Posts Tagged ‘genomics’
understanding genomics 3: SNPs and other esoterica
Canto: So SNPs are pretty essential to modern genomics I believe, so why, and what are they? I know that they’re ‘single nucleotide polymorphisms’ and that nucleotides are A, C, G, T and U, each of which have a slightly different structure. They’re all based on sugar structures – ribose in the case of RNA and deoxyribose in the case of DNA – attached to a phosphate group and a nitrogenous base. Here’s a diagram of thymine (T) filched from the USA’s National Human Genome Research Institute:
So that’s a nucleotide, one of the building blocks of DNA and RNA, but the real problem, for me anyway, is the connection between single and polymorphic, if there is one. I know that poly means many and that morphology is about shape and size and such….
Jacinta: You can only get so far with interrogating the words themselves. An SNP is a genetic variation in a single nucleotide between one person’s genome and another (I think). But there are many of these variations, which is where the ‘poly’ comes in. I’ll quote this from a NIH website, and then try to make sense of it:
SNPs occur normally throughout a person’s DNA. They occur almost once in every 1,000 nucleotides on average, which means there are roughly 4 to 5 million SNPs in a person’s genome. These variations occur in many individuals; to be classified as a SNP, a variant is found in at least 1 percent of the population. Scientists have found more than 600 million SNPs in populations around the world.
Canto: So they’re called ‘variants’ because they vary from the ‘normal’ pattern in 1% or more of those whose genomes are mapped? So there’s such a thing as a ‘normal’ human genome, but perhaps everyone differs from that normal pattern due to different SNPs? And why is 1% the cut-off? Isn’t that a bit arbitrary? Also, it says that these variations occur in many individuals, which sounds a bit vague. Does this mean that there are many individuals where they don’t occur at all? I mean, what is a normal human genome, if there are so many variants? Is it just some kind of aggregated value?
Jacinta: Uhh, maybe. And note – but I’m not sure if this is relevant to your question – that these SNPs mostly occur in non-coding DNA, where they won’t be affecting the phenotype and its general functioning, though it seems to depend on how close they are to coding regions. Anyway, we’re just scratching the surface here. Look at this diagram, from Wikipedia.
As you can see, there are synonymous and non-synonymous SNPs. Synonymous with what, you might ask?
Canto: As a language teacher I know what a synonym is, obviously. My guess is that a synonymous SNP is associated with, ‘synonymous’ with, some kind of malfunction or defect, or maybe different function or effect. A ‘missence’, as the diagram suggests.
Jacinta: No, it’s the non-synonymous SNPs that cause the problems, because coding DNA generally leads to effective function, that’s what it’s all about. If the SNP is synonymous then it works toward proper functioning, perhaps by a different pathway, or it just doesn’t affect the pathway.
Canto: What I’m learning about genetics/genomics is that the more I delve into the subject, the more there is to learn, and yet I don’t really want to specialise, I want to know a bit of everything. I’ve just learned, for example, that it’s not just a divide between coding and non-coding DNA, because a mutation near a coding region can have effects, deleterious or otherwise, I think.
Jacinta: I don’t know about that, but I’m learning some interesting random facts, for example that there appears to be more C-G base pairings in coding DNA than T-A. Just to get it in our heads, cytosine (a pyrimidine) always pairs with guanine (a purine), and the other pyrimidine, thymine, always pairs with adenine. Always purines with pyrimidines, and purines are the larger molecules, with a two-ring structure, rather than one for pyrimidines. Note the structure of thymine, above. Anyway, back to SNPs, which we’re interested in mainly for what they might tell us about earlier populations. I’ve just glanced through a 2020 research article – generally way to technical for lay persons or dilettantes like us, titled ‘Genome-wide SNP typing of ancient DNA: Determination of hair and eye color of Bronze Age humans from their skeletal remains’. I did get some useful info from it though. The researchers compared the SNP method with ‘single base extension (SBE) typing’, and what they found was interesting enough:
The DNA samples were extracted from the skeletal remains of 59 human individuals dating back to the Late Bronze Age. The 3,000 years old bones had been discovered in the Lichtenstein Cave in Lower Saxony, Germany.
It seems that this was a kind of proof-of-concept piece of research, and they were able to obtain good to excellent results from two thirds of the skeletal samples:
With the applied technique, it was for the first time possible to get information about major phenotypic traits—eye and hair color—of an entire prehistoric population. The range of traits, varying from blonde to brown hair and blue to green-hazel eye colors for the majority of individuals is a plausible result for a Central European population.
Canto: Yes, that’s the exciting stuff – true it’s only going back 3000 years, and you could say that there were no surprises in the findings – but it brings the past back to life in such a vivid way… what can I say?
Jacinta: So you don’t want to know about haplotypes, and homozygous and heterozygous alleles? What’s wrong with you?
Canto: Okay, a haplotype – haven’t we gone through this? – a haplotype is a set of variants, or polymorphisms, along a single chromosome, involving one or more genes, that tend to stick together, inheritance-wise. We know that homozygous inheritance means inheritance from both parents whereas heterozygous means that you have a different genetic marker from each parent. A genetic marker is any ‘DNA sequence with a known location on a chromosome’. They may offer clues to inherited traits, such as diseases. All of this comes from the USA’s National Human Genome Research Institute, and I think I mostly understand it.
Jacinta: So SNPs can have all sorts of uses, regarding the present and the past, and tracing the present into the past, as with disease gene mapping. Their abundance within the genome has made them the go-to marker in bioinformatics. My guess, though, is we’ll never get to fully understand them without actually working with them. I mean, we can go through ScienceDirect, and jump from underlined term to underlined term (e.g. linkage disequilibrium, QTL mapping, PCR assays, point mutations and the like), but we’ll start to forget it all from the moment we have aha moments, because for us dilettantes, locked out of labs due to dumbness, shyness, laziness, poverty-ness etc, it’s all just book-larnin, sans even books. I suppose we just have to be grateful that we’ve, or they’ve, developed the technology to collect and analyse SNPs, to create libraries of them…
Canto: It seems like, as with so many fields, we’re at what Deutsch called ‘the beginning of infinity’ – but then didn’t they think that at the advent of string theory?
Jacinta: But we know this isn’t theory, this is about results. Tools producing results. Tools within the body, or rather natural phenomena made into tools by human ingenuity, like circles made into wheels, cubes into containers, triangles into struts. And we’re likely to get more and more out of DNA in the future. I recently learned about the petrous bone, though of course researchers have known about it for some years – it’s about the hardest part of the skull, down somewhere near the foramen magnum I think, and its density has, it seems, been a preservative for DNA – generally better than teeth. So that means more analysis of fossil collections. As David Reich puts it, technologies for analysing ancient DNA have created an explosion of information to rival the invention of the microscope/telescope a few hundred years ago.
Canto: Yes, some of the developments he mentions are next-generation sequencing (which has vastly reduced sequencing costs), more efficient DNA extraction methods, improvements in separating human from microbial DNA, and again the use of the petrous bone for extraction – a bone which tends to remain intact longer than others.
Jacinta: Okay, so we might continue to blunder on in trying to make sense of this genomics stuff, or maybe not. Enough for now.
References
https://www.genome.gov/genetics-glossary/Nucleotide
https://medlineplus.gov/genetics/understanding/genomicresearch/snp/
https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/point-mutation
https://en.wikipedia.org/wiki/Coding_region
https://onlinelibrary.wiley.com/doi/full/10.1002/ajpa.23996
understanding genomics 2: socio-sexual inequities and bonobos!
1 in 200 Men are Direct Descendants of Genghis Khan – Answers in Genomics!
Jacinta: So this blog piece is a bit of a change of pace from the science we’re obviously having trouble with – and I should mention that we’ve started watching the 11-part ‘Introduction to genomics’ videos online to help us with the basics – but what we’ve read in Who we are and how we got here and other texts is providing further evidence of a violent past that reflects an ancestry more associated with chimp-like behaviour, much exacerbated by the deadly weapons we developed along the way, than the bonobo togetherness that my endless optimism sees signs of in that part of the world that is increasingly empowering the female sex.
Canto: Yes, that in itself is a long story of gradual release from the masculinist Catholic hegemony of the medieval world, with its witch-hunts and its general suppression of female power and influence…
Jacinta: Going much further back in fact to the ancient Greeks and, for example, Homer’s Odyssey, and the treatment of women therein, as explored on this site years ago (referenced below).
Canto: Yes, this general improvement in the treatment of women, and of each other – the end of witch-hunts (I mean real ones) and public executions and torturings and so on – at least in English-speaking and Western European nations, has been highlighted in Pinker’s The better angels of our nature and other analyses. But we still have the Chinese Testosterone Party, the masculinist horrors of Iran and Afghanistan, and the macho thuggery of little Mr Pudding and his acolytes, to name but a few. The humano-bonobo world is still a long way off.
Jacinta: Yes the Ukrainian horror, getting all the airplay here that Mr Putin’s incursions in Chechnya, Syria and Georgia didn’t, reminds us that the horrors of two major European wars and Japan’s macho offensives in the first half of the 20th century haven’t been enough to reform our world – from a human one to a humano-bonobo one. But I doubt that genetic tinkering would do the trick.
Canto: Vegetarianism perhaps? But then, Hitler…
Jacinta: No easy solutions I’m afraid. But there are some who are interested in using genomics to highlight just how un-bonobo-like our past has been. Or rather, it’s not so much an interest, it’s more like telling the gruesome story that genomic data is revealing to them. In Neil Oliver’s History of Scotland, for example, he recounts how genomic data reveals that the Pictish men of the Orkneys and the northern tip of Scotland were almost completely replaced by men from Northern Europe, the Vikings, in the eighth and ninth centuries CE, while the female line remained largely Pictish. Slaughter, combined with probable rape, being the best explanation. Reading this reminded me of the chimpanzee war of the seventies in Tanzania, which admittedly was more of a civil war, and apparently less one-sided than the Viking invasion of the Orkneys, or the European invasion of the Americas, or the British invasion of Australia, but in some ways it was similar – an attempt, if not entirely conscious, to replace one population with another, and to the victor, the spoils.
Canto: Well, Reich is fairly circumspect in his book, but he does have a small section towards the end, ‘The genomics of inequality’, from which we may draw pretty clear inferences:
Any attempt to paint a vivid picture of what a human culture was like before the period of written texts needs to be viewed with caution. Nevertheless, ancient DNA have provided evidence that the Yamnaya [a relatively advanced steppe culture that emerged about 5000 years ago] were indeed a society in which power was concentrated among a small number of elite males. The Y chromosomes that the Yamnaya carried were nearly all of a few types, which shows that a limited number of males must have been extraordinarily successful in spreading their genes. In contrast, in their mitochondrial DNA, the Yamnaya had more diverse sequences.
and
This Yamnaya expansion also cannot have been entirely friendly, as is clear from the fact that the proportion of Y chromosomes of steppe origin in both western Europe and in India today is much larger than the proportion of steppe ancestry in the rest of the genome.
This is a roundabout or academic way of saying, or ‘suggesting’ (oh dear, I’m becoming an academic) that the Yamnaya forcibly replaced many of the males of earlier populations in those regions and interbred, in one way or another, with the females.
Jacinta: Yes, again very chimp-like, mutatis mutandis. The good thing is that we’re more and more coming to terms with our violent past – and I would love to be able to trace it further back, beyond Homo sapiens, or at least to the earliest H sapiens 100,000 years ago or so.
Canto: Well, I’m thinking that the CHLCA (chimp human last common ancestor) would be a good place to start, but we’ll probably never know what that population was like – was it more chimp-like or bonobo-like in its social (and sexual) behaviour? But there’s a huge difference between that CHLCA and us – just consider brain size.
Jacinta: But that’s a tricky measure – look at H naledi and H floresiensis. Chimps average around 400cc, gorillas 500cc, H naledi has been estimated at anything from 450 to 600cc, and H floresiensis, from the only extant skull, came in at 426cc. And those two hominins are considered relatively modern. Our brain size is about 1300cc. It’s over the place. But forget all these caveats for a moment, I’ve heard that we got our bigger brains courtesy of hunting big game and cooking meat – and the hunting at least strikes me as a macho activity, leading to a hierarchy of the big and strong, and so, alpha males and all the shite that follows…
Canto: Yes, and bonobos have evolved in a more physically restricted but resource-rich environment, and have somehow become less hierarchy-obsessed, though still hierarchical – the sons of the most powerful females apparently have a higher status in the male hierarchy.
Jacinta: Yes all this is important as we strive to establish a humano-bonobo world. In our incredibly diverse human world we have people dying of over-eating in some parts, and of starvation and malnutrition in others. But in the world of relative abundance that you and I live in, mechanisation and other technologies have reduced the need for physical strength, and testosterone levels in males have dropped rapidly in just the last few decades. We’re eating meat more than ever, but in our cities, nobody can hear the victims’ screams. And we don’t have to do the hunting and killing ourselves, so if we want to toughen up we have to do it via gymnasiums and sports, which are no longer gender-exclusive.
Canto: All this has little to do with genomics, but it seems to me that the macho-chimp orientation of early humans since the CHLCA has much to do with increased proliferation, diversity and inter-group competition for resources, especially over the last 20,000 years, or less. The domestication of horses and the invention of the wheel, and sophisticated sea-going vessels would have helped. Different groups advanced at different rates, with some developing better weapons – for hunting and then for warfare, and naturally they hankered for more territory to expand into, to ‘lord over’. Those more advanced groups became more hierarchical, and gaining more territory and ‘winning’ over more people became an end in itself – think of early versions of Genghis Khan and little Mr Pudding.
Jacinta: That’s why, like the female bonobos who gang up on uppity males before they can do too much damage, we need to stick it the Mr Puddings of the world – hit em hard, before they know what hit em.
References
https://www.discovermagazine.com/planet-earth/1-in-200-men-direct-descendants-of-genghis-khan
David Reich, Who we are and how we got here, 2018
understanding genomics 1 – mitochondrial DNA
Canto: So maybe if we got humans to mate with bonobos we’d get a more promising hybrid offspring?
Jacinta: Haha well it’s not that simple, and I don’t mean just physiologically…
Canto: Okay those species wouldn’t be much attracted to each other – though I’ve heard that New Zealanders are very much attracted to sheep, but that just might be fantasy. But seriously, if two species – like bonobos and chimps, can interbreed, why can’t bonobos and humans? And they’d don’t have to canoodle, you can do it like in vitro fertilisation, right?
Jacinto: Well, bonobos and chimps are much more closely related to each other than they are to humans. And if you think bonobo-human hybridisation will somehow create a female-dominant libertarian society, well – it surely ain’t that simple. What we see in bonobo society is a kind of social evolution, not merely a matter of genetics. But having said that, I’m certainly into exploring genetics and genomics more than I’ve done so far.
Canto: Yes, I’ve been trying to educate myself on alleles, haplotypes, autosomal and mitochondrial DNA, homozygotism and heterozygotism (if there are such words), single nucleotide polymorphisms and…. I’m confused.
Jacinta: Well, let’s see if we can make more sense of the science, starting with, or continuing with Who we are and how we got here, which is mostly about ancient DNA but also tells us much about the past by looking at genetic variation within modern populations. Let me quote at length from Reich’s book, a passage about mitochondrial DNA – the DNA in our mitochondria which is somehow passed down only along female lines. I’ve no idea how that happens, but…
The first startling application of genetics to the study of the past involved mitochondrial DNA. This is a tiny proportion of the genome – only approximately 1/200,000th of it – which is passed down from mother to daughter to granddaughter. In 1987, Allan Wilson and his colleagues sequenced a few hundred letters of mitochondrial DNA from diverse people around the world. By comparing the mutations that were different among these sequences, he and his colleagues were able to construct a family tree of maternal relationships. What they found is that the deepest branch of the tree – the branch that left the main trunk earliest – is found today only in people of sub-Saharan African ancestry, suggesting that the ancestors of modern humans lived in Africa. In contrast, all non-Africans today descend from a later branch of the tree.
Canto: Yes, I can well understand the implications of that analysis, but it skates fairly lightly over the science, understandably for a book aimed at the general public. To be clear, they looked at the same stretches of mitochondrial DNA in diverse people, comparing differences – mutations – among them. And in some there were many mutations, suggesting time differences, due to that molecular clock thing. And I suppose those that differed most – from who? – had sub-Saharan ancestry.
Jacinta: Dating back about 160,000 years, according to best current estimates.
Canto: The science still eludes me. First, how does mitochondrial DNA pass only through the female line? We all have mitochondria, after all.
Jacinta: Okay, I’ve suddenly made made myself an expert. It all has to do with the sperm and the egg. One’s much bigger than the other, as you know, because the egg carries nutrients, including mitochondria, the only organelle in your cytoplasm that has its own DNA. Your own little spermatozoa are basically just packages of nuclear DNA, with a tail. Our mitochondrial DNA appears to have evolved separately from our nuclear DNA because mitochondria, or their ancestors, had a separate existence before being engulfed by the ancestors of our somatic or eukaryotic cells, in a theory that’s generally accepted if difficult to prove. It’s called the endosymbiosis theory.
Canto: So mitochondria probably had a separate, prokaryotic existence?
Jacinta: Most likely, which could take us to the development, the ‘leap’ if you like, of prokaryotic life into the eukaryotic, but we won’t go there. Interestingly, they’ve found that some species have mitochondrion-related organelles with no genome, and our own and other mammalian mitochondria are full of proteins – some 1500 different types – that are coded for by nuclear rather than mitochondrial DNA. Our mitochondrial DNA only codes for 13 different types of protein. It may be that there’s an evolutionary process going on that’s transferring all of our mitochondrial DNA to the nucleus, or there might be an evolutionary reason for why we’re retaining a tiny proportion of coding DNA in the mitochondria.
Canto: So – we’ve explained why mitochondrial DNA follows the female line, next I’d like to know how we trace it back 160,000 years, and can place the soi-disant mitochondrial Eve in sub-Saharan Africa.
Jacinta: Well the term’s a bit Judeo-Christian (there’s also a Y-chromosomal Adam), but she’s the matrilineal most recent common ancestor (mt-MRCA, and ‘Adam’ is designated Y-MRCA).
Canto: But both of these characters had parents and grandparents – who would be somehow just as common in their ancestry but less recent? I want to know more.
Jacinta: To quote Wikipedia…
… she is defined as the most recent woman from whom all living humans descend in an unbroken line purely through their mothers and through the mothers of those mothers, back until all lines converge on one woman.
… but I’m not sure if I understand that convergence. It clearly doesn’t refer to the first female H sapiens, it refers to cell lines, haplogroups and convergence in Africa. One of the cell lines used to pinpoint this convergence was HeLa, the very first and most commonly used cell line for a multiplicity of purposes…
Canto: That’s the Henrietta Lacks cell line! We read The Immortal Life of Henrietta Lacks! What a story!
Jacinta: Indeed. She would be proud, if she only knew… So, after obtaining data from HeLa and another cell line, that of an !Kung woman from Southern Africa, as well as from 145 women from a variety of populations:
The published conclusion was that all current human mtDNA originated from a single population from Africa, at the time dated to between 140,000 and 200,000 years ago.
Canto: So mt-MRCA is really a single population rather than a single person?
Jacinta: Yeah, maybe sorta, but don’t quote me. The Wikipedia article on this gives the impression that it’s been sheeted home to a single person, but it’s vague on the details. Given the way creationists leap on these things, I wish it was made more clear. Anyway the original analysis from the 1980s seems to be still robust as to the time-frame. The key is to work out when all female lineages converge, given varied mutation rates. So, I’m going to quote at length from the Wikipedia article on mt-MRCA, and try to translate it into Jacinta-speak.
Branches are identified by one or more unique markers which give a mitochondrial “DNA signature” or “haplotype” (e.g. the CRS [Cambridge Reference Sequence] is a haplotype). Each marker is a DNA base-pair that has resulted from an SNP [single nucleotide polymorphism] mutation. Scientists sort mitochondrial DNA results into more or less related groups, with more or less recent common ancestors. This leads to the construction of a DNA family tree where the branches are in biological terms clades, and the common ancestors such as Mitochondrial Eve sit at branching points in this tree. Major branches are said to define a haplogroup (e.g. CRS belongs to haplogroup H), and large branches containing several haplogroups are called “macro-haplogroups”.
So let’s explain some terms. A genetic marker is simply a DNA sequence with a known location on a chromosome. A haplotype or haploid genotype is, as the haploid term suggests, inherited from one rather than both parents – in this case a set of alleles inherited together. SNPs or ‘snips’ are differences of a single nucleotide – e.g the exchange of a cytosine (C) with a thymine (T). As to the rest of the above paragraph, I’m not so sure. As to haplogroups, another lengthy quote makes it fairly clear:
A haplogroup is…. a group of similar haplotypes that share a common ancestor with a single-nucleotide polymorphism mutation.More specifically, a haplogroup is a combination of alleles at different chromosomal regions that are closely linked and that tend to be inherited together. As a haplogroup consists of similar haplotypes, it is usually possible to predict a haplogroup from haplotypes. Haplogroups pertain to a single line of descent. As such, membership of a haplogroup, by any individual, relies on a relatively small proportion of the genetic material possessed by that individual.
Canto: Anyway, getting back to mt-MRCA, obviously not as memorable a term as mitochondrial Eve, it seems to be more a concept than a person, if only we could get people to understand that. If you want to go back to the first individual, it would be the first mitochondrion that managed to synthesise with a eukaryotic cell, or vice versa. From the human perspective, mt-MRCA can be best conceptualised as the peak of a pyramid from which all… but then she still had parents, and presumably aunts and uncles…. It just does my head in.
References
https://www.genome.gov/genetics-glossary/Mitochondrial-DNA
https://en.wikipedia.org/wiki/Mitochondrial_Eve
https://en.wikipedia.org/wiki/Haplogroup
Did bonobos do it with chimps? Well, duh
bonobos or chimps? Or both? Or neither? What’s in a name…?
Canto: So we’ve been learning than we did it with Neanderthals, and that Neanderthals did it with Denisovans, and I remember hearing an anthropologist or palaeontologist saying that it’s likely that our split with our last common ancestor with chimps and bonobos – they call it the CHLCA (chimp-human last common ancestor, eliminating bonobos altogether, sigh) – wasn’t necessarily a clean break, which surely makes sense.
Jacinta: Well, yes, as we’ve read, the split was caused by the relatively sudden creation of the Congo River, but the word ‘relatively’, is, well, relative. So this raises the question of speciation in general. Think of those Galapagos finches that so intrigued Darwin. All about differently-shaped beaks, but it didn’t happen overnight.
Canto: Right, so here’s what a website with the rather all-encompassing title “Science” says about our topic:
Tens of thousands of years ago, modern humans slept around with Neandertals and swapped some genes. Now, it turns out one of our closest living relatives, chimpanzees, also dallied with another species. New research reveals that chimps mixed it up with bonobos at least twice during the 2 million years since these great apes started evolving their own identities. Although it’s not yet clear whether the acquired genes were ultimately beneficial or harmful, the finding strengthens the idea that such cross-species mating played an important role in the evolution of the great apes.
Jacinta: Interestingly this Congo River separation which led to a completely different species was repeated by other separations which led to four sub-species of chimps. Which leads me to wonder – what’s the difference between a new species and a sub-species? Why are bonobos ‘deserving’ of being called a different species?
Canto: Well the Science article has some fascinating further information. This was the work of Christina Hvilsom and colleagues, described as ‘conservation geneticists’. They were using any genetic differences they could find to work out where particular chimps were being caught or hunted. But, since the interbreeding of humans and Neanderthals, proven by DNA, had hit the headlines, Hvilsom wondered about the DNA of chimps. So, using the same methods that uncovered Neanderthal in humans –
she and her colleagues determined that 1% of the central chimpanzee’s genome is bonobo DNA. The genetic analysis indicates that this inbreeding happened during two time periods: 1.5 million years ago bonobo ancestors mixed with the ancestor of the eastern and central chimps. Then, just 200,000 years ago, central chimps got another boost of bonobo genes, the team reports today in Science. In contrast, the western chimp subspecies has no bonobo DNA, the researchers note, suggesting that only those chimps living close to the Congo River entertained bonobo consorts.
Jacinta: What this highlights, more than anything to me, is the importance and excitement of genetic and genomic analyses. Not that we’re experts on the topic, but it has clearly revolutionised the science of evolution, complicating it in quite exciting ways. Think again of those Galapogos finches. Separation, some interbreeding, more separation, less interbreeding, but with a few kinks along the way.
Canto: And we’re just beginning our play with genetics and genomics. There’s surely a lot more to come. Ah, to live forever…
Jacinta: So how did they know some inbreeding occurred? Can we understand the science of this without torturing ourselves?
Canto: David Reich’s book Who we are and how we got here tells the story of interbreeding between human populations, and how population genetics has revolutionised our understanding of the subject. With dread, I’ll try to explain the science behind it. First, the Science article quoted above mentions a split between bonobos and chimps 2 million years ago. Others I’ve noted go back only about a million years – for example a Cambridge University video referenced below. The inference, to me, is that there was a gradual separation over a fair amount of time, as aforementioned. I mean, how long does it take to create a major river? Now, I can’t get hold of the data on chimp-bonobo interbreeding in particular, so I’ll try to describe how geneticists detect interbreeding in general.
I’ll look at the human genome, and I’ll start at the beginning – a very good place to start. This largely comes from Who we are and how we got here, and the following quotes come from that book. The human genome consists of a double chain of 3 billion nucleobases, adenine, cytosine, guanine and thymine. That’s 6 billion bases (often called letters – A, C, G and T) in all. Genes are small sections of this base chain (called DNA), typically a thousand or so letters long. They’re templates or codes for building proteins of many and varied types for doing many different kinds of work, although there are segments in between made up of non-coding DNA.
Researchers have been able to ‘read’ these letters via machinery that creates chemical reactions to specific DNA sequences:
The reactions emit a different colour for each of the letters A, C, G and T, so that the sequence of letters can be scanned into a computer by a camera.
What anthropologists want to focus on are mutations – random errors in the copying process, which tend to occur at a rate of about one in every thousand letters. So, about 3 million differences, or mutations, per genome (3 billion genes, coding or non-coding). But genomes change over time due to these mutations and each individual’s genome is unique. The number of differences between two individuals’ genomes tells us something about their relatedness. The more differences, the less related. And there’s also a more or less constant rate of mutations:
So the density of differences provides a biological stopwatch, a record of how long it has been since key events occurred in the past.
As Reich recounts, it was the analysis of mitochondrial DNA, the tiny proportion of the genome that descends entirely down the maternal line, that became a corner-stone of the out-of-Africa understanding of human origins, which had been competing with the multi-regional hypothesis for decades. ‘Mitochondrial Eve’ – a rather ‘western’ moniker considering that the Adam and Eve myth is only one of a multitude of origin stories – lived in Botswana in Southern Africa about 160,000 to 200,000 years ago, given the variability of the genomic ‘clock’ – the mutation rate.
So, what does this have to do with chimps and bonobos? Well, The exact detail of how Hvilsom et al proved that their (slightly) more recent interbreeding events occurred is hidden behind a paywall, and you could say I’m a cheapskate but the reality is I’m quite poor, trying to bring up seven kids and a few dozen grandkids in a home not much bigger than a toilet, so… but truthfully I’m just getting by, and I just want to know in general the techniques used.
First, they have to find ancient specimens, I think. But, in a video referenced below, they raised the question – Can we ‘excavate’ ancient DNA from modern specimens? We’ve learned that many modern humans have a certain percentage of Neanderthal DNA, say around 2%, but each person’s 2% may be different. Aggregating those different segments can, if we analyse the genomes of enough humans, create a whole Neanderthal genome, though not one of any Neanderthal who ever lived! At least that’s how I’m reading it, in my dilettantish way. So what exactly does this tell us? I’m not at all sure – it’s a relatively new research area, and completely new to me.
The presenter of this video uses the heading, at least at the beginning of his talk, ‘A little Archaic introgression goes a long way’. So now I need to know what introgression means. A quick look-up tells me it’s:
‘the transfer of genetic information from one species to another as a result of hybridization between them and repeated backcrossing‘.
I’ve bolded two key words here. Hybridisation, in mammals, is ‘breeding between two distinct taxonomic units’. Note that the term species isn’t used, presumably because it has long been a questionable or loaded concept – life just seems too complex for such hard and fast divisions. Backcrossing seems self-explanatory. Without looking it up, I’d guess it’s just what we’ve been learning about. Canoodling after speciation should’ve ruled canoodling out.
But, looking it up – not so! It’s apparently not something happening in the real world, something like backsliding. But then… Here’s how Wikipedia puts it:
Backcrossing may be deliberately employed in animals to transfer a desirable trait in an animal of inferior genetic background to an animal of preferable genetic background.
This is unclear, to say the least. How could an animal, even a human, deliberately do this? We could do it to other animals, or try it, based on phenotypes. We’ve been doing that for centuries. What follows makes it more or less clear that this is about human experimentation with other animals, though.
Anyway, I’m going well off-topic here. What I wanted to do is try to understand the proof of, or evidence for, bonobo-chimp interbreeding. I accept that it happened, well after the split between these two very similar-looking species. What could be less surprising? Along the way I’ve been reminded inter alia, of homozygous and heterozygous alleles, but I’ve been frustrated that straightforward information isn’t being made available to the general public, aka myself. I’ll pursue this further in later posts.
Jacinta: What a mess. Phenotype isn’t everything my friend. To a bonobo, a chimp probably looks like a neanderthal – a real bonehead… They probably only had sex with them out of pity. ‘Boys, we’ll show you a good time – like you’ve never had before.’
References
https://www.science.org/content/article/chimps-and-bonobos-had-flings-and-swapped-genes-past
David Reich, Who we are and how we got here, 2018
https://www.newscientist.com/article/2110682-chimps-and-bonobos-interbred-and-exchanged-genes/
exploring genetics – Mendel, alleles and stuff
Canto: So I’d like to know as much as I can about genetics before I die, which might be quite soon, so let’s get started. What’s the difference between genetics and genomics?
Jacinta: Okay, slow down – but I suppose that’s as good a place to start as anywhere. I recently listened to a talk about the human genome project, which was completed around 2003, and the number I heard the guy mention was 3 billion genes, or something. But according to videos and other sources, each human has between 20,000 and 25,000 genes – though I’ve found another FAQ which estimates 30,000. So I gather from this that our genome is the number of genes we might possibly have – in the whole human population? Which raises the question, how do we know that the human genome project has captured or mapped all of them.
Canto: So there’s an individual genome, peculiar to each of us, and a collective genome?
Jacinta: Errr, maybe. We’re 99.9% genetically identical to each other, supposedly. And if this sounds very paradoxical, we need to zoom in on the detail. And with that, I’ve discovered that the 3 billion refers to base pairs, sometimes called ‘units of DNA’. So what’s a base pair? Well, we need to start with the structure of DNA, the genetic molecule. That’s deoxyribonucleic acid, which is made up of basic components called nucleotides. A nucleotide of DNA consists of a sugar molecule, a phosphate group and a nitrogenous base. The bases come in four types – adenine, guanine, thymine, and cytosine (A, T, G and C). The sugar and phosphate groups provide structure, allowing the bases to form a long string of DNA. Bonds form between the bases to create a double strand of DNA – hence base pairs.
Canto: Here’s how the World Health Organisation defines genomics, obviously from a health perspective:
Genomics is the study of the total or part of the genetic or epigenetic sequence information of organisms, and attempts to understand the structure and function of these sequences and of downstream biological products. Genomics in health examines the molecular mechanisms and the interplay of this molecular information and health interventions and environmental factors in disease.
Now you might think that this definition could cover genetics too, and maybe we shouldn’t be too worried about the distinction. Maybe, in general, genomics is about sequences of genes, especially in detailing whole organisms, while genetics is more about individual genes.
Jacinta: Genomics is the much more recent term, first coined in the 1980s, whereas genetics and genes date back to before we knew about DNA as the genetic molecule. Going back to Mendel and all, though I don’t think he used the term, he talked about ‘factors’ or some such.
Canto: So we know that there’s DNA, and there’s also RNA, another building block of life. How old are they, and which came first? And can species replicate without these molecules?
Jacinta: Oh dear – we’ll get there eventually, maybe. Genomics deals with the whole complement of genes in an organism, which we’ve gradually realised is necessary to evaluate, say, how prone that organism is to contracting a disease, or developing some immuno-deficiency, because individual genes often don’t tell us much. And there’s also the matter of dominant and recessive genes. Which takes us to inheritance. All those genes are combined together on chromosomes, of which there are 23 pairs in humans, which we inherit from our parents, 23 chromosomes each.
Canto: Combined together? Can you be more specific?
Jacinta: Okay, a chromosome is a thread-like structure, in which DNA is coiled around structural proteins called histones. Each chromosome has two ‘arms’, flowing from a constriction point called a centromere. These arms are labelled p and q. The p arm is shorter than the q. And these chromosomes contain genes, which may or may not code for proteins. The genes, as mentioned, consist of base pairs, which vary in number from hundreds to millions.
Canto: Okay, so what’s the difference between a gene and an allele?
Jacinta: Well, genes are codes for making proteins – and those proteins affect all sorts of things, to do with taste, smell, hair colour and type, height, and predisposition to various diseases, among many other things. You can call these things ‘traits’, which show up in our phenotype, our physical characteristics. And it should be pointed out that many of these traits are the results of not just one gene but different genes in combination. Now, as mentioned, these genes are in pairs of chromosomes – 23 pairs in humans. Now, say we isolate an area in a chromosome that codes for a particular trait. What about the other chromosome in that pair? Remember, each chromosome comes from a male or female parent, and they are different, genetically – or likely to be. That’s where alleles come in, and it takes us back to Mendel, who found that with pea plants, traits such as colour, or the alleles that carried those traits, could be dominant or recessive. So, for that trait, they could carry two dominant alleles, or two recessive alleles, or one of each. If one or both of those alleles is dominant, the trait will be expressed, but if both are recessive, it won’t be. But as I say, it’s more complicated than that, as traits expressed in phenotypes are generally carried by many genes.
Canto: So alleles are? – how to define them?
Jacinta: Google it mate. Here’s a quickly found definition: “each of two or more alternative forms of a gene that arise by mutation and are found at the same place on a chromosome”. So let’s continue with the work of Mendel. When we find a dominant trait, we use a capital, T. It might be paired with another dominant trait, TT, or with a recessive trait, Tt. On the other hand, both traits might be recessive, tt, and that’s all the combos you have, for single traits. Now, in noting this, and the way that alleles combine, Mendel came up with a ‘law of segregation’. Or rather, he noticed a process, which later became recognised as a law. In fact, he observed three fundamental processes, ‘segregation’, ‘independent assortment’, and ‘dominance’, which we now describe as laws. Now, I’ve used the term ‘trait’ but perhaps I should’ve used the term ‘allele’. So TT combines two dominant alleles. The law of segregation has been stated thus:
During gamete formation, the alleles for each gene segregate from each other such that each gamete formed carries only one allele for each gene.
Canto: Right. Uhhh, what’s a gamete again?
Jacinta: Sex cells, which carry only one copy of each chromosome. They’re created during meiosis, after which we end up with four cells each with only one allele for each gene. So indeed, alleles are segregated during gamete formation.
Canto: Oh dear. I’ll have to brush up on meiosis.
Jacinta: So now we have these segregated alleles, which will be recombined. The law of independent assortment comes next. This also occurs during meiosis. In the fourth or metaphase period of cell division, the chromosomes align themselves on the equatorial plane, also called the metaphase plate. This alignment is random, and that’s the key to the law of independent assortment – ‘genes for different traits assort independently of each other during gamete formation’. But obviously Mendel knew nothing about meiosis, though it was first observed in his lifetime, in sea urchins . Anyway, this law allows for many different combinations of alleles depending on how chromosomes become aligned on the metaphase plate. A dihybrid cross will provide more such combinations.
Canto: A dihybrid cross? Please explain.
Jacinta: Well, a monohybrid cross will be like this – TT x tt. Not much to be assorted there. A dihybrid cross might be like this – TtCc x TtCc, creating four different assortments for each cross. So now to the third law, of dominance. This law simply states that ‘some alleles are dominant while others are recessive. An organism with at least one dominant allele displays the effect irrespective of the presence of the recessive one’. So the phenotype will present the dominant allele regardless of whether it’s double-dominant or single-dominant. Though the terms used are homozygous (TT), or heterozygous (Tt).
Canto: So are we going to look at punnett squares now? I’ve heard of them…
Jacinta: Well it might help. They were named after a bloke called Punnett back in 1905, the early days of Mendelian genetics. They’re neat little tables, that can start to get quite complicated, for determining the genotypes of offspring, when you breed dominant with recessive, heterozygous with homozygous and so on. It’s useful for simple genotypes, but when genotypes are multifactorial, as they often are, other methods are obviously required.
Canto: Okay, that’s more than enough to absorb for now.
Jacinta: I think, since we’ve started with Mendel, we might do a historical account. Or maybe not….
References
https://www.google.com/search?client=safari&rls=en&q=alleles&ie=UTF-8&oe=UTF-8
https://byjus.com/biology/mendel-laws-of-inheritance/
https://www.yourgenome.org/facts/what-is-meiosis
A DNA dialogue 1: the human genome
Canto: I’m often confused when I try to get my head around all the stuff about genes and DNA, and genomes and alleles and chromosomes, and XX and XY, and mitosis and meiosis, and dominant and recessive and so on. I’d like to get clear, if only I could.
Jacinta: That’s a big ask, and of course we’re both in the same boat. So let’s use the magical powers of the internet to find answers. For example, here’s something that confuses me. The Human Genome project, which ended around the year 2000, involved a mapping of the whole human genome, and that includes coding and non-coding genes, and I think it was found to contain 26,000 or so – what? Letters? Genes? Coding genes? Anyway there’s a number of questions there, but they’re not the questions that confuse me. I don’t get that we now, apparently, have worked out the genetic code for all humans, but each of us has different DNA. How, exactly, does our own individual DNA relate to the genome that determines the whole species? Presumably it’s some kind of subset?
Canto: Hmmm. This article from the Smithsonian tells us that the genetic difference between human individuals is very tiny, at around 0.1%. We humans differ from bonobos and chimps, two lineages of apes that separated much more recently, by about 1.2%….
Jacinta: Yes, yes, but how, with this tiny difference between us, are we able to use DNA forensically to identify individuals from a DNA sample?
Canto: Well, perhaps this Smithsonian article provides a clue. It says that the 1.2% difference between us and chimps reflects a particular way of counting. I won’t go into the details here but apparently another way of counting shows a 4-5% difference.
Jacinta: We probably do need to go into the details in the end, but clearly this tiny .1% difference between humans is enough for us to determine the DNA as coming from one individual rather than 7 to 8 billion others. Strangely enough, I can well believe that, given that we can detect gravitational waves and such – obviously using very different technology.
Canto: Yeah the magic of science. So the Human Genome Project was officially completed in April 2003. And here’s an interesting quote from Wikipedia:
The “genome” of any given individual is unique; mapping the “human genome” involved sequencing a small number of individuals and then assembling these together to get a complete sequence for each chromosome. Therefore, the finished human genome is a mosaic, not representing any one individual.
Of course it would have to be a mosaic, but how can it represent the whole human genome when it’s only drawn from a small number? And who were these individuals, how many, and where from?
Jacinta: The Wikipedia article does give more info on this. It tells us that the project isn’t really finished, as we’ve developed techniques and processes for faster and deeper analyses. As to your questions, when the ‘finished’ sequencing was announced, the mosaic was drawn from a small number of anonymous donors, all of European origin.
Canto: But we all originated from Africa anyway, so…
Jacinta: So maybe recent ‘origin’ isn’t so important. Anyway, that first sequencing is now known as the ‘reference genome’, but after that they did sequence the genomes of ‘multiple distinct ethnic groups’, so they’ve been busy. But here are some key findings, to finish off this first post. They found some 22,300 protein-coding genes, as well as a lot of what they used to call junk DNA – now known as non-coding DNA. That number is within the mammalian range for DNA, which no doubt surprised many. Another blow for human specialness? And they also found that there were many more segmental duplications than expected. That’s to say, sections of DNA that are almost identically repeated.We’ll have to explore the significance of this as we go along.
Canto: Yes, that’s enough for starters. Apparently our genome has over 3 billion nucleobase pairs, about which more later no doubt.
References