genetics - Smallest viable reproducing population

The conservation biology literature has a great deal of information, particularly with reference to developing species survival plans (e.g., Traill et al. [2007] report a minimum effective population size of ~4,000 will give a 99% persistence probability of 40 generations).

Because the question specifically mentions human populations, I'll focus my answer on the genetics of small human populations, though considerably less information is available.

Hamerton et al. (1965; Nature 206:1232-1234) studied chromosome abnormalities in 201 individuals from a total population size of 268 from the small island of Tristan da Cunha. These authors report increasing chromosome abnormalities (aneuploidy; hypo- or hyperdiploidy) with age and suggest that it may result in decreased mitotic efficiency. This population is thought to have developed from a founder population of only 15. According to Mantle and Pepys (2006; Clin Exp Allergy 4:161-170) approximately two or three of the original settlers were asthmatic, which has led to a very high prevalence (32%) in the current population.

Kaessmann et al. (2002; Am J Hum Genet 70:673-685) present a more modern study of linkage disequilibrium in two small human populations (Evenki and Saami; ~58,000 and ~60,000 population sizes, respectively) compared to two large populations (Finns and Swedes; ~5 and ~9 million). The authors find significant LD in 60% of the Evenki population and 48% of Saami, but only 29% in Finns and Swedes.

Lieberman et al. (2007; Nature 445:727-731) discuss the potential for human kin detection to avoid inbreeding. Such mechanisms have been found in other species, "from social amoebas, social insects and shrimp, to birds, aphids, plants, rodents and primates." Lieberman et al. propose mechanisms contributing to sibling detection in humans, including "maternal perinatal association" and "coresidence duration." Beyond these behavioral cues, the authors also suggest physiological cues such as major histocompatability complex as playing a role.

evolution - When did vision evolve for the first time?

I'll address the question in the title "At which time did sight evolve for the first time?" by assuming that by the evolution of vision, we mean the evolution of the eye.

Molluscs are an excellent phylum to investigate this question because they exhibit a wide range of eye designs and levels of complexity.

At the most basic level, limpets such as Patella exhibit small patches of photoreceptor cells lying in a relatively flat configuration. Slightly more advanced is Pleurotomaria which has photoreceptors and pigmentation cells held in an eyecup. We then have the pinhole camera style eye as seen in Nautilus (see this post), and more complex eyes with a cornea, retina, and lense such as those seen in squid (e.g. Loligo).

Assuming that "a patch of photoreceptors" in an animal counts as an eye, then we should probably looking for marine invertebrates. The problem here is that if they had only soft body parts we might struggle to identify the oldest examples in sediments.

One candidate for the "earliest eye" might be urbilatarians - the hypothesized last common ancestor of the clade bilatarians - which probably evolved at the end of the Ediacaran period (~555 Myr). An example would be Kimberella (described here) which might or might not have been a mollusc and might or might not have had photoreceptors!

(credit : wikipedia)

bioinformatics - Is there a tool to find the action of an enzyme in a metabolic pathway?

I think the KEGG pathway database may be of some use to you.

Link is here: http://www.genome.jp/kegg/pathway.html

This a database of manually drawn pathway maps, I have used the site myself and it is very useful in determining if your enzyme is in a pathway and where it lies in it. This is assuming though, your enzyme is in the database and has been mapped.

food - How Does Green Tea Increase Metabolism?

According to the article "Green Tea Supplementation Affects Body Weight, Lipids, and Lipid Peroxidation in Obese Subjects with Metabolic Syndrome", Green tea increases metabolism and fat loss:

Green tea beverage consumption (4 cups/d) or extract supplementation
(2 capsules/d) for 8 weeks significantly decreased body weight and
BMI. Green tea beverage further lowered lipid peroxidation versus age-
and gender-matched controls, suggesting the role of green tea
flavonoids in improving features of metabolic syndrome in obese
patients.

Is there any information available concerning the mechanism of that metabolic increase?

bioinformatics - What's the use of DNA sequencing results?

It's just a "string" where nucleotides encode something but I have no idea what they encode specifically.

It sounds like you are describing a computer program, represented by a string of bytes on the hard drive.

Unfortunately, the analogy breaks down very quickly because DNA is vastly more complex and a lot of aspects are still poorly understood.

But the basis is the same: a string of symbols encodes information. In the case of DNA, different parts encode different things in a different manner.

The elephant in the room are of course coding sequences: stretches of DNA, contained in so-called “genes” – which code for proteins and other stuff.

Coding sequences use a fairly simple encoding schema that’s known as the genetic code, decoded in 1961. The genetic code has the nice property of being (almost) universal across all species, and easy enough for a child to understand:

Three consecutive DNA base pairs form a codon. Each codon stands for one amino acid (except for a special “stop codon”). Amino acids form so-called polypeptide chains – proteins. There are codon tables, just as you have manuals for assembly mnemonics in computing:

Unfortunately, it’s not trivial to know where genes are on the genome. Just by eyeballing the sequence there is nothing to distinguish one stretch of DNA from its surrounding. But there are certain recognisable stretches of DNA (“motifs”) which we can use to locate genes and other interesting regions.

Grossly simplified, a gene is preceded by a promoter region which is highly conserved between species (but gene-specific). Once you’ve identified one species’ promoter, you know it for other species. Furthermore, all promoters share highly similar elements, for instance the TATA box – literally the occurrence of “TATA” in the genome.

Of course, just looking for occurrences of “TATA” would yield vastly more spurious hits than actual promoters but combined with other information you get a gene model – a statistical machine which can tell you with high confidence where on a genome the genes are located.

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Once you have found the genes in a sequence which you can trivially translate to amino acid sequences, you can try to form inferences about the function of the proteins (a protein’s function is an almost-direct consequence of its sequence). Unfortunately, discovering the function of a protein from its sequence alone isn’t possible but we do know the functions of many proteins.

When we now look at a genome and find a mutation in a protein-coding gene we can infer that the function of this protein is probably modified. Most mutations are so-called deleterious mutations (e.g. by deleting a single nucleotide you get a frame shift in the codons, and all the subsequent codons no longer make sense), meaning that they destroy the protein’s function.

Other, much rarer, mutations modify the protein’s function, making it more or less efficient, or giving it another function altogether.

In the simplest case (but these are rare), a single such mutation can explain a complex phenotype. This is known as a Mendelian trait and can be used to explain a phenotypes such as eye colour, but also hereditary diseases.

Usually, though, it is merely one of many adjusting screws which skew your susceptibility to a certain phenotype in one direction. For instance, you might be slightly more susceptible to breast cancer or diabetes.

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This is one use of the DNA sequence, there are many more; in the last decade, we have realised that regulation of gene activity plays a much larger role than anticipated, and most research today looks at regulatory patterns on the DNA level. This is also done with sequence data, but there doesn’t appear to be a simple schema analogous to the genetic code to understand regulation. Instead, it’s a complex interplay of many completely unrelated mechanisms.

biochemistry - Structure of RAP Antibodies (Specifically RAP-5)

[EDIT] - Have just found not one but two papers that address my structure problem. However they concern RAP-1A, so I guess my question is now what is the difference in structure and function of RAP-1A and RAP-5? Does anyone know of X-ray structure analysis being used to examine RAP-5?

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original question

I'm a University Physics student writing a mock review article on what to me feels like a very 'un-physicsy' antibody - RAP-5.

Although my knowledge of Biology is pretty poor, research is going quite well. I've found a lot of papers from the 80s talking about conducting immunohisto(/cyto)chemistry experiments, most of them finding that RAP-5 can be used to determine whether a cell has the ras in it, so they are able to measure the percentage of cells that are neoplastic (I believe this means cancerous) and contain ras and the percentage of cells which are normal and contain ras. (the ras-gene being a proto-oncogene which on mutation can result in permanently switched on ras proteins (p21?), which results in proliferation of cells and therefore can cause tumors). This is all very nice but on first glance immunohistochemistry doesn't seem to involve a huge amount of physics (for my bio-physics assignment), apart from using an optical microscope.

I was hoping to be able focus a section of my article on the physical techniques involved in determining the structure of RAP-5. Although there seems to be plenty of literature on uses of RAP-5, I am struggling to find anything on the details on why it is able to be used in such experiments. In other words, I presume that its function is to bind on to an epitode specific to the ras protein (amino acids 10 -17 have popped up a few times) but I don't know if there is any imaging one can do to have a look at the structure and conclude 'yes this is why it binds to ras proteins and not to others'. Is there a technique that is likely to have been used to examine the structure of RAP-5? Is it's tertiary structure likely to be 'Y' shaped like other antibodies? Does it differ in structure from RAP1-4? (this book informs me that RAP1 and RAP2 have 60% sequence identity, but most sources seem to leave out RAP3-to-5, some evening telling me that the RAP family consists of RAP1A/B, RAP2A/B/C and no others!).

Also, if RAP-5 is an antibody, does this mean that it is produced in the body and gets involved in the ras protein signal pathway in order to reduce too much ras expression? (am I right in saying the amount of expression is the amount of protein the ras-gene is producing?) or is it only synthetically produced and used in experiments to measure the amount and location of ras proteins?

Also there seems to be little differentiation between the differences in the functions of each RAP. RAP-5 seems to be used quite a bit in experiments involving Ha-ras - but not exclusively. Do the different RAPs bind to different variants of ras? Ha-ras being the one unique to RAP-5.