Uworld Bio- Genetics and Evolution (esidahi)

Hardy- Weinburg assumptions

- No new mutations - No natural selections - No gene flow in and out - Random mating - Large population size When a population is in Hardy-Weinberg equilibrium, - allelic frequencies do not change from one generation to another. - As such, heterozygosity in Hardy-Weinberg equilibrium is neither decreased nor increased but remains the same over time.

Kidney function

1) Control of extracellular fluid volume & regulation of blood pressure via the renin-angiotensin system 2) Regulation of osmolarity (ie, excretion or retention of water) 3) Regulation of ion concentration (Na+, K+, Ca2+) by balancing dietary ion intake with urinary excretion 4) Regulation of pH via bicarbonate buffer system (excretion/retention of HCO3− and H+) 5) Excretion of waste (creatinine, ammonia, urea, foreign substances) 6) Production of renin (enzyme involved in blood pressure regulation) & hormones (erythropoietin for erythrocyte production & calcitriol for increased Ca2+ levels)

nonsense mutation

A nonsense mutation - is a point mutation in which a single nucleotide change creates a premature stop codon, causing early translation termination and production of a truncated (shortened) protein.

Adaptive radiation = aka Darwin's finches - different beaks for different functions

Adaptive radiation - is the process of diversifying characteristics in a subgroup of individuals from a single species. - It reduces intraspecific competition, the competition for resources by members of a single species. As a result, fitness is improved for the entire species because the subgroup has a new role within an ecological community (niche) that is different from the rest of the species. - Adaptive radiation can eventually lead to speciation, or the formation of a new species, if the subgroup continues to diverge. - and loses the ability to interbreed with individuals from the original species.

Autosomal recessive conditions

Autosomal recessive conditions Father - A a (affected) Mother - A a - require the presence of two copies of the defective gene for disease manifestation and show no predilection for males or females. - About 25% (aa) of children are affected if both parents carry one copy of the defective gene (most common scenario).

Autosomal traits

Autosomal traits - arise due to the expression of alleles present on an organism's autosomes. - These alleles are passed to offspring through inheritance of the parental autosomes. Because males and females all have the same number of autosomes, autosomal traits are generally expressed in the same proportions in males as in females.

Bottlenecks = Not by chance

Bottlenecks - is the drastic reduction in population size that occurs in response to some sudden and uncontrollable disaster - due to environmental events (eg, flood, famine, human-induced catastrophe) or human action (human-induced catastrophe) - greatly reduce the genetic diversity of a population. Consequently, a smaller population has a reduced ability to buffer the negative impacts of random changes in allele frequencies (genetic drift) that may result in extinction.

Codominance

Codominance - describes the co-expression of alleles as observed in the phenotype of heterozygous individuals. In the case of codominant traits, neither allele is fully dominant or fully recessive. Common examples of codominance include the co-expression of both red (R) and white (W) alleles in a speckled offspring (RW). In this example, in vitro studies suggest that both wild-type and mutant TLRs are observable by protein electrophoresis. This phenotype can be attributed to the co-expression of the normally functioning receptor and the mutated receptor, or the codominance of tlr4(+) and tlr4(d) alleles.

recombinants

Crossing over can produce new combinations of alleles within a chromosome by moving some alleles of the maternal copy to the paternal copy and vice versa. New combinations of alleles are called - recombinant, whereas combinations that already existed in the parent are called - parental.

Diff btw Crossover and alternative splicing Crossover events = leads to genetic diversity Alternative splicing = leads to protein diversity

Crossover events result in daughter cells with chromosomes containing combinations of alleles that differ from those in the parent cell, leading to eukaryotic genetic recombination and increased genetic diversity. Because crossover events produce genetically unique gametes, the offspring that develops after fertilization is genetically different from either parent and more genetically diverse. In alternative splicing, a single gene transcript is processed to produce various mRNA molecules that encode different proteins, depending on the inclusion or exclusion of particular exons. Alternative splicing can increase protein diversity, but it does not increase genetic diversity as the genetic makeup of an offspring is not altered.

Disruptive selection = both extremes

Disruptive selection - results in the selection of 2 extreme phenotypes that differ from the average. - the average phenotype is selected against while 2 extreme phenotypes are selected for.

Who can pass through?

Due to their charged nature, ions cannot freely cross the plasma membrane because the membrane contains a middle layer of uncharged fatty acid chains. Consequently, an ion must pass through the pore of an ion channel to enter the cell. Ion channels are transmembrane protein complexes that fluctuate between an open or closed conformation to facilitate ion transport. These channels exhibit selectivity as only specific ions may pass through the pore and down their concentration gradient (high to low). For a particular ion to go through a channel, the inside of the channel's pore must be lined by amino acid residues with charges opposite to the ion's charge. This is because oppositely charged species attract each other whereas identically charged species repel each other. In addition, the ion must be briefly pulled out of its hydration shell to pass from the aqueous environment outside the plasma membrane to the aqueous environment inside the cell. The opposite charges within the pore stabilize the charge of the newly dehydrated ion. Per the passage, PC2 forms a mechanically activated Ca2+ channel. For positively charged Ca2+ to pass, the inside of the pore must be lined by amino acid residues that are negatively charged at physiological pH. Aspartate (D) and glutamate (E) are the only amino acids that fit this criterion. Arginine (R) and lysine (K) are both positively charged and would therefore repel positively charged Ca2+.

Convergent, Divergent and Parallel evolution

Educational objective: Convergent evolution - leads to similar characteristics in distantly related species that are exposed to similar environmental pressures. Parallel evolution - occurs when two more closely related species (ie, descended from a more recent common ancestor) continue to evolve the same characteristics to adapt to similar environments. Divergent evolution - occurs when two species descended from a recent common ancestor inhabit contrasting environments and evolve distinct characteristics that allow them to better adapt to their differing environmental pressures.

Genetic linkage

Educational objective: Genetic linkage refers to the tendency of alleles in close proximity to remain on the same chromosome and be inherited together by offspring. This tendency occurs because of fewer crossover events between these loci during meiosis, resulting in a greater number of haploid gametes with nonrecombinant genotypes.

Hardy-Weinberg equations

Educational objective: Hardy-Weinberg equations can be used to relate allele frequencies and genotype frequencies. Genotype frequencies are equal to the probability of inheriting each genotype, with the frequency of homozygotes equal to p2 or q2 and the frequency of heterozygotes equal to 2pq. p + q = 1: If two versions (alleles) exist for a given gene, respective allele frequencies are commonly denoted as p, which represents the major (most common) allele, and q, which represents the minor (less common) allele. Statistically, the sum of these frequencies must equal 1. p2 + 2pq + q2 = 1: Genotype frequency can be determined by the probability of inheriting a genotype and is therefore dependent on allele frequencies. The frequency of homozygotes is equal to p2 or q2 whereas the frequency of heterozygotes is equal to 2pq.

crossing over aka genetic recombination

Educational objective: In eukaryotes, genetic recombination occurs via crossover events (exchange of DNA segments between homologous chromosomes). Synapsis or the joining of homologous chromosomes into tetrads occurs during prophase I of meiosis and is required for crossing over to occur. Crossovers increase genetic diversity by mixing maternal and paternal alleles into a single chromosome that is then inherited by the offspring.

Ion channels

Educational objective: Ion channels allow charged atoms to pass between the extracellular and intracellular environments down their concentration gradient. The charge of the amino acids that line the inside of the channel's pore plays a key role in determining which ion can pass through.

Survival curves

Educational objective: Survival curves plot percent survival against an independent variable, usually time or dosage. Survival curves can be used to determine LD50, defined as the minimum dose causing death in 50% of test subjects.

RBC and WBC

Erythropoietin production: The adult kidneys normally produce erythropoietin, a hormone that signals the bone marrow to increase red blood cell (erythrocyte) production. Generation of erythropoietin would be impaired in ESRD Leukocytes production (white blood cells) occurs in the bone marrow, not the kidneys. Leukocytes are immune system cells that protect the body against infectious agents and foreign antigens. Consequently, leukocyte numbers are regulated by the presence or absence of cytokines released during active infection. Educational objective: The kidneys' primary function is to maintain the salt and water balance of the blood. They also play a key role in regulating multiple aspects of physiological homeostasis (eg, blood pressure, waste removal, osmolarity, blood pH, erythrocyte production).

Inbreeding → ↓heterozygosity → ↓reproductive success, and ultimately → extinction or the elimination of the species.

Fitness is reduced in inbreeding populations because - inbred offspring have an increased probability of being homozygous for deleterious recessive traits due to the low genetic diversity between their parents. Individuals with low genetic diversity in MHC alleles have low fitness because it reduces their ability to fight novel diseases and pathogens. Therefore, repeated generational inbreeding within the cheetah population will lead to decreased heterozygosity, reduced reproductive success, and ultimately extinction or the elimination of the species.

Frameshift mutations

Frameshift mutations - result from the insertion or deletion of a number of nucleotides not divisible by three. These mutations change the reading frame of the transcript, giving rise to proteins with altered amino acid sequences

Gene flow,

Gene flow, - due to migration, - increases genetic diversity by introducing new alleles to the gene pool. Therefore, small populations with low genetic diversity are more likely to benefit from gene flow and therefore are less likely to go extinct.

Genetic drift = chance event

Genetic drift - due to random genetic changes that are not related to natural selection - (eg, sampling error, chance event). - Although all populations are affected by genetic drift, its effects are more significant in --> smaller populations because they have a reduced gene pool. The smaller gene pool cannot buffer random (good or bad) variations in allele frequencies that occur due to chance events. In other words, the probability of a beneficial allele being removed by genetic drift increases for populations whose genetic diversity is low. Similarly, drift increases the probability of a deleterious allele becoming fixed within the population.

If two genes are located close together on a chromosome = fewer progeny with recombinant combinations than parental combinations.

If two genes are located close together on a chromosome (measured in centimorgans, or map units), - they are relatively unlikely to be separated by a recombination event. This is because there is less distance between the two genes in which a recombination can occur. Therefore, substantially fewer progeny will have recombinant combinations than parental combinations. - As a result, the recombinant progeny can be identified by the fact that there are fewer of them. Table 1 shows that only 43 of 500 flies (~9%) were recombinant. Given this small percentage of recombinant flies, it is likely that the PTP and Abl genes are close together on the chromosome.

How does the body respond to stress?

In response to stress, - the hypothalamus stimulates the pituitary gland to release (ACTH). - As a result of ACTH release, the adrenal cortex secretes glucocorticoid hormones such as cortisol. - Cortisol mediates stress responses by increasing blood glucose levels and decreasing inflammation and protein synthesis. Chronic exposure to cortisol can negatively impact immunologic responses, increase the susceptibility for diseases, and affect reproductive health (fecundity).

stabilizing selection = average

In stabilizing selection, - phenotypes are narrowed toward an average, homogeneous phenotype by selecting against extreme phenotypes; - as a consequence, diversity is decreased within the population.

Anaphase I and II

In the absence of recombination, maternal and paternal alleles are separated from each other during anaphase I, and identical alleles on each sister chromatid are separated from each other - (pulled to opp poles by the mitotic spindle ) during anaphase II. Mitosis Ana-Sister chromatids separate (diploid Anaphase I - Homo Chromosomes separate Ana II-Sister chromatids separate (haploid)

Incomplete dominance

Incomplete dominance - between alleles results in a blended or intermediate phenotype observed in heterozygous individuals. A common example is pink color (Rw) in offspring produced from a cross between red flowers (RR) and white flowers (ww). Similarly, quantitative data indicate that the heterozygous F1 generation [tlr4(+)/tlr4(d)] has an intermediate immune response to LPS when compared to He-N mice [tlr4(+)/tlr4(+)] and He-J mice [tlr4(d)/tlr4(d)] mice. This result could be attributed to incomplete dominance.

Major Histocompatibility Complex (MHC)

MHC alleles - encode surface receptors on all nucleated cells that play a role in the activation of the adaptive immune system. Typically, increased MHC variation - enhances an organism's ability to combat a variety of infections and diseases. - As a result, it is associated with increased fitness

Erythrocytes (RBC) contain no mitochondria - As a result, mitochondrial mutations do not affect erythrocytes.

Mature red blood cells (RBCs), or erythrocytes, - mainly contain hemoglobin, - RBCs are highly efficient transporters of oxygen as they expel their nucleus and other organelles during synthesis (erythropoiesis) in the bone marrow to maximize the available space for hemoglobin. As a result, RBCs contain *no mitochondria* and so, *mitochondrial mutations cannot affect erythrocyte function*. RBCs never consume the oxygen they are transporting as they produce energy only via anaerobic glycolysis, an oxygen-independent metabolic pathway that is less efficient than the aerobic one.

Metaphase I and II

Metaphase is the phase in which chromosomes align in the middle of the cell on the metaphase plate. Mitosis Meta-Sister chromatids align (diploid) Metaphase I - Homo Chromosomes align Metaphase II - Sister chromatids align (haploid)

mitochondrial DNA - inherited in a maternal fashion (ie, no paternal contribution). Mitochondria within sperm are not transferred into the ovum during fertilization; therefore, males never pass on their mitochondria.

Mitochondria - have their own genome; (DNA) Their main functions include - ATP generation, - heat production, and - beta-oxidation of fatty acids. Mitochondrial genes are extranuclear and inherited in a distinctly different manner than nuclear genes (autosomal and sex-linked). During fertilization, mitochondria within sperm do not pass into the ovum; therefore, - - only maternal mitochondria are transmitted to the fetus. Only affected females transmit abnormal mitochondria to offspring; transmission never occurs through males, even if they are affected. - As a result, only affected mothers with the mtDNA A3243G mutation can pass it on to their offspring.

Diff btw Mit and Mei

Mitosis is the process by which a cell divides to create two genetically identical daughter cells. However, during mitosis, homologous chromosomes do not pair up into tetrads and crossing over does not occur.

Natural selection

Natural selection - is an evolutionary mechanism by which only beneficial alleles are selected for while unfavorable traits are selected against. These selected changes alter the population's allele frequencies, which improves the species' fitness. Consequently, these populations have an improved probability for survival rather than an increased probability for extinction.

Penetrance

Penetrance - is defined as the proportion of individuals with a genotype who express the corresponding phenotype. complete penetrance When every individual with a specific genotype displays the associated phenotype incomplete penetrance When all individuals have the same genotype but only some express the corresponding phenotype - (eg, not all patients with the A3243G mtDNA mutation exhibit hearing loss

Random mating

Random mating - increases a population's genetic diversity because of the inherent variations that arise during meiosis (recombination) and sexual reproduction (fusion of gametes). Therefore, the variations or changes to the allele frequencies due to random mating will primarily be beneficial to a population as a whole.

Sex-linked traits

Sex-linked traits - arise due to the expression of alleles present on an organism's sex chromosomes. Because the X chromosome contains significantly more genes than the Y chromosome, the majority of sex-linked traits are linked to the X chromosome. - Due to sex determination, male offspring (XY) receive their X chromosome from their mother (XX) and their Y chromosome from their father (XY). - Because males have only one X chromosome and cannot compensate with another, males in a population generally express recessive X-linked traits in higher proportions than their female counterparts.

Types of DNA Mutations

Silent - Single base pair change that does not change the amino acid sequence Missense - Single base pair change that gives rise to a new amino acid Nonsense - Single base pair change that gives rise to a stop codon Insertion - Addition of one or more base pairs into the DNA sequence Deletion - Removal of one or more base pairs from the DNA sequence Duplication - Incorporation of one or more copies of a portion of the DNA sequence Frameshift - Addition or removal of a number of base pairs that is not a multiple of three, resulting in a new reading frame Repeat Expansion - Incorporation of multiple copies of a short base pair sequence in a row

Speciation = New species

Speciation - is the evolutionary process of forming a new species from a previously existing species. This process occurs over many generations and results in organisms that cannot interbreed with the ancestral species. Although the subgroup of cheetahs developed different characteristics, it retained the ability to mate with Namibian cheetahs and is therefore not considered a separate species.

Immune Defense=innate and adaptive immune systems

The innate immune system - consists of cells poised to attack antigens in a nonspecific manner. These cells include macrophages, dendritic cells, natural killer cells, and granulocytes. This system responds to foreign antigens within minutes to hours and can recognize unique and common motifs present on pathogens. The adaptive immune system - contributes specialized or acquired immunity based on learned recognition of specific antigens. Responses of adaptive immune system can be further subdivided into cell-mediated and humoral immunity: In cell-mediated immunity, - mainly driven by T cells, receptors on immune cells recognize and bind directly to receptors on target cells. In humoral immunity, - B cells produce antibodies specific to a new antigen (primary immune response). These antibodies enable the immune system to respond more quickly if the antigen is encountered later (secondary immune response).

Variable expressivity

Variable expressivity - refers to the ability of a single genotype to give rise to multiple phenotypes. In the context of disease, two patients with the same mutated allele may exhibit markedly different clinical symptoms. T - individuals with the mutation exhibit variable phenotypes such as mild to severe degrees of hearing loss

X-linked dominant condition

X-linked dominant condition Father - X° Y (affected) Mother - X X - All daughters are affected - All sons are normal Father - X Y Mother - X X° (affected) - All sons and daughters have 50% chance of being affected - Only one copy of the dominant allele of the gene is necessary to inherit an X-linked dominant condition. - These diseases are characterized by a lack of father-son transmission, but all daughters of an affected father are affected. - Affected mothers have a 50% probability of having an affected child.

X-linked recessive conditions

X-linked recessive conditions Father - X° Y (affected) Mother - X X - All daughters are affected - All sons are normal Father - X Y Mother - X X° (carrier) - daughters have 50% chance of being carriers - sons have 50% chance of being affected - Affected males have asymptomatic carrier mothers in X-linked recessive conditions, which are inherited via the X chromosome. Two mutant alleles must be inherited to cause disease in females (XX), but only one mutant allele is required to cause the disease in males (XY).

Directional selection = one extreme preferred

directional selection, - one extreme phenotype is favored over all other phenotypes because of the additional fitness it confers. Consequently, the frequency of the related allele increases dramatically within a population.

substitution

substitution - is either a silent or a missense mutation, silent - the nucleotide change corresponds to the same amino acid as in the original sequence missense - the nucleotide change corresponds to a different amino acid