Anthropology 105

The bone of the upper arm is called the humerus. It articulates with the scapula at the shoulder joint, and the radius and ulna at the elbow.

The proximal end of the humerus is dominated by a half-spherical articular surface, called the head, that forms the ball of the ball-and-socket joint of the shoulder. The head points medially into the shoulder joint. On the lateral side, a bump called the greater tubercle projects proximally.

The distal end of the humerus has two articular surfaces. The first of these, called the trochlea, is a pulley-shaped surface that accommodates the ulna. The other, called the capitulum, is a small spherical structure lateral to the trochlea that articulates with the head of the radius. The capitulum is on the lateral side, the trochlea is medial.

On the posterior surface, above the trochlea is a large dent, called the olecranon fossa. The proximal end of the ulna fits into this fossa when the elbow is extended.

What to do: At this station are many right and left humeri, including some fragmentary bones. Work on telling right and left humeri from each other. You will find the distal end of the bone very helpful, with the trochlea medial and capitulum lateral, and the olecranon fossa on the posterior aspect.

Each vertebra has several parts. The most important are:

Body

The largest part of the vertebra, this is a cylindrical column of spongy bone, padded by cartilaginous discs above and below.

Vertebral foramen

The hole in the center of the vertebra, through which passes the spinal cord.

Spinous process

A projection on the posterior aspect of the bone, together these form the ``spine'' that can be felt from outside the skin.

Transverse processes

Left and right, these project from the vertebra allowing muscular and ligamentous attachments.

Additionally, the first two vertebrae below the head are special in their anatomy. The first, called the atlas, holds up the head and lacks any vertebral body. Its anatomy is like a simple ring of bone. The second, the axis has a large projection from its superior surface, called the dens, or odontoid process, which stabilizes rotation of the neck.

The rest of the vertebrae are slightly different from each other, depending on the part of the spine. The transverse processes of the cervical vertebrae tend to be split, or bifid, as are the spinous processes of C3-C6. The thoracic vertebrae have articular surfaces for the ribs, called rib facets, and their spinous processes are long and directed downward (caudally). The lumbar vertebrae have very large and thick vertebral bodies and stout spinous processes.

A genetic map shows the location of genes and other DNA elements on a chromosome. The Human Genome Project created a genetic map that lists more than 3 billion nucleotides of DNA in an order that represents a partial consensus of many human DNA sequences. This map continues to be refined as we develop more understanding of human DNA structure and variation. The results are openly available to the public for download or analysis.

We can examine this human genetic map by using a tool called a genome browser. One of the best-known genome browsers was constructed and is maintained by the Genome Bioinformatics Group of the University of California-Santa Cruz, called the UCSC Genome Browser. The tool can be found on the web at http://genome.ucsc.edu/cgi-bin/hgGateway, and a broader set of genome tools can be found at the home page, http://genome.ucsc.edu/

One of the most widely known molecular structures is hemoglobin. Normal hemoglobin in human red blood cells is labeled HbA. Hemoglobin is not a protein, but a structure of four proteins bound with a smaller molecule called heme. An iron atom in the heme can bind oxygen, so that hemoglobin can transport oxygen throughout the body. The heme is strongly associated with one each of α and β protein subunits. Because HbA includes four subunits, two α and two β, it can be denoted α₂β₂.

The protein subunits of hemoglobin are each encoded by a separate gene. We are going to explore the regions around these two genes, HBA1 (α-globin) and HBB (β-globin).

Some representative screenshots from the UCSC Genome Browser. The middle picture shows the whole length of the database entry for HBB, while the bottom shows the view zoomed in to the base level. Both screenshots were taken with all genome browser tracks turned off except for the UCSC Genes track.

1. Open a browser window with the UCSC Genome Browser search page.
2. Enter "beta globin" as the search term.
3. The results page will give a list of several genes as possible matches. The first on the list is HBB, which is the β-globin gene. Choose it.
4. The browser will now show you a graphic representing the region of the HBB gene. At any time, you can enter HBB into the "gene" query box to return to this location.
5. The result will look something like this:


Genome browser result for HBB, showing the length of the whole gene. The only database track in this result is "UCSC Genes", all others are turned off.

6. The "position" box and the chromosome ideogram both show which chromosome we are looking at: Chromosome 11. The scale at the top of the genetic map will tell you the range of positions that is covered by the coding sequence of HBB. At the top of the figure, you can see the positions, here running from 5,203,500 past 5,204,500 — more than a thousand bases across, in other words.
7. HBB has three exons, or coding intervals, and these are indicated in the figure by the darker bars. The three dark bars are connected by thin lines that represent the two non-coding intervals, or introns. The HBB gene runs from right to left in the figure, as indicated by the small "arrow feathers" coming off the line running through the exons. In addition, the database has a second entry for HBB, which comes from an alternative transcript found in some tissue samples.
8. Click the button that says "base", or zoom in by dragging the mouse across a small part of the gene display. You should be able to see the nucleotide sequence at the top of the display.

9. Here you can see the actual sequence of human chromosome 11, across roughly 80 bases. The initial zoom brings us into the intron between exons 2 and 3 of the HBB gene. You can explore this zoom level by clicking on the arrows. Eventually you will reach the exons, where the UCSC Genes display can show you the amino acid sequence of the gene.

10. Return to the display of the whole HBB gene. Again, you will see the interval covering all three exons of HBB.
11. Now click the button that says "zoom out 10x." Now instead of looking at roughly 1000 bases, you are looking at more than 10,000 — or 10 kilobases. You will be looking at the immediate neighborhood around HBB. Notice to the right of HBB is another gene, HBD. This is δ (delta) globin, which takes the place of β-globin in a small fraction of circulating hemoglobin. You can click on this gene to get more information about it.


Genome browser display zoomed out 10 times from the HBB gene. To the bottom right, you can see the map position of HBD, human δ-globin.

12. Zoom out again. Instead of 10 kilobases, you are now looking at more than 100 kilobases of chromosome 11. Now you will see a string of genes stretching downstream of HBB. First HBD, then HBBP1, HBG1 and HBG2, and HBE1. All of these genes are structurally similar to β-globin. The reason why they are similar is that they all originated by gene duplications during the early evolution of vertebrates. Originally, they were copies of a single sequence, but they became different over time and some of them took on new functions. This area is called the β-globin gene cluster.

13. The gene labeled HBBP1 is a pseudogene. It has a structure similar to a functional gene but does not correspond to a functional gene product. This kind of pseudogene is almost like a fossil within the genome.
14. The γ (gamma) and ε (epsilon) globin proteins are part of variant hemoglobins. Fetal hemoglobin, HbF, is produced before birth and includes two γ instead of two β subunits, making it α₂γ₂. Embryonic hemoglobin produced in the embryonic yolk sac includes ε subunits along with ζ (zeta) subunits instead of α.

If you have time at this station, enter "HBA1" in the genome search box. This is the α-globin gene found in HbA.

1. On which chromosome is α-globin? Is it inherited together with β-globin?
2. Zoom out on this region. You will find the other genes in the α-globin gene cluster. What are they?
3. What would you hypothesize about the origin of these genes?

Tall parents tend to have tall children.

That's a simple generalization, not an absolute statement. You may be a short person with two tall parents. If you know many families, you'll probably know someone who is an exception to the rule. Two short parents may have a very tall daughter, and two siblings may be very different heights.

Still, if we look at many families we will find that the stature of the parents lets us make some fair predictions about the statures of their children. We can look at data to quantify just how parent and offspring heights are related.

For example, here is a plot of the statures of students in my Anthropology 105 class in 2010, compared to the mean of their mothers' and fathers' statures. The average of mother and father's heights are the midparent stature.

Young men in this class have a taller average stature than young women. The picture separates men and women, and both taller sons and daughters tend to come from taller parents.

We can do a bit better than this to quantify the relationship of the parents' and sons' and daughters' statures: We can put lines on the graph to show how the sons' and daughters' heights tend to increase with the midparent stature:

Each of these lines is called a linear regression between midparent stature and offspring stature. The linear regression is the line that has the smallest squared distance from all of the points, added together.

The squared distance is special. In statistics, the average squared distance from all points to the mean is called the variance. When we consider a trait like stature, there are many possible biological causes that can contribute to individuals being taller or shorter than the average. In statistical terms, these causes are all factors that contribute to the variance of stature.

In the chart above, the linear regression represents the amount of the variance of the stature of the offspring that was contributed by the variance of their midparent statures. Parent statures can predict offspring statures and the linear regression is the prediction.

It's not a perfect prediction. Take a look at the midparent value of 160 cm. When the midparent average is 160 cm, the regressions predict that daughters will be 156 cm and sons will be 168 cm. Out of Anthropology 105 students last year, two men had parents with an average of 160 cm, and both of them were very close to 168 cm in height — a good prediction! But the two women with parents this stature have very different heights. One is only 148 cm, the other 162, both more than 2 inches from the predicted value, in different directions. The regression gives the best prediction we can make from the parents, but there is obviously a lot of variation that can't be predicted in that way.

Let's look more closely at the female students. The following chart adds together females from several years of Anthropology 105, with their midparent statures.

The slope of the regression across these 300 women is 0.72. That means that roughly 72 percent of the variance of the students' stature can be attributed to variance in their midparent stature.

This regression is special in genetics. Daughters resemble their parents because they inherit genes from them. The regression between the midparent and daughters' statures gives us a way to estimate the effects of those genes. In fact, the proportion of variance in a trait that can be explained by genes is the same as the slope of the regression. Geneticists call this proportion the heritability of stature. In my Anthropology 105 classes over the last few years, we would estimate the heritability of stature as 0.72, or 72%.

Again, there are exceptions. Sometimes parents give other things to their children besides genes. The right foods, the right resources can make a difference to growth and development. And some genes can have unexpected effects. Most obviously, some genes make sons a lot taller than daughters, which is why we've considered the two sexes separately.

The heritability of a trait is a powerful concept. It's important to understand some of its strengths and limits:

1. Heritability refers to a population. A female in my Anthropology 105 class may be taller or shorter than her parents. We can't predict 72% of that student's stature; instead, 72% of the variance in the students can be explained by the variance among their parents.
2. Traits with higher heritability have a lower influence from the environment. Traits that are highly influenced by the environment have a lower heritability.
3. The response of a population to selection on a trait is determined by the heritability.
4. Geneticists can look at other relatives besides parents to estimate heritability. Some of the strongest estimates come from comparing identical twins (who have the same genes) to fraternal twins (who share on average half their genes).
5. Estimating heritability doesn't require us to know anything about the actual genes themselves.

The last point is very important. We can quantify the influence of genes without knowing anything about which genes even affect a trait. Francis Galton invented the parent-offspring method of estimating heritability, more than twenty years before the word "gene" was coined. Remembering this helps to remind us that the concept of heritability is limited. It is not a guide to how genes work, it is a simple scale of which traits have a stronger or weaker genetic influence.

Because it is a proportion, heritability varies only between zero and one. A trait with zero heritability is one for which none of the variance can be explained by the parents' variance.

Heritability may be very low because the individuals in the population have little genetic variability. For example, an orchard of apple trees may consist of genetically identical individuals that are clones of a single parent tree. The apples (hopefully) all taste the same. But the trees may be very different in height, branch form, and the number of apples. These traits may be strongly influenced both by the environments of individual trees and by chance. By contrast, wild populations of oak trees are not made up of clones. The heights of individual trees are still strongly influenced by environments, but they may also be influenced by differences in genes.