merit. But why can't they frame the issue in terms of projects competing for grant money from appropriate agencies--where they are evaluated for merit against other proposals--instead being funded directly from earmarks (assuming that is what they would prefer)? Why must they directly ridicule these projects--as though even a caveman knows that they are a waste of money--and what kind of message does that send about science?

---

Continue reading...

What Separates Humans from Egg-layers?

Part of what makes the platypus seem strange is that it lays eggs--like amphibians, reptiles, and birds--and yet it is a mammal. In contrast, like many other mammals we give birth to live young which receive nourishment during development by means of a placenta instead of from egg yolk. We have no need for the yolk protein vitellogenin; we don't make it, nor do we have the gene (or genes--there can be multiple copies) for it. The presence of vitellogenin sets egg-laying animals apart from us placentals. Or if you want to put it the other way, the absence of vitellogenin separates us from egg-layers. But there is more to the story, of course.

A quick digression: Did you know that when you 'delete' a file on a computer disk, what you have really done is tell the operating system not to recognize the file anymore? The data in the file remains on the disk until the space is overwritten by a different file. In fact there are programs that can find and resurrect deleted files.

Genomes can be like that and, wouldn't you know it, the remains of vitellogenin are in our genome, as well as the genomes of other placental animals. Genes that have become broken and degraded by mutation are called pseudogenes, and there are bits and pieces of between one and three vitellogenin pseudogenes in the human genome. (The number is debatable because two of the copies are degraded to the point of being difficult to statistically distinguish from background sequence.) Perhaps the clearest illustration of this is Figure S2 from Brawand et al, which shows an alignment of a portion of one of the vitellogenin genes (VIT1) from four species. (Click for larger view.)

Figure S2. Sequence Alignment of the VIT1 Exon 3 from Human (Homo sapiens), Dog (Canis familiaris), Armadillo (Dasypus novemcinctus), and Chicken (Gallus gallus). The alignment shows two indels that are shared between human, dog, and armadillo, indicating inactivation of these genes in the common ancestor of these species (see main text for discussion).

The figure shows an alignment of sequences from the genome of chicken, human, dog, and armadillo, with chicken as the standard of comparison (since it's VIT1 gene is in tact.) I added the green arrows to draw attention to the deletions shared by human, dog, and armadillo. That the deletions are shared by all three suggests that they occurred in common ancestors, and that this was a pseudogene before the lineages that gave rise to the three species diverged. The asterisks indicate positions where all four sequences are identical.

Now the genome is a big place, and you could argue that if you search hard enough you will find a spurious sequence that yields some alignment to the chicken vitellogenin genes. However, the authors also found alignment in the sequences flanking the VIT genes, which provides added support to the authenticity of the alignment. This is represented in Figure 2 as a dot plot comparing human and chicken sequence. (Click for larger view.)

Figure 2. Genome Alignment (Dot Plot Representing SIM Alignments) of Human/Chicken Syntenic Regions VIT 1-VIT3 Regions. The chain with the best cumulative score is shown. Alignment of flanking genes confirms the synteny of the aligned regions. The combined alignments of VIT1 coding sequences showed significantly higher alignment scores than the genomic background (introns and intergenic regions) in the chain, as assessed by a Mann-Whitney U test (p < 0.05). Thus, we can statistically exclude that detected VIT1 remnants from humans represent spurious sequence matches. The coding sequence matches for VIT2/3 may be too short to provide statistical significance or partially spurious.

Black dots represent identical sequence, and you can see--especially in the top panel--that there is some significant alignment with not only VIT1, but with ELTD1 as well. So not only do portions of the VIT genes align, but they are found in the same context relative to other genes. Again, this gives added support to their authenticity.

So the presence/absence of vitellogenin indeed sets us apart from egg-laying animals. But at the same time it paradoxically ties us together.


Reference:

Brawand D, Wahli W, Kaessmann H (2008) Loss of Egg Yolk Genes in Mammals and the Origin of Lactation and Placentation. PLoS Biol 6(3): e63

---

Continue reading...

What Separates Humans from the Animals?

In 1857 the famous anatomist and opponent of Darwin, Richard Owen, claimed to have found a brain structure in humans that was missing in other apes. In his view this set humans apart and justified their classification in a separate genus. T.H. Huxley thought that Owen's claim was based on an artifact of poorly preserved specimens, and in a scientific meeting in 1860, Huxley humiliated Owen by presenting evidence that contradicted him. It turned out that Huxley was right; there was no such distinction in gross brain anatomy.

But humans are different in various ways from other animals, and in a coming series of posts I will highlight some distinguishing genetic features. However, whereas Richard Owen labored to discredit Darwin's hypothesis of common descent, the examples I have chosen support it, as I hope will be clear. These examples are drawn from the scientific literature and I hope that you will find them interesting. Enjoy!

Posts in Series:

1. What Separates Humans from Egg-layers?
2. What Separates Humans from Prosimians?
3. What Separates Humans from New World Monkeys?
4. What Separates Humans from Monkeys? (Resurrection Edition)
5. What Separates Humans from Orangutans?
6. What Separates Humans from Chimpanzees? (Part 1)

---

Continue reading...

The Time My Mother Made Duane Jeffery Nervous

Life has been busy lately, so it has been a little slow here. I have some good stuff in the works, but in the meantime here is a fun anecdote:

My parents met and married at BYU. Dad was on a sports scholarship and was sometimes on the road competing, so Mom would go to his classes and take notes for him. One semester Dad had a class from Duane Jeffery, and Mom dutifully attended as needed. When she showed up with a tape recorder, Dr. Jeffery was apparently concerned--enough to ask her what she was up to. Her explanation evidently satisfied him, because he said O.K. and that was that.

I don't know whether he was really concerned or not, but I wouldn't blame him if he was. Not many years previous Ernest Wilkinson had used students to spy on troublesome professors, and later on at least one occasion, comments allegedly critical of the Church that Dr. Jeffery made at an informal gathering were brought to the attention of "church officials," after which he was asked write "a letter reaffirming his commitment to the church."

For what it's worth, Dad has positive memories of Duane Jeffery, and he thinks he still has some of those recordings. (Sadly, I never had a class from Dr. Jeffery. In fact I don't think I even really knew who he was until after I graduated.)

---

Continue reading...