Tag Archives: genes

Sequencing the Human Genome

On June 26, 2000, U.S. President Bill Clinton, geneticists Francis Collins and Craig Venter, announced the completion of the “first survey” of the entire human genome. The announcement was made in front of a large audience at the White House, which signified the importance of the milestone. Actually, the sequencing of the human genome was not yet complete; the presentation had been arranged as a compromise between two competing parties. On one side, the government-funded Human Genome Project, and on the other side a private company, Celera Genomics.

Collins was the head of the Human Genome Project, Venter represented Celera Genomics. The truce had been arranged to end a race for a complete sequence of the human genome. Over a number of years both groups had made considerable progress and where getting close to the finish line. The joint statement would ensure that both sides would get credit upon completion; all the letters of human DNA would soon be spelled out. Francis Collins ended his talk with the following statement: “I am happy that today, the only race that we are talking about is the human race.”

The Controversy

The Human Genome Project was launched in 1990. The task at hand was enormous. The human DNA code consisted of over 3 billion letters. It was estimated that it would take 50,000 person years of labor, at a cost of $3 billion. Collins compared the project’s scale to going to the moon or splitting the atom. As it turned out, two competing groups would go after the genome. They would differ in both technique and purpose.

Craig Venter

Celera Genomics was using a method of sequencing called shotgun. Criag Venter believed he could speed up the process by ignoring large parts of the genome located between genes. These sections encode for regulating genes, such as on and off switches, and some parts have no known function. Venter would essentially break up the genome, sequence the genes and then try to put the pieces back together.

Perhaps another motivation for the shotgun approach was to map individual genes in the hope to patent genes. Venter informed Collins his intention to seek patents for 300 genes that would serve as targets for drugs to treat diseases. In addition, the question whether the whole genome could be patented was uncharted territory.

Francis Collins

The Human Genome Project’s founding leader was James Watson, one of the co-discoverers of the structure of DNA (the double helix in 1953). Watson had the credentials to get government funding for the project; however, he was outspoken and sometimes that got him in trouble. Watson was replaced by Francis Collins in 1993, which was more cautious and diplomatic, traits that would be needed to steer the project to completion. Collins’ group did not believe that individual genes or the genome should be up for patents. The genome belonged to everyone and should not be privatized for profit. Also, there was concern that Venter’s Shotgun method would reveal an incomplete genome, one that could not be put back together.

Scattered throughout the genome are DNA fingerprints. These are repeating patterns of code that are unique to each individual (except for identical twins), hence the term DNA fingerprints. The Human Genome Project would use DNA fingerprints to break up the task of sequencing. The DNA fingerprints stood out from the random code along the genome; this provided a natural break in which the genome could be divided up, and later put back together. The genome was divided into segments and sent to 16 labs around the world. Once each section was sequenced the genome could be placed back together

The controversy and the race for the genome increased the pace of the sequencing. In the end, both sides would publish papers on a sequenced human genome. On February 15, 2001, The Human Genome Project published their results in the scientific journal, Nature. The next day Celera published in the journal, Science.

The sequenced genome is a template of a normal genome, which could be used to find abnormal genes responsible for diseases. In theory, the template could be used to compare and locate any mutant genes. This could lead to treating and curing diseases (at the genetic level) that have previously been incurable. A map of the human genome could also prevent diseases; genes that predispose individuals to attracting diseases in the future could be identified years in advance.

Out Comes the Genome

The science behind sequencing the human genome has come from a century of discoveries, starting in the late 1800s. At first, genetics was an abstract concept describing hereditary information. Although it was known that hereditary information was passed through generations, the mechanisms were unknown. Once DNA and genes were discovered, the first step to sequencing the human genome was to start with simple organisms, such as, viruses, flies and worms. Then the more complicated human genome could be dealt with. Today, a complete instruction book to make a human being has been identified; however, a complete understanding of the book is still a long way off.

In a way, the human genome is simple in its design, yet incredibly complex in length of code and number of functions. The fundamental unit of the genome is DNA, coded information like letters of the alphabet. Certain sections make up genes; these are like words or sentences. The genes are strung together in chromosomes, which is comparable to chapters in a book. The genome is everything, the whole book. The function of genes is to encode for making proteins. Therefore, genes encode messages (carried by a messenger molecule called RNA) to build proteins. The proteins perform the actual tasks encoded by the genes.

Here are some interesting features of the human genome:

  •  It contains over 3 billion letters of DNA code.
  • The DNA code is written in a 4 letter alphabet (AGCT), named after the initials of the 4 basic chemical units of DNA. If it were in book form, it would take more than 1.5 million pages to write it.
  • The structure of DNA is arranged in base pairs, strands that are connected like a spiral staircase (the double helix).
  • The total number of genes is about 20,687.
  • The genome divided in 23 pairs of chromosomes, 46 in total.
  • Human complexity arises from gene networks (more so than the number of individual genes). Genes can be turned on or off in specific situations, and work in different combinations to produce near-infinite functions.
  • Genes only make up a tiny portion of the genome (only 2%). Most of the DNA either regulates genes, has unknown functions or does nothing at all (junk DNA).
  • Part of our evolutionary past is carried in the genome, fragments of DNA that no longer serve a purpose. They are relics of DNA from ancient organisms that have gone dormant over time. These fragments vastly outnumber genes.
  • Human beings are 99.9% identical at the DNA level (a discrepancy of 1 letter in every 1,200 letters).

References: Siddhartha Mukherjee, The Gene (New York: Simon & Schuster, (2016).

DNA – Episode 3 of 5 – The Human Race – PBS Documentary, published on Mar 21, 2013. https://www.youtube.com/watch?v=MJu9dL7a3ZI


 

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Evolution in a Deck of Cards

dnaFor some people the process of evolution is a difficult concept to grasp. For sure, evolution is a counter-intuitive idea. We don’t experience evolution in our daily lives. It only makes sense when we look beyond the surface of things; evolutionary concepts require a long-term view. Perhaps the biggest stumbling block towards understanding evolution is the disconnection between our lives and the evolutionary timeline. If we compared the history of the Earth to the length of a person’s arm, all of human history could be wiped out with a single stroke of a nail file.

Still, despite much scientific evidence for evolution, many people are not convinced. They may look for supernatural explanations for the existence of life, or conclude the question is beyond human understanding. How is it possible that all life evolved from single cell organisms? How did even a single cell evolve? And how did life diversify into millions of species? To get a grasp for evolution we need to shift our attention from the finished product to the process.

Evolution is indeed a process, which is ongoing. And it has no finished product in mind. Evolution can be defined as gradual changes and development over time. However, there is a mechanism that generates those changes, which Darwin called natural selection. Perhaps Darwin’s greatest insight was recognizing the power of natural selection. It is similar to an algorithm, because nature selects positive survival and reproductive traits. It also discards negative survival and reproductive traits. The process is cumulative and continuous from generation to generation. Once the process began improvements to life were inevitable, even though specific outcomes were not guaranteed.

The Card Game

deck-of-cardsAs a thought experiment we can use the analogy of a card game to show how natural selection works. The analogy is not perfect, because there are subtleties in evolution that are complicated. The exercise is meant to provide a simple analogy for natural selection.

Although it was not known in Darwin’s time, we now understand that life is controlled by genetic information. Essentially, it is genes that are passed on through the generations. In our analogy it is more useful to view the cards as genes, and a hand of cards as a group of genes (or an individual life form). The game has 4 basic ground rules:

1) The deck of cards represents the gene pool: We need to assume multiple decks, because the same genes exist simultaneously in other individuals and are copied many times over. Each card carries information, which may or may not survive each reshuffling. For example, the 5 of spades is one gene and the 10 of harts is another gene.

2) The shuffling symbolizes the generations: Every time the cards are shuffled and handed out, it’s like a new generation. The cards are always being rearranged in different combinations.

3) The players act as natural environments: The players select which cards they want to keep. Just like nature favors different genes in different environments, each player will select different card combinations. In our game some players are playing poker, others cribbage and others bridge. Therefore, the poker player represents a specific environment, such as an ocean.

4) The goal of the game is to collect the best hand possible: Every player keeps the cards they want, and discards the ones they don’t want. The poker players will collect different card arrangements than the bridge players. But all the cards come from the same card pool. This selection process is done with every deal.

Stable Arrangements

For natural selection to work the process had to work in the primordial period. The creation of life on earth probably did not start in an instant of time. It is more likely that the building blocks (atoms and molecules) were assembling for a long time; nature was favoring stable patterns. Richard Dawkins points out in The Selfish Gene:

“The earliest form of natural selection was simply a selection of stable forms and a rejection of unstable ones.”

microscopic-lifeJust like today, things that last are stable arrangements of atoms (whether living or nonliving). Consequently, life began in a fuzzy period where forms were interacting and assembling. At some point the forms acquired the ability to replicate (with occasional errors). The errors are necessary for evolution; this would be like randomly adding new cards to the deck (like a 15 of diamonds). Eventually, simplicity grew into increased complexity; small patterns grew into larger patterns. This is also what happens with the game of cards.

Exact patterns would be difficult to recognize in the first few hands. Nevertheless, there would still be cards that are more desirable than others. Generally, an ace or a face card is better than a numbered card. But there are exceptions, which depends on the type of game and the combination of cards. With each reshuffling patterns will emerge, where eventually an onlooker could identify the game each player is playing. This is analogous to the time when stable patterns would be recognized and classified as organic life (that’s if someone where watching).

Reshuffling the Deck

We can now see how the process of reshuffling the deck, selecting and discarding the cards would work. It would not take too many hands to achieve almost perfection. Each player would select for their specific game, just like nature selects for its specific environment. All the hands would contain some of the same cards, but in different combinations. Nature mixes the genes in the same way.

cards-in-rowsThe power of natural selection is the continual selection and discarding process, which occurs at unfathomable timescales. Successful genes are kept from generation to generation, random gene mutations are added, and remixed in endless combinations. Only the best of the best survive the process. That is why an after-the-fact view of evolution can be deceiving. Incredible order can emerge without a design and a planned outcome.

Our card game never ends; the players are always looking to make improvements, no matter how small. Many poker players will end up with a Royal Flush (the best possible hand). Bridge hands will end up with every card of the same suit or all aces and face cards. This is where our analogy doesn’t quite measure up. In real life the environments constantly change, which drives evolution to adjust. It’s like occasionally changing some rules to each card game, which will force the players to change their hands.

I hope this thought experiment helps to conceptualize how evolution can accomplish a seemingly daunting task. The basics of natural selection are only a starting point towards understanding evolution. Evolution is a messy process of trial and error, an incalculable amount of trials and errors, which muddies the water. Yet the time involved is critical to the process (more than 3 billion years).

Knowledge of evolution is fundamental towards understanding all life on earth. The life sciences could not progress without it. Our own bodies function as a result of evolution and much of human behavior has evolutionary roots. It has been said that, “Evolution is not something you believe in; either you understand it, or you don’t.”

 

References: Richard Dawkins, The Selfish Gene (Oxford: Oxford University Press, First published 1976, Second edition 1989, 30th anniversary edition 2006).


 

Memes that Make the World

dnaMemes are the cultural equivalence of biological genes. The term meme was coined by Richard Dawkins in the 1976 publication of The Selfish Gene. The premise behind The Selfish Gene is that Darwinian natural selection acts at the level of genes; ultimately, it is genes that guide evolution by controlling the traits in bodies that contain the genes. In order for natural selection to work, there needs to be something like DNA and genes in which information is replicated. There also requires some copying errors so that small variations can occur from one generation to the next. Memes also fit that description.  Memes are ideas that survive in human brains, and similar to genes they can be copied and passed on.

There are many different types of memes: for example, songs, hairstyles, phrases, beliefs, words and manners. In today’s world the word meme has become popular on the internet. Whenever we here that something has “gone viral,” it is often referred to as a meme. In most cases the meme is something trivial, such as a piece of music, a surprising story or a silly video. It spreads rapidly, but usually it will not last very long. However, other memes have a far greater impact on society, and become part of cultural evolution. Or you could say that the memes guide cultural evolution, much like “the selfish genes.”

The Meme Codes

Language may be the key ingredient that allows memes to spread. Like a DNA code, language is also coded information. It comes in the form of letters and words. Speech is one variation of language, which is surely copied, but written language is even more stable as a replicating code.

We can all recall numerous instances when an event is passed from one story-teller to another. In most cases the details in the story changes until we have conflicting accounts. The information is transferred from one individual brain to another, but memories are not perfect and the copies are not exact. However, written language can exchange hands without the story being altered. The stories still have to resonate in people’s brains and the interpretations will vary, but the fidelity of the written word is higher than the spoken word.

Music is another meme that has two routes of transition. 1) Tunes are passed on by hearing the sounds and attempting to duplicate them. If a tune sounds appealing there is a higher chance it will be copied. As time passes the tune will change a bit. 2) Music can also be written in sheet music using mostly symbols. Like written language, the written music will remain close to the original form. One piano player following a sheet music may sound slightly different from another player. But as the song is played by many piano players it will not change significantly.

MathematicsMathematics is a meme of numbers, symbols and diagrams. It is more accurately copied than language, because there is less ways it can be altered. 2 plus 2 will always equal 4. There is an order in mathematics that is self-correcting, although concepts evolve over time with new applications. Language, music and mathematics are coded information that are replicated and evolve in human brains.

Marching on Through the Generations

The idea of generations is different for memes than it is for genes. A different generation for a gene is an offspring, which will carry some of the same genes. For memes, there is a double meaning for a generation. A meme can be passed on from person to person in a single day, or survive for many years. For instance, I tell you an idea, and you share it with someone else. That’s 3 generations, from me to you to someone else. In this scenario the meme could evolve like microbes, where mutations can occur in a matter of days or weeks. The idea will spread quickly, but each person could add to it or leaves something out; these would be mutations of the original idea.

There are also memes that are handed down in the traditional sense of generations, that is, from a father to a son. These memes are long-lasting and could become cultural norms or traditions. For example, holidays are memes that have survived for many years. In many cases the original customs and purposes behind the holidays are lost or changed (at least by some people). Still the celebrations continue and millions of people observe the holidays. Do we know why the colors of Christmas are red and green, or why the Easter Bunny gives out eggs, or why children get candies at Halloween?

Memes Working Together

Similar to a single gene, a single meme has a minor impact. Genes are effective when they combine with other cooperative genes. Memes also combine with compatible memes and also compete with other memes for attention in human brains. One could think of different ideas as a meme pool, which people select (consciously or subconsciously). The memes that work well together will be more likely to be copied. A meme-complex could be copied because it benefits society, but it could also be copied because it aids the propagation of itself. It is not a guarantee that humans will make the best possible choices; there are equal reasons to believe that we will choose unwisely.

football stadiumA sport is an example of a well-established meme-complex. The North American culture is fascinated with sports on a daily basis. Many play sports at local venues; many more watch sports at stadiums and on televisions. What memes could be working together? How about this list: (memes for running, throwing and catching), (memes for competing, winning and losing), (memes for watching, cheering and analyzing). Any stable and self-replicating cultural norm will consist of mutually beneficial memes.

History-Making Memes

Recorded human history is a story of culture. The ideas that populations believed in mass, whether real or imagined, has fueled the events of history. The most influential ideas (memes) have won out over other ideas. Not always because they were better ideas, but because they were more effective at spreading from brain to brain. Historian Yuval Harari writes in Sapiens: A Brief History of Humankind:

… history’s choices are not made for the benefit of humans… There is no proof that cultures that are beneficial to humans must inexorably succeed and spread, while less beneficial cultures disappear.

Religion symbolsThe cultural enterprises that have dominated human life contain large numbers of memes. Such examples are: religion, war, agriculture, kingdoms, art, music, politics, nationalism and science. No one can tell if the history-making memes (or meme-complexes) took the best course of action for humanity. Some did and others did not. Nevertheless, they had the attributes to enter human brains and to be imitated. Our modern culture is formed by memes with the same qualities as the historical memes. That is, copying fidelity, with variation, and wide-spread selection from the meme pool.

 

References: Yuval Noah Harari, Sapiens: A Brief History of Humankind (Canada: Signal Books, an imprint of McClelland & Stewart, 2014).

Richard Dawkins, The Selfish Gene (Oxford: Oxford University Press, 30th anniversary edition, 2006).

Richard Dawkins | Memes | Oxford Union, Published on Feb. 26, 2014. 

Susan Blackmore sobre memes e “temes” – TED Legendado, Published on Jul. 13, 2013.